Oral Communications

OC-1

CHAIRS:
Liliana Cancela
Gaston Calfa
Ricardo Pautassi

ZOOM LINK

María Angélica Benítez

Laboratorio Interdisciplinario de Neurociencia Cognitiva (LINC), Centro de Estudios Multidisciplinario en Sistemas Complejos y Ciencias del Cerebro (CEMSC3), Instituto de Ciencias Físicas (ICIFI), Escuela de Ciencia y Tecnología (ECyT), Universidad de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

Memory and musical training in adolescents

The relationship between musical experience as well as general cognitive development throughout life has been widely studied. Studies have found that musicians achieved higher scores in memory tasks than non-musicians, but this was not investigated in the performance of emotional memory in adolescents’ musicians and non-musicians. The goal of this study was to evaluate the relationship between musical experience, emotional and neutral memory in a sample of Argentinian adolescents. The performance of 30 adolescents between 12 and 15 years old, trained in Argentinian Conservatories of Music was compared to adolescents without this type of training in an emotional and neutral memory task (based on the International Affective Pictures System). They were evaluated on their free recall and recognition of the images, both immediately and deferred. The evaluations were carried out remotely due to publicly known sanitary restrictions. The results showed that the emotional material was more remembered than the neutral one. Immediately, no significant differences were found between the groups, however, it was found that the musicians remembered a greater number of images than the adolescents without musical training in the deferred measures (both neutral and emotional). Lastly, no significant differences were found in the recognition tasks. The results, of social, clinical, and educational implication, show that musical training modulates the emotional and neutral memory of adolescents.

Martina Boscolo

Laboratorio de Neurociencia, Universidad Torcuato Di Tella

Can video games enhance children and adolescents' cognitive capabilities? A systematic review of the transfer of video game training to cognitive and psychosocial abilities

Video games are extremely popular, especially among adolescents. Even though the effects they have on cognitive and psychosocial aspects have been widely studied, there is no consensus in the literature on the predominance of their beneficial or negative effects on children and adolescents’ cognition. Evidence on this could shed some clarity on the potential of video games as educational resources to stimulate cognitive development. We conducted a revision on the effects that playing video games has on cognition in people under the age of 18, and considered its transfer to other aspects of life. After extensive search and filtering processes, 34 experimental and correlational studies were analysed. We found that certain video games positively affect executive functions, attention, memory, and decision making, among other cognitive capabilities. On the contrary, other video games are related to an increase in aggressiveness and risk-taking behavior and to a decrease in prosocial behavior. Moreover, various video games that have these effects are very popular and emerge as some of the most-downloaded and most-played nowadays. Given that playing video games might trigger experience-dependent plasticity, it is necessary to understand to which extent they affect cognitive development in ecological settings. This revision allows for a better comprehension of this research field. Key words: Video games, Cognition, Adolescence, Childhood, Transfer

Julio Roberto Castillo Elias

Laboratorio de Neurogénesis Adulta, Departamento de Fisica Médica, CNEA

A population dynamics model about how learning promotes adult neurogenesis in delimited regions of the zebrafish pallium.

Neural stem cells (NSCs) in the zebrafish pallium undergo through both symmetric and asymmetric divisions in order to generate new-born neurons and to perpetuate the NSC reservoir pool. A few studies address how the activity of neural circuits regulates the adult neurogenesis homeostasis, while the role of cognitive activity on new-born neuronal addition has not been explored yet. Here we aimed to test whether cognitive activity enhances adult neurogenesis by training zebrafish in a spatial relational task. We found that learning increases a ~3 fold NSC proliferation in the rostral-dorsomedial (rDm) pallium, when compared to mocked controls. Next we evaluated the role of learning on neuronal addition in the pallium. To do this, a cohort of proliferating NSCs were labeled by BrdU administration, and then fish were trained during 2 or 3 consecutive weeks. We found that training increases the number of newborn neurons in rDm proportional to the extent of cognitive activity. To understand the cellular mechanisms behind these results, we developed a population dynamic model of proliferating NSCs (based on Than-Trong el al 2020), where NSC proliferation and death are sensitive to cognitive activity. Our model suggests that learning in a spatial relational task promotes neurogenesis in rDm in two ways: firstly, by promoting newborn neurons’ rescue from apoptosis due to network activity, and secondly, by acting as a catalyst for a successive labeled-NSCs proliferation.

Nicolás Comay

Cognitive Science Group - Instituto de Investigaciones Psicológicas (IIPsi - CONICET - UNC)

Implausible alternatives paradoxically increase confidence in a perceptual decision

Computational models of confidence in perceptual decisions predict that the presence of implausible alternatives in a decision making task should not affect reported confidence. However, research in non-perceptual tasks showed that implausible alternatives increase confidence, a counterintuitive finding that defies current understanding of confidence processes. Here we experimentally test whether this phenomenon also plays a role in perceptual decision making. We conducted 3 online experiments. In experiment 1 and 2 participants had to decide which of a set of stimuli was the biggest, and report their confidence level. In Exp1 half of the trials included very small, clearly incorrect stimuli, whereas in Exp2 one to three small alternatives were added. We found that the addition of implausible alternatives increased confidence. Moreover, confidence increased monotonically with the number of weak alternatives. In experiment 3 we aimed to replicate our findings in a different task; here confidence only increased minimally in correct trials. These results are hardly compatible with current computational models of confidence. Therefore, we proposed one alternative model that accounts for our data. Our work contributes to a thorough understanding of the cognitive processes underlying our sense of confidence, and proposes venues for future research.

Alvaro Concha Alvarez Prado

Neurobiology of Movement Lab, Medical Physics Dept, Instituto Balseiro, UNCUYO-CNEA

What can non-linear embeddings tell us about the way a mouse learns a motor skill?

Animals exhibit complex behavioral repertoires that can be described as combinations from a finite set of stereotyped movements. Behavioral responses are flexible, since different movement sequences can be used to solve similar tasks, and are adaptable to changing environments through learning mechanisms. Given its adaptability and flexibility, translating animal behavior into quantifiable movement sequences can be challenging. On the one hand, manual classification can be time-consuming and not reproducible between subjects. On the other hand, heuristically created categories tend to ignore inherent information regarding intra- and inter-animal variability, frequently found in unrestrained behavior. In addition, a quantitative description of animal behavior is required to understand how the brain encodes particular behaviors, what are the underlying neural circuits and how these circuits are modified during motor learning. In this work, we used unsupervised machine learning techniques to classify different types of movements executed by mice performing a motor skill learning task (accelerating rotarod). We used UMAP embeddings to find a low dimensional representation of mouse behavior. We then clustered these behaviors into separate categories and associated them with specific movement sequences and learning stages. In this way, we shed light on the underlying structure of animal behavior, improving our understanding of the learning dynamics of a new motor skill.

Ana Belén de Landeta

1 Laboratorio de Memoria, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina 2 Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Assessing the object recognition memory dynamic network upon retrosplenial cortex inactivation- a functional neuroimaging study in rats

Little is known about the object recognition memory (ORM) network. We recently found that the retrosplenial cortex (RSC) is required for ORM consolidation and retrieval; yet RSC inactivation during acquisition prevents its requirement for these memory stages, suggesting that ORM network changes. To assess this we used cerebral blood flow (CBF) SPECT for imaging rats brain activity patterns during habituation (H), training (TR), test (TS, 24h) and re-test (reTS, 7d after TR) in 2 groups; rats infused with saline (control, Ctl) or muscimol (Musc, GABA A agonist, 0.1 µg/side) into the RSC 15min before TR. Within group comparison showed that CBF during TR compared to H decreased over the midline cortical regions from prefrontal cortex to the RSC. Also, CBF increased during TR in the lateral hypothalamus and superior colliculus. During TS compared to TR, CBF increased in the piriform and lateral entorhinal cortex. When compared reTS to TS, CBF decreased in the anterior cingulate cortex and the ventral thalamic nuclei. The deactivation of RSC during TR was stronger in the Musc group, but the largest differences between groups were found during TS. In this condition, CBF in the orbitofrontal cortex and dorsal hippocampus decreased in the Musc group, while CBF in the RSC was higher in this group. We uncovered complex brain-wide activation patterns in the different stages of ORM and showed that RSC inactivation during memory acquisition changed the memory network during retrieval.

Rodrigo Manuel García-Virgolini

Facultad de Psicología; Universidad Nacional de Córdoba

Effects of elevated episodic alcohol consumption during adolescence on recognition memory

Adolescent alcohol consumption is an important health issue in Argentina. Many studies indicate that age of first intoxication is more relevant than age of first contact in explaining alcohol related disorders. This suggests that preclinical studies should focus on models that generate high amounts of consumption in a short time. The present study assessed in male and female Wistar rats the effects of chronic exposure to alcohol during adolescence on recognition memory, with a model simulating elevated episodic alcohol consumption (EEAC). The hypothesis was that exposure to EEAC would result in significant deficits in recognition memory. 48 rats were submitted to a protocol of daily intermittent 2 hour sessions of alcohol auto-administration (EtOH 10%) during adolescence from postnatal days 30-50. Control group received water. Between postnatal days 60-67 rats were evaluated with novel object recognition test. Rats exposed to alcohol during adolescence exhibited significantly less distance traveled in experimental arena [F(1,44)=4.82; p=0.03]. However, no alcohol induced deficits were observed on novel object discrimination. Furthermore, rats that had undergone EEAC showed slight but significant increase in novelty discrimination compared to controls [F(1,44)=4.21; p=0.04]. The hypothesis that EEAC would impair recognition memory was not confirmed. Nonetheless, less distance traveled by animals exposed to EEAC suggests the procedure may have altered motivational patterns.

Candela Sofia Leon

Laboratorio de Sueño y Memoria/Instituto Tecnológico de Buenos Aires

Impairment of aversive episodic memories during Covid-19 pandemic: The impact of emotional context on memory processes

Episodic memory is the ability to recall about what, where and when the event happened. Furthermore, there is a consensus that pleasant or aversive events are better remembered than neutral events and that episodic memory processes are modulated by anxiety and depression. People’s mental health has deteriorated due to the COVID-19 pandemic, showing a growth in anxiety and depressive symptoms. Here, we hypothesize that the increase in negative symptoms modifies the ability to encode and consolidate memories. To study this, we evaluated the effects of emotional context on encoding and consolidation of aversive and neutral episodic memories.

Fernando Gabriel Luna

Instituto de Investigaciones Psicológicas (IIPsi, CONICET-UNC), Facultad de Psicología, Universidad Nacional de Córdoba, Argentina

Dissociated neural mechanisms for executive and arousal vigilance

Vigilance is the challenging ability to sustain attention during long periods. Recently, it has been proposed that vigilance is better understood as two dissociated components: (a) executive vigilance, a cognitive component implied in detecting infrequent critical signals; and (b) arousal vigilance, a rather automatic component involved in sustaining fast responses to stimuli from environment. The present study aimed at dissociating the neural mechanisms of the executive and arousal vigilance components. 37 participants (age: M = 25.86; SD = 4.99) completed two experimental sessions, in which the ANTI-Vea task (i.e., a continuous behavioral task of ~38 min suitable for simultaneously measuring vigilance components) was performed while EEG signal was recorded. Dissociated neural responses were observed for vigilance components. For executive vigilance, correct detections were anticipated by a decline in alpha power prior to the infrequent critical signal appearance. Instead, for arousal vigilance, fastest responses were anticipated by a reduced delta power prior to stimuli appearance. Moreover, while the executive vigilance decrement was observed as a change on late event-related potentials (i.e., P3 and slow positivity), the slowness on arousal vigilance responses was found as a change in P2, a rather earlier event-related potential. Altogether, this study presents a novel dissociation of the neural mechanisms associated with vigilance components.

Malen Daiana Moyano

Laboratorio Sueño y Memoria, Dpto Ciencias de la Vida, ITBA

Non-Linear susceptibility to interferences in declarative memory information

After encoding, memories go through a labile state followed by a stabilization process known as consolidation. Once consolidated they can enter a new labile state after the presentation of a reminder of the original memory, followed by a period of re-stabilization (reconsolidation). During these periods of lability the memory traces can be modified. Currently, there are studies that show a rapid stabilization after 30 min, while others show that stabilization occurs after longer periods (e.g. 6 h). Here we investigate the effect of an interference treatment on declarative memory consolidation, comparing distinct time intervals after acquisition. On day 1, participants learned a list of non- syllable pairs (List 1). Immediately after, 30 min, 3 h or 8 h later, they received an interference list (List 2) that acted as an amnesic agent. On day 2 (48 h after training) participants had to recall List 1 first, followed by List 2. We found that the List 1 memory was susceptible to interference when the List 2 was administered immediately or 3 h after learning; however, shortly after acquisition (e.g. 30 min) the List 1 memory becomes transiently protected against interference. We propose the possibility that this rapid memory protection could be induced by a fast and transient neocortical integration becoming partially independent from the hippocampus followed by a hippocampal re-engagement where the memory becomes susceptible to interferences again.

Ana Paula Toselli

Cátedra de Fisiología Animal - Facultad de Ciencias Exactas, Físicas y Naturales - UNC

Gestational environmental enrichment affects offspring behavior of adolescent rats in a sex specific manner: A preliminary investigation

The maternal environment is important for embryonic brain development. We investigated whether environmental enrichment during the gestation period influences offspring behaviors in juvenile male and female rats. Pregnant rats (from gestation day 1 to 20) were housed in an enriched environment (EE) consisting of large cages for exploration, stimulating toys, running wheels and eight companions for social interaction. A control group was housed in standard cages (two per cage). After birth, litters from both groups were maintained in a standard environment until 45 postnatal day. The effects of maternal enrichment on the behavior of male and female offspring were determined by elevated plus maze (EPM), open-field (OF) and social preference test (SPT). The results showed that in EPM, female offspring of EE mothers spent more percentage of time in open arms indicating a decrease in anxiety-like behavior. In OF, male and female EE rats showed more locomotor activity and spent more time in the aversive inner zone of the maze than control rats, indicating lower emotional reactivity behavior. When examining social behavior, there is a preference for investigating the social stimulus over the object stimulus in all groups. However, EE males exhibit less time spent investigating the social stimulus compared to control males. The evidence demonstrates that maternal exposure to EE affects the behavioral trajectories of offspring in a sex-specific manner.

OC-2

CHAIRS:
Marta Antonelli
Macarena Fernandez
Ines Samengo

ZOOM LINK

Camila Coll

Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO)

Can Tourette syndrome phenotypes be induced by acutely inhibiting Nkx2.1 derived striatal interneurons?

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Most patients also present comorbid conditions like OCD and ADHD. TS pathophysiology remains poorly understood, however, the number of PV+, nNOS+ and ChAT+ striatal interneurons (SIs), which all derive from cell precursors expressing the transcription factor Nkx2.1, is reduced in the brain of TS patients. In previous studies, where we achieved a combined ablation of SIs, lesioned mice developed abnormal involuntary movements resembling motor tics and also behaviors reminiscent of common comorbid conditions, including an increase in stereotypies, locomotion, and spontaneous repetitive behaviors. Nonetheless, ablations give time for plastic compensations to occur, which brings to the question, can these phenotypes be induced by acutely inhibiting the SIs, or only after an ablation? To get a transient inhibition of the SIs, we injected Nkx2.1-Cre mice intrastriatally with an AAV-h4MDi-mCherry-DIO, to selectively express in SIs a modified inhibitory muscarinic receptor that can be pharmacologically activated by clozapine-N-oxide (CNO). Our preliminary results show that about 25% of the transfected mice show abnormal movements when after intraperitoneal administration of CNO, although less marked than those observed after SI ablation. Moreover, inhibition of SIs increased locomotion and spontaneous repetitive behaviors. Further studies are needed to confirm these findings.

Celina Goyeneche

Laboratorio de Memoria, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” (IBCN), Facultad de Medicina, UBA-CONICET

Second wave of Covid 19 pandemic in Argentinian population: vaccination results in a decrease in depressive symptoms.

Covid-19 is a disease caused by the coronavirus SARS-CoV-2. So far, up to May 2021 it has caused 4.42 million deaths on the planet and 110,000 originated in Argentina. In addition to the many physical illnesses directly associated with the Covid-19, it also causes psychological disorders such as depression and anxiety. In this work, we studied the progression of the self-perceived levels of generalized anxiety disorders (GAD) and depression in two adults groups with 18-30 and 31-50 years old. Both of them were surveyed during the first (November 2020) and the second (May 2021) waves of the SARS-CoV-2 outbreak, in the Buenos Aires Metropolitan Area, Argentina. We used the PHQ-9 and GAD-7 tests to evaluate depression symptoms and GAD levels. We also asked about weekly physical activity and the vaccination status to analyze their impact as possible protective factors of the population’s mental health after such a prolonged period of pandemic. Our data show that in both age groups, GAD increased during the second wave, while depression decreased. These tendencies are valid for both men and women. We also found a positive correlation between generalized anxiety and depression in both waves. Vaccination showed no significant effect in GAD, but a decrease in depression levels for the 31-50 group. In concordance with our previous works, physical activity seems to act as a protective factor that mitigates GAD and depression levels.

Gabriela Verónica Nieva

IFIBIO Houssay, Grupo de Neurociencia de Sistemas, Facultad de Medicina, Universidad de Buenos Aires - CONICET

Region-specific features of early microglial activation in a conditional mouse model of TDP-43 proteinopathies

Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. We have shown that transgenic mice conditionally overexpressing human nuclear wild-type TDP-43 protein (hTDP-43-WT) in forebrain neurons, recapitulate key features of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). After 1 month expression of the transgene, this mouse model displays impairment in cognitive and social behaviors in the absence of motor abnormalities. We previously described early-stage microglial activation in these mice by analyzing fold change in percentage of Iba1+ area in selected cortical and hippocampal regions. To extend these previous findings, we now performed a quantitative assessment of microglial morphology using Iba1 immunofluorescence. We found an increased number of Iba-1-labelled microglia in motor cortex (MC), in addition to longer perimeter and larger soma size in prefrontal (PFC), somatosensory (SSC) and motor cortices. Sholl analysis of microglia from MC and SSC revealed a reduction in branch complexity as we found a decrease in total process length, fewer total intersections and a significant decrement in branching 16–20 μm away from the soma, compared to control mice. In sum, these results detailing microglial morphological features expand our understanding of the relationship between early-stage neuroinflammatory processes and behavioral deficits in TDP-43 animal models of FTD/ALS.

Daniela Piña Novo

Grupo de neurociencia de sistemas, IFIBIO "Houssay"-UBA-CONICET

Altered beta bursts in the motor cortex after dopamine depletion and levodopa medication in a rodent model of Parkinson's disease

The nigrostriatal degeneration developed during Parkinson’s disease (PD) leads to changes in basal ganglia functioning that ultimately impacts the motor cortex; leading to abnormal patterns of neuronal oscillations that emerge in the primary motor cortex (M1) after dopamine depletion and during dyskinesia associated to chronic treatment with levodopa, which is the gold standard antiparkinsonian medication. Using electrophysiological single unit and local field potential recordings from mice model of PD, we identified the altered properties of M1 beta bursts (15–35 Hz) that have a significant association with motor impairment in PD. We also demonstrated that beta persistence is related to slow movement initiation in the parkinsonian condition. Furthermore, we unraveled how pathological beta activity is modulated during the time-course of levodopa administration and its relationship with gamma oscillations (60-95 Hz); resulting the gamma amplitude modulation by beta phase as the hallmark of the symptomatic “off” medication state.

Carlos Alfredo Pretell Annan

Grupo de Neurociencia de Sistemas / Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO-Houssay) / UBA-CONICET

Temporal assessment of behavioural alterations and sex influence in an NMDA receptor knockout model of schizophrenia.

Schizophrenia (SZ) is a chronic mental disorder frequently emerging between adolescence and adulthood and encompassing various symptomatic domains. It affects both males and females but clinical differences have been observed. Although the etiology of SZ is still misunderstood, alterations of GABAergic interneurons (INs) are considered to be pathophysiologically relevant since alterations in cortical INs expressing parvalbumin (PVs) have been found in patients. Normal wiring of cortical circuits relies on the proper postnatal maturation of PVs; thus, alterations of these INs could be related to the neurodevelopmental aspect of SZ. We have shown that ablation of NMDA receptors in cortical GABAergic INs from mice at early postnatal age results in SZ-like phenotypes that emerge during adulthood. However, their precise trajectory had not been fully described and sex differences were not assessed. Here, we characterized the time course of behavioral phenotypes (P25-150), evaluating sex differences and presymptomatic stages. As expected, behavioral phenotypes in male KO mice emerged once adolescence was completed, but female KO mice displayed a more complex trajectory, with transient impairments in Y-maze spontaneous alternation before adolescence and abnormal marble burying responses around the transition from adolescence to adulthood. Thus, while the majority of SZ-related phenotypes emerge in adulthood, specific traits may be present at early stages in a sex-specific manner.

Daniela Alejandra Cassano

Neurophysiology Laboratory / IMBICE / CONICET-UNLP-CIC

Growth hormone secretagogue receptor is required to enhance reward-related behaviors adaptations toward palatable stimuli in calorie-restricted mice

Ghrelin is a stomach-derived hormone that acts via growth hormone secretagogue receptor (GHSR). GHSR is expressed in the mesolimbic pathway, especially in the ventral tegmental area (VTA) that innervates the nucleus accumbens (Acb). Since plasma ghrelin levels increase under calorie restriction, GHSR signaling could act in the mesolimbic pathway and affect reward-related behavioral adaptations. We investigate the cFos neuronal activation marker induction in the mesolimbic pathway as well as the saccharine consumption in wild-type (WT) mice and GHSR-deficient mice during a 5-day 60% calorie restriction protocol. GHSR-deficient mice showed: 1) a more severe weight loss and hypoglycemia, 2) a similar increase of cFos in the VTA but a smaller increase of cFos in the Acb, and 3) a reduced overconsumption of saccharin, than WT mice during the calorie restriction protocol. When CR mice were refed, we found that GHSR-deficient and WT mice did not show different hyperphagia or glycaemia but GHSR-deficient mice show reduced saccharine consumption as compared to WT mice. Thus, we conclude that GHSR plays a main role during, and after, a calorie restriction condition. In particular, we found GHSR seems to be required for the maintenance of energy balance and glucose homeostasis as well as for the full calorie restriction-induced activation of the reward-related brain centers and saccharine overconsumption during and after calorie restriction.

Joaquin Ezequiel Gonzalez

Laboratorio de Inteligencia Artificial Aplicada / Facultad de Ciencias Exactas y Naturales / Universidad de Buenos Aires

Low frequency brain representation of acoustic features during goal oriented dialogue

During dialogue, speakers rapidly process different aspects of speech in order to respond and continue engaged. In particular, acoustic/prosodic features encode different intentions and emotions, allowing a fluent communication. The aim of this work is to better understand how the speech envelope and the voice pitch from the preceding 500 ms are encoded in the brain. Previous studies explore these features in highly constrained contexts and stimuli, such as pre-recorded sentences or radio monologues. Here, we analyse electroencephalography (EEG) data and audio recordings from pairs of participants engaged in unconstrained dialogue while performing collaborative tasks. Overall, our results follow very similar patterns to previous work but in a novel, less constrained scenario. By inspecting brain activity oscillations, we observe that the information contained in these features is encoded mainly in the low-frequency EEG bands (delta: [1 4]Hz and theta: [4 8]Hz) with a latency lower than 300 ms. Moreover, we show a better performance in predicting the EEG signal than previous studies, in particular in the frontal electrodes, with correlation values between prediction and signal of up to 0.3, suggesting that these features become even more relevant during natural speech. The present work paves the way for studying brain representations of more complex aspects of speech in natural context, such as phonological features or speech acts characteristics.

Alejandro Nasimbera

ENYS CONICET - UNAJ - HOSPITAL EL CRUCE

Diagnostic Performance of MRI Volumetry in Epilepsy Patients With Hippocampal Sclerosis Supported Through a Random Forest Automatic Classification Algorithm

Introduction:Many methods offer volumetry services for MR data used to assist in clinical diagnosis of hippocampal sclerosis (HS).Association between severity of histopathological anomalies and hippocampal volumes was reported using MR volumetry with a higher diagnostic yield than visual examination. Interpretation of volumetry is challenging due to methodological differences and variability of hippocampal volume.We aimed to quantify diagnostic yield from two techniques: FreeSurfer v.06 and volBrain-HIPS. Methods:Volumetry measures were calculated using MRI from 61 healthy controls and 57 patients with unilateral HS.We validated the results by a machine learning classification algorithm (Random Forest) computing accuracy and feature relevance to distinguish between patients and controls.Mean reference values and 95% confidence intervals were calculated for left and right hippocampi along with hippocampal asymmetry to test diagnostic accuracy. Results:Bothmethods showed excellent classification performance (AUC:> 0.914) with differences in absolute (cm3) and normalized volumes. Hippocampal asymmetry was the most accurate discriminator from all estimates (AUC:1~0.97). Similar results were achieved in the validation test with an automatic classifier (AUC:>0.960). Conclusion:We calculated reference volumetry values from two methods to accurately identify patients with HS. Validation with an automatic classifier confirmed the principal role of the hippocampus for diagnosis.

Gustavo Ezequiel Perez

Medical Physics Department, Centro Atómico Bariloche, CNEA-CONICET, San Carlos de Bariloche, Argentina

Assesing the usefulness of an optogenetics setup to study the circadian clock of Drosophila melanogaster

Light-triggered neural activation, or optogenetics allows the manipulation of neural activity with millisecond precision. The simplest protocol is to express, light-gated ion channel in neurons of interest. We built an optogenetic setup to study neural circuits that control the circadian clocks in flies. As Drosophila, is supposed to be blind to red-shifted wavelengths, in this work we employed Chrimson, a red-shift ChR2 variant, to in vivo activate neurons without disturbing the circadian rhythms. By expressing Chrimson in fruitless neurons we were able to activate courtship movements in males, proving the functionality of this system in our hands. Next, we quantified neuronal activation at different wavelengths, intensities and stimulation times, employing the courtship behavior as a readout. We found that high light intensities were needed to evoke behavioral changes. Then, as DN1p neurons control sleep and circadian rhythms, we drove the expression of Chrimson onto these neurons. Surprisingly, we observed a clear increase in locomotor activity of control flies during light pulses, suggesting that these flies can see red light. This increase of activity is much less pronounced in flies expressing Chrimson, which suggests that the opening of the channels partially suppresses the activity increase. Thus, even though our results may support earlier findings, they also cast some doubts on the usefulness of Chrimson as an optogenetic tool to study the neural control of sleep.

Fermín Travi

Instituto de Investigación en Ciencias de la Computación (ICC) Pabellón I, Ciudad Universitaria, CABA

Benchmarking human visual search computational models in natural scenes: models comparison and reference datasets

Nowadays, several algorithms are able to predict gaze positions during simple observation, but few models attempt to simulate human behavior during visual search in natural scenes. Moreover, these models vary widely in their design and exhibit differences in the configuration of their datasets and metrics employed. Thus, there is a need for a reference point, on which each model can be tested, and from where potential improvements to the algorithms can be derived.
Three models were considered: a Bayesian model (cIBS), one based on a CNN (IVSN), and one based on reinforcement learning (IRL). Each of them had its own dataset and was evaluated on all of them. The analysis was centered on performance and similarity to humans.
Not surprisingly, each model performed best on its own dataset. However, cIBS displayed the greatest similarity to humans in all of them. IRL performs categorical visual search and, thus, generalized poorly to other datasets. IVSN was great at ﬁnding objects, but failed to capture human behavior. Interestingly, human observers didn’t display common distractions, such as looking at human faces, but cIBS did. Furthermore, humans are strongly guided by context, whereas the models ignore where objects are commonly located in a scene.
Incorporating the context of a scene seems to be crucial for capturing human behavior. The present work shows the urgency for common metrics and datasets for the development of more general visual search models in natural scenes.

OC-3

CHAIRS:
María Ana Contin
Gastón Bisig
Mauricio Galiano

ZOOM LINK

Ivana Leda Bussi

1. Laboratorio de Genética del Comportamiento / Fundación Instituto Leloir - IIB-BA CONICET - 2. de la Iglesia Lab/ Department of Biology/ University of Washington

Deletion of the vesicular GABA transporter from NeuromedinS+ SCN neurons impairs behavioral circadian rhythms in mice.

In mammals, the suprachiasmatic nuclei of the hypothalamus (SCN) houses the master circadian clock. The SCN in rodents consists of approximately 20,000 neurons, and among the multiple peptides and neurotransmitters expressed in the SCN, GABA is the most prevalent. While GABA has been shown to be involved in the coupling between SCN cellular oscillators it is not clear whether GABAergic transmission within the nucleus is essential to sustain circadian rhythms. In the present study, we used targeted mutagenesis to knock out the vesicular GABA transporter (Vgat) from NeuromedinS (NMS+) neurons in the SCN of mice. While all mice carrying the homozygous deletion of Vgat in the NMS+ cells of the SCN (Nms-Vgat-/-) were able to synchronize their wheel-running activity to a normal light-dark cycle, 60% of them failed to show circadian activity patterns after being switched to constant darkness. Nms-Vgat-/- mice showed the expected decreased VGAT expression in the SCN as well as decreased expression and altered distribution of the neuropeptide VIP, which is critical for normal SCN function. Furthermore, when the persistency of the rhythmic expression of clock genes in ex-vivo SCN explants was evaluated through Per2-luciferase expression, Nms-Vgat-/- mice showed faster damping of the oscillations. Taken together our data suggest that GABA signaling may have a critical role in the orchestration of behavioral circadian rhythms and the development of SCN neuronal network properties.

Laura Alethia de la Fuente

COCUCO/DF-IFIBA/UBA

Temporal reversibility of neural dynamics as a signature of consciousness

The brain is capable of constructing representations of the world including the direction of time. In this work, we investigated whether this can be decoded from electrocorticography (ECoG) recordings in non-human primates in different states of consciousness (awake, sleep and ketamine). Time courses of the principal components (PC) of the data were transformed to frequency and phase spectrograms and used as the input of a convolutional network trained to distinguish original vs. time reversed epochs. In total, 16,200 models were fitted for 81 conditions (3 levels of model complexity, 3 types of data, 3 PCs, in 3 states of consciousness) with 100 iterations each. This was repeated after randomizing data labels to construct a null model. Unshuffled models yielded a significantly higher performance (p <0.001). For wakefulness, the AUC in the validation set was always above .75. In the case of sleep, the best performance was observed for the models that included the phase information. For the ketamine condition, significant performance was observed for the most complex models. In the frequency domain, a greater relative importance was observed for high frequencies. Particularly in sleep, the importance was highest for the phase data. In summary, deep convolutional network models were able to predict the direction of time from ECoG data during wakefulness, but this prediction was hindered in states of reduced awareness such as deep sleep or under ketamine anesthesia.

Juan Ignacio Ispizua

Laboratorio de Genética del Comportamiento, IIBBA-FIL

The impact of glial signals on neuronal structural plasticity

Recently, we described that a functional glial clock is necessary for circadian plasticity in the small lateral ventral neurons (sLNvs), a group of key pacemaker neurons of D. melanogaster. Circadian structural plasticity involves rhythmic changes in the degree of arborization and fasciculation of their dorsal termini. The sLNvs express PDF, a neuropeptide relevant in the synchronization of the clock network that oscillates in phase with this remodelling process. We have previously demonstrated that circadian plasticity modifies the way the pacemaker circuitry is wired regularly, but its impact on behaviour and the molecular basis that control this process are yet to be defined. Building upon our previous results, we examine in depth the impact of neuronal-glial connectivity. Using GFP reconstitution analysis (GRASP), we found that sLNv termini contact directly with two different glial subtypes (astrocyte-like and ensheathing glia) and that these contacts are time-of-the-day dependent. Interestingly, blocking adult glio-transmission has different effects on PDF levels and plasticity depending on the type of glia recruited and the length of the treatment (12 or 24 hours). Additionally, preliminary experiments show that preventing clock oscillations in different glial subtypes affect circadian plasticity distinctively. Taken together, our results suggest a complex glial implication in the modulation of adult structural plasticity with distinct roles for different glial subty

Giovanna Margarita Velázquez Campos

Genética del comportamiento, Fundación Instituto Leloir

The role of orsai in circadian rhythms

Rhythmic rest-activity cycles are controlled by an endogenous clock. In Drosophila, the circadian network resides in about 150 neurons organized in groups, out of which the group of ventral lateral neurons (LNv) is essential in the control of rest-activity cycles. Previous results from our laboratory suggest that chronic orsai dysregulation (osi, an important gene in lipid catabolism) within the LNvs affects circadian patterns of locomotor activity in young and aged flies. To understand osi ´s role in the adult brain, genetic tools were used to downregulate osi levels in an adult-specific way, and thus evaluate the impact of osi on the clock neurons. We show that adult-specific osi knockdown in LNv neurons lengthens the period and reduce the consolidation of circadian locomotor activity patterns in young flies. Concomitant expression of its human ortholog ETFRF1 rescues the period phenotype observed. Moreover, ETFRF1 expression in the context of OSI knockdown in aged animals results in flies with properties reminiscent of younger individuals. In addition, decreasing osi levels in this key group of circadian neurons affects the morning anticipation both in young and aged groups under daily conditions, likely through the modulation of PDF levels. Together these results suggest that osi plays a fundamental role in LNv physiology.

María Ayelén Caramés

Laboratorio de la conciencia, IFIByNE, CONICET-UBA

FREQUENCY AND EMOTIONAL PRIMING COULD MODULATE COMPLEX DECISION-MAKING PROCESSES DEPENDING ON TASK RELEVANCE

Complex decision-making processes (CDM) differ from simple ones because they require greater cognitive commitment and higher response time (RT). We evaluated in previous cognitive experiments if repetition (RP) and emotional priming (EP) modulate CDM by presenting faces (4) sequentially, with different frequencies (1, 6 or 12 repetitions) in RP experiments or associated with one emotional content phrase (positive, negative or neutral) in EP ones. Subjects were randomly divided into 2 groups by asking them to choose a face to realize an important task (IT) or without specifying the task (NST). Results indicated that CDM processes could be modulated by both priming when the task was not specified (NST group), but not when the choice was made to do an important task (IT group), when RT was higher. These experiments raise the role of the task´s nature in a possible top-down mechanism modulating CDM. Here we analyse a third group, asked to choose a face to realize a not important task (NIT), replicating the same online experiments and compared to a new NST group. Results show that: 1. When RP was assessed, the face with frequency 12 was significantly more chosen in NST than in NIT and RT in NIT is significantly longer than NST; 2. When EP was evaluated, NIT group has chosen more significantly faces associated with negative or neutral phrases (than positive and than NST group). These results support the hypothesis that priming modulation could be affected by the task´s relevance.

Juliana Fatima Dalto

Laboratorio de la conciencia, IFIByNE, CONICET-UBA

Consolidated Aversive Memories are hard to forget

Although it has been demonstrated the existence of active forgetting (AF) for several acquired experiences, there is poor evidence about this process for consolidated aversive memories (CAMs). Previously, we have shown that blockade of D1 receptors in the ventral tegmental area (VTA) or positive allosteric modulation of GABAA receptors in the hippocampus (HP) or via systemic administration do not cause AF of CAMs in rats. Here we first decided to extend our analysis on the role of GABAergic system administering a low dose of a specific agonist. Neither the infusion of muscimol in the HP nor in the VTA after inhibitory avoidance (IA) training modified the duration of this memory. Then, based on previous and controversial studies, we next decided to assess the role of the GTPase Rac1 in AF. Our results show that post-retrieval inhibition of this protein by NSC23766 infusion in the HP or the VTA of male and female rats did not affect the maintenance of IA memory. So far, our results do not support the participation of D1 receptors nor GABAA receptors nor Rac1 in an AF mechanism for CAMs in the HP or the VTA. One explanation could be that we are failing to find the correct pathway/region where AF is occurring. Other possibility indicates that AF might not dictate the fate of CAMs. Since these memories are strongly relevant for individual’s survival, the lack of AF controlling its persistence could have adaptive implications.

Graciela Ines Kearney

Redes neuronales, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE)

Coordination of neural activity across segments

In animal motor behaviors, the segments along the antero-posterior axis perform movements in a coordinated manner. Leeches are an outstanding model to analyze the underlying neuronal network controlling this function because the 21 segments that compose the body are virtually identical, simplifying the question on intersegmental coordination to that on interactions among iterated units. Leeches crawl over solid surfaces through a succession of elongation and contraction body waves, anchored on the posterior and anterior suckers. Each segment bears all the neurons required to produce this rhythmic motor pattern and dopamine evokes fictive crawling in isolated midbody ganglia. The rhythmic motor pattern can be also elicited in chains of three ganglia in a coordinated way. The activity pattern in both experimental conditions is highly similar, and fits behavioral parameters. To analyze the degree of interaction of the local segments along the chain we manipulated the membrane potential of the premotor nonspiking neurons. A hyperpolarization of this neuron that in isolated ganglia annuls the crawling motor pattern, produces a minor slowdown in the chain. The results indicate that isolated short ganglion chains have all the elements necessary to produce coordinated activity, but the network cannot be considered as a series of interacting autonomous segmental units. Within the chain, the segmental networks are integrated in a global network that subdues the segmental units.

Nicolás Martorell

Laboratorio de Redes Neuronales / Instituto de Fisiología, Biología Molecular y Celular / UBA-CONICET

Audiovisual integration in the Mauthner cell enhances escape probability and reduces response latency

Fast and accurate threat detection is critically important for animal survival. Reducing perceptual ambiguity by integrating multiple sources of sensory information can enhance threat detection and reduce response latency. However, studies showing a direct link between behavioral correlates of multisensory integration and its underlying neural basis are rare. In fish, an explosive escape behavior known as C-start is driven by an identified neural circuit centered on the Mauthner cell. The Mauthner cell can trigger C-starts in response to visual and auditory stimuli allowing to investigate how multisensory integration in a single neuron affects behavioral outcome after threat detection. Here we demonstrate that in goldfish visual looms and brief auditory stimuli can be integrated to increase C-start probability and that this enhancement is inversely correlated to the saliency of the cues with weaker auditory cues producing a proportionally stronger multisensory effect. We also show that multisensory stimuli reduce response latency locked to the presentation of the auditory cue. Finally, we make a direct link between behavioral data and its underlying neural mechanism by reproducing empirical data with an integrate-and-fire computational model of the Mauthner cell.

Matias Mugnaini

Fundacion Instituto Leloir (IIBBA)

Remapping of CA3 ensembles induced by optogenetic stimulation of young but not mature adult-born granule cells in free-foraging mice

Hippocampal adult-born granule cells (aGCs) are transiently hyperplastic and excitable around developmental week 4, and reach a mature physiology around week 10. While the activity of aGCs during this transition has been characterized, its influence on their main target CA3 is still poorly understood. In this work, we studied the impact of optically stimulating young (4 weeks) or mature (8 weeks) cohorts of aGCs expressing channelrhodopsin-2 on the electrophysiology of downstream CA3 neurons in free foraging mice. The early evoked response (onset: 5-13 ms) of individual CA3 cells was similar for both cohorts, although mature aGCs recruited more postsynaptic neurons (3 vs 14 %). In addition, a subset of CA3 cells presented a conspicuous late-onset response that was evoked exclusively by mature aGC stimulation. We also investigated if repeated optogenetic stimulation might alter stable CA3 spatial maps built in a familiar arena. We found significant remapping in the proximal half of CA3 when stimulating young but not mature aGCs. The same manipulation 2 days later did not induce remapping, suggesting a strong one-shot plasticity phenomenon. Our results are in line with the proposed role of adult hippocampal neurogenesis in spatial discrimination. The continuous addition of cells capable of triggering one-shot remapping could be a key mechanism for the encoding of new episodic memories without mutual interference in downstream CA3 networks.

Martina Radice

Neuronal Networks Lab - IFIBYNE - CONICET/UBA

Neuronal Networks: Balancing Motor Outputs

The execution of rhythmic motor behaviors requires multiple control mechanisms to adjust the behavioral output, narrowing down the degrees of freedom of a system with multiple active units. Leeches crawl on solid surfaces through a succession of elongation and contraction body waves, anchored on the posterior and anterior suckers. Each segmental ganglion contains all the neurons required to produce this rhythmic motor pattern, and dopamine evokes fictive crawling in isolated midbody ganglia. The pair of premotor NS (nonspiking) neurons are connected to motoneurons through a central network that provides recurrent inhibitory signals onto the motoneurons. We aim at understanding the role of NS in the context of crawling. During fictive crawling NS neurons receive inhibitory signals, tuned to the contraction phase of crawling, monitored through the DE-3 motoneuron. The results suggest that the inhibitory signals in NS are delivered by the rhythmogenic circuit that controls the motoneuron output. Thus, excitatory signals to DE-3 are correlated to inhibitory signals in NS that, in turn, can restrict the motoneuron activity. To this point the data indicates that the premotor NS neuron acts as an homeostatic element, restricting the motor output. Our future work will determine if this is a global effect onto the motoneuron population or whether it is directed to specific motoneurons, sculpturing the motor pattern.

OC-4

CHAIRS:
Patricia Setton
José Biurrun

ZOOM LINK

Natalia Giannina Armando

1. Biomedicine Research Institute of Buenos Aires - CONICET - Partner Institute of the Max Planck Society, Buenos Aires, Argentina. 2. Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA-MPSP-CONICET) 2 Universidad Nacional de Quilmes, Departamento de Ciencia y Tecnología. Buenos Aires, Argentina.

Signaling pathways mediated by CRHR2α in neuronal cell contexts

The corticotropin-releasing hormone (CRH) system, its ligands (CRH and urocortins 1-3) and receptors (CRHR1 and CRHR2) drive the response and adaptation to stress. Dysregulation of the CRH system is causally linked to stress-related psychiatric disorders. The CRHR2α splice variant, the main isoform in the mouse brain, has an uncleavable signal peptide giving this receptor special trafficking and signaling features. Our aim is to characterize UCNs/CRHR2α signaling pathways in a neuronal context using the hippocampal cell line HT22 stably expressing the receptor (HT22-CRHR2α) and primary neuronal cultures. ERK1/2, CREB and Akt were activated downstream CRHR2α in HT22-CRHR2α cells. ERK1/2 and CREB activation depended on cAMP generated by the soluble adenylyl cyclase (sAC) and transmembrane adenylyl cyclases but only sAC was required for Akt activation. Upon stimulation, HT22-CRHR2α cells undergo morphological changes that required sAC-produced cAMP and PKA activation independently of ERK1/2 activation. We observed an unusual trafficking for the CRHR2α due to the pseudo-signal peptide: the fraction of the receptor in the cell surface increased 6 min after stimulation returning to basal levels after 30 min. In primary neurons, preliminary results suggest that Fos induction by the CRH system may depend on neuronal activation and the ligand used. Our results highlight the relevance of cellular contexts and provide information to define the role of UCNs and CRHR2α in the CRH system.

Juán Facundo Chrestia

Laboratorio de Neurofisiología y Farmacología Molecular/Instituto de Investigaciones Bioquímicas de Bahía Blanca/CONICET-Universidad Nacional del Sur

A Functional Interaction Between a Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The binding of the viral spike protein (S) to angiotensin-converting enzyme 2 in host cells is crucial for infection. The S protein has been suggested to interact with nicotinic acetylcholine receptors (nAChRs), and their contribution to the COVID-19 inflammatory pathophysiology has been proposed. α7 is an interesting candidate target because it is present in neuronal and non-neuronal cells, and it has neuroprotective and anti-inflammatory actions. By whole-cell and single-channel recordings we revealed that the Y674-R685 region of the S protein shows a direct functional interaction with human α7 nAChR. The S fragment exerts a dual effect, acting as a low-efficacy agonist and a non-competitive antagonist. In agreement with molecular dynamics simulations showing stable binding of this region to the ACh binding pocket, the S fragment activates α7, but only in the presence of a potentiator, supporting its action as a very low-efficacy agonist. In addition, it allosterically inhibits α7 responses elicited by ACh, which may result in the predominant effect. This study provides unequivocal evidence supporting a functional α7-S protein interaction, which may play a role in infectivity and/or disease progression and may be explored for new therapeutic opportunities.

Clara Inés McCarthy

Instituto Multidisciplinario de Biología Celular (IMBICE-CONICET-UNLP-CIC)

Effects of the antipsychotic drug chlorpromazine on D1/D5R constitutive activity and postsynaptic currents in prefrontal cortex (PFC) neurons

The PFC is a key associative cortical region that is severely affected in patients with schizophrenia (SCZ). Changes in dopamine receptor type 1 (D1R) function and availability in the PFC are associated with working memory deficits of SCZ. We previously showed that D1R constitutive activity increases voltage-gated calcium channels CaV2.2 density in the cell surface in transfected cells and that this effect is relevant in the PFC. Here, we continue to study D1/D5R constitutive activity modulation of native CaV currents and explore its impact on synaptic activity in PFC pyramidal neurons. We performed patch-clamp experiments and cAMP measurements on transfected HEK293T cells and wild-type C57BL/6 mouse brain slices, combining two pharmacological interventions to discriminate D1/D5R activity-dependent effects: systemic administration of chlorpromazine (CPZ, D1/D5R inverse agonist) and intra-PFC infusions of SCH23390 (D1/D5R antagonist). We assessed CaV subtype contributions to total native calcium current in naïve and treated mice. Then, we evaluated the impact of this pharmacological manipulation on synaptic activity: we recorded evoked, spontaneous and miniature excitatory/inhibitory postsynaptic currents (E/IPSC). We found that CPZ-treatment decreased EPSCs while increasing IPSCs, creating an E/I imbalance that favored inhibition. We are conducting experiments to further understand the link between D1/D5R constitutive activity and the changes seen in postsynaptic currents.

Antonella Soledad Rios

Molecular and Cellular Neuroscience Division-INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES (IIBBA) ; (CONICET - FUNDACION INSTITUTO LELOIR).

Etv4 regulates peripheral innervation and the development of peptidergic sensory neurons mediating pain stimuli.

The perception of environmental stimuli in mammals is determined during embryonic development by specification of sensory neurons and peripheral innervation of the targets. Nerve growth factor (NGF) and its receptor TrkA are involved in many of these events and mediate pain sensation. The identification of molecules underlying NFG/TrkA signaling pathway is essential to understand the transduction of painful stimuli. Two members of the Pea3 subfamily of ETS transcription factors, Etv4 and Etv5, are known to be expressed by TrkA dorsal root ganglion (DRG) nociceptors and to be induced by NGF. Here we identify an essential role of Etv4 in target innervation and in the expression of the noxious-heat receptor TRPV1 in DRG neurons. Furthermore, we show that Etv4 deletion result in a reduced outgrowth of sensory neurons in response to NGF and in defects in growth cone architecture. Moreover, using different behavioral assays, we show that Pea3 deficient animals present defects in sensing thermal noxious stimuli. Together, our data reveal the relevance of Etv4 in regulating transcriptional programs involves in the transduction of pain signals.

Maximiliano Rios

CIQUIBIC-FCQ-UNC

Arylalkylamine N-acetyltransferase: “Nuclear importation and protective role against the blue light”

Arylalkylamine N-acetyltransferase (AANAT) is the key regulatory enzyme in melatonin synthesis present in the pineal gland, retina and other regions, controlled by light and the molecular clock. cAMP promotes its phosphorylation (pAANAT) triggering its activity. The vertebrate retina is a photosensitive tissue in which prolonged exposure to blue light (BL) may cause retinal damage and circadian clock disruption. Here we investigated the regulation of AANAT in primary cultures of chicken embryonic retinal cells exposed to different light conditions. AANAT expression is induced after 1h BL (1h post BL) as compared with dark (D) controls and displayed marked intracellular changes from the cytoplasm to nucleus increasing in BL and remaining elevated 1h post BL. Also, high pAANAT levels were detected in nuclear fractions of cultures after the BL treatment in comparison with D control. Knocking-down AANAT mRNA by specific shRNAs, cell viability assessed by MTT 24 h later was significantly affected by a 1h BL exposure as compared with the scramble, non-effects were observed in the dark conditions by MTT assay. In addition, ~50-60% of cells showed a significant decrease in levels of AANAT mRNA and -like protein. Results strongly suggest that AANAT is a BL-induced enzyme in retinal neuron cells, promoting its phosphorylation and nuclear localization, likely playing an important protective function in response to BL exposure.

Lucia Santadino

Laboratorio de Neuroepigenética, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires

Cocaine-base paste administration during adolescence alters the expression of genes involved in the excitatory/inhibitory balance in reward-system regions.

Cocaine base paste (CBP) is a drug of abuse consumed mostly by adolescents and young adults in a socio-economically vulnerable situation in Latin American countries. We have previously studied the effects of CBP on behavior using an open field test (OFT), resulting in an enhancement of anxiety-like behavior caused by CBP treatment. Considering that anxiety disorders are related to alterations of the excitatory/inhibitory balance, expression of genes involved in glutamatergic and GABAergic transmission was analyzed by real-time PCR in several reward-system regions. To do so, five-week-old CF-1 female mice were intraperitoneally injected daily with vehicle or CBP (40 mg/kg) for 10 day and subjected to a 10-day period of withdrawal. After that, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and amygdala (Amg) were isolated due to their implication in reward-seeking behavior. As a result, we observed a significant upregulation of Gria1, Gria2, Grin2b and Gad67 expression in the Amg of CBP-injected mice compared with the vehicle-injected group. Moreover, Gria1, Gria2, Gria3, Grin2b and Vglut presented a strong trend to increase whereas Vgat showed an opposite trend in the NAc of CBP group. Finally, the expression of Gria1 tended to increase in the mPFC of CBP mice. These results suggest that CBP administration during adolescence could lead to a disruption of the excitatory/inhibitory balance in the developing regions of the reward-system through gene expression changes

Juan Francisco Döppler

Laboratorio de Sistemas Dinámicos, Departamento de Física, FCEN, UBA; IFIBA-CONICET

Synthesizing avian dreams

Replays of behaviour-related neural activity during sleep have been shown to occur in different species, including rodents and oscine birds. In oscine birds, it has been shown that, while the pressure gesture needed to produce song is inhibited during sleep, these events of neural activity do arrive at the muscles of the syrinx (the avian vocal organ). These events of song-like muscle activity during sleep have also been observed in suboscine birds, which are usually considered non-learners. While in suboscines there is little knowledge about the neural structures related to song production, we here argue that biomechanics provides a unique window to study sleep replays. Firstly, because the signals arriving at the muscles represent the integrated output of the central nervous system. On the other hand, we have a more complete understanding of the physical mechanisms by which these instructions are translated by the muscles into specific properties (such as tension of the oscillating tissue), and therefore into sound. In this work we show how dynamical models of the biomechanics can be used to translate this activity into behaviour, to create biophysically plausible renditions of sound even when the patterns of activity are quantitatively different from those used during song production. In other words, we show how biophysical models can be applied to translate the EMG signals at the syringeal muscles into sound, to listen to what a bird is dream-singing.

Constanza Miguel

Instituto de Biología y Medicina Traslacional

Chemotherapy-induced changes in the expression of transient potential receptors in dorsal root ganglia and spinal cord of both male and female animals: implications for neuropathic pain generation.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a frequent and debilitating side effect of cancer therapy. Transient potential receptors (TRPs) are non-selective cation channels involved in the detection of thermal, chemical and mechanical stimuli and in the neurotransmission of pain. Their role in CIPNP has recently begun to be explored, as well as the existence of sex differences in pain behaviors in animals receiving chemotherapy. Here we evaluated the development of mechanical and cold allodynia in animals exposed to oxaliplatin, analyzing the existence of sex-related differences, as well as changes in the expression of TRPV1, TRPM8 and TRPA1 in the dorsal root ganglia (DRGs) and spinal cord (SC). Animals were injected with oxaliplatin, allodynia was evaluated using von Frey and Choi tests, and the mRNA levels of TRPs were evaluated by real time RT-PCR. Oxaliplatin administration induced the development of mechanical and cold hypersensitivity and allodynia in both male and female animals (p<0.05 vs control in both cases). No significant sex-related differences were observed. Oxaliplatin induced a significant increase in the expression of TRPV1 and TRPM8 in DRGs and SC from both male and female animals, while TRPA1 mRNA levels were increased only in ganglia (p<0.05 vs control in all cases). Our results show that the upregulation of TRPV1, TRPM8 and TRPA1 might be involved in oxaliplatin-induced mechanical and cold allodynia in males and females.

Jorge Mirande

Neurobiology of Movement Lab, Medical Physics Dept, Instituto Balseiro, UNCUYO-CNEA

Decoding of neural signals during the execution of motor skills in the mesencephalic locomotor region.

The Mesencephalic locomotor region (MLR) is a shared structure among many species of the animal kingdom, from lampreys to human beings, classically known to contribute both to the generation and control of locomotion. Recent findings have highlighted the great functional and anatomical heterogeneity residing within MLR. While glutamatergic neurons in the dorsal MLR (cuneiform nucleus) are related to high-speed escape-like locomotion, in the ventral portion of MLR coexist different glutamatergic neuronal subpopulations involved in a range of behaviors beyond locomotion, such as rearing, grooming or handling. But, can this classification be taken even further? Can MLR neurons encode particular postures or movements? We have previously used unsupervised machine learning techniques to classify different types of recurrent movements executed by mice performing a motor skill learning task known as accelerating rotarod. In this work, we took advantage of the obtained movement classification to align the neuronal activity recorded extracellularly in MLR. By doing so, we were able to identified MLR neurons that are significantly modulated by specific postures or pose sequences. We then assessed whether neurons were recruited by other events such as a sudden fall of the tail base. Altogether, our data showed that MLR neurons are able to encode particular aspects of the executed movement.