Biology subjects

Jabarin, R.

Publications and source records attributed to Jabarin, R..

5 recordsLinked to original sources

bioRxiv2025

Inhibition governs stimulus preference encoding in mPFC pyramidal neurons during a social choice

Social decision-making requires the brain to evaluate competing options and select appropriate actions. The medial prefrontal cortex (mPFC) is implicated in social cognition and value-based decision-making, yet how it encodes the relative value of competing social choices remains unclear. Here, we used fiber photometry, optogenetics, and projection-specific recordings in mice performing four binary social discrimination tasks to examine how mPFC pyramidal neurons encode social choice. We found that these neurons showed marked inhibition during bouts toward the preferred stimulus. This inhibition was specific to transitional bouts, when animals switched between stimuli, and was absent during repeated, non-transitional bouts. Negative calcium transients predicted subsequent investigation of the preferred stimulus, indicating a functional role in guiding choice. Importantly, this inhibition encoded relative stimulus value rather than identity. Optogenetic activation of mPFC pyramidal neurons during investigation induced immediate avoidance, yet paradoxically promoted persistent re-engagement with the same option through repetitive non-transitional bouts. Projection-specific recordings further revealed differential recruitment of mPFC neurons targeting the nucleus accumbens and basolateral amygdala across tasks. Together, these findings identify inhibition of mPFC pyramidal neurons as a neural signature of stimulus preference, revealing a principle by which the mPFC dynamically guides social choice.

neuroscience↗

bioRxiv2024

Distinct prelimbic cortex neuronal responses to emotional states of others drive emotion recognition in adult male mice

The ability to perceive the emotional states of others, termed emotion recognition, allows individuals to adapt their conduct to the social environment. The brain mechanisms underlying this capacity, known to be impaired in individuals with autism spectrum disorder (ASD), remain, however, elusive. Using the emotional state preference paradigm, we show that adult mice can discern emotional states of conspecifics in a sex-specific manner, behavior impaired in an ASD mouse model. Fiber photometry revealed inhibition of pyramidal neurons in the prelimbic medial prefrontal cortex (PrL) during investigation of aroused individuals, as opposed to transient excitation towards non-aroused conspecifics. Augmenting this differential neuronal response enhanced emotion recognition, while abolishing this response eliminated such behavior, as demonstrated via optogenetic stimulation. Chronic electrophysiological recordings at the single-cell level indicated social stimulus-specific responses in PrL neurons at the onset and conclusion of social investigation bouts, potentially regulating the initiation and termination of social interactions. The dysregulated activity of these neurons may thus contribute to deficits in social behavior observed in ASD.

neuroscience↗

bioRxiv2023

Impaired emotion recognition in Cntnap2-deficient mice is associated with hyper-synchronous prefrontal cortex neuronal activity

Individuals diagnosed with autism spectrum disorder (ASD) show difficulty in recognizing emotions in others, a process termed emotion recognition. While human fMRI studies linked multiple brain areas to emotion recognition, the specific mechanisms underlying impaired emotion recognition in ASD are not clear, partially due to the lack of appropriate tests in animal models. Here, we employed an emotional state preference (ESP) task to show that Cntnap2-knockout (KO) mice, an established ASD model, do not distinguish between conspecifics according to their emotional state. We assessed brain-wide local-field potential (LFP) signals during various social behavior tasks and found that Cntnap2-KO mice exhibited higher LFP theta and gamma rhythmicity than did C57BL/6J mice, even at rest. Specifically, Cntnap2-KO mice showed increased theta coherence, especially between the prelimbic cortex (PrL) and the hypothalamic paraventricular nucleus, during social behavior. Moreover, we observed significantly increased Granger causality of theta rhythmicity between these two brain areas, across all types of social behavior. Finally, optogenetic stimulation of PrL pyramidal neurons in C57BL/6J mice impaired their social discrimination abilities, including ESP behavior. Together, these results suggest that increased activity of PrL pyramidal neurons and their augmented synchronization with specific brain regions are involved in the impaired emotion recognition exhibited by Cntnap2-KO mice.

neuroscience↗

bioRxiv2022

Neural activity and theta rhythmicity in the anterior hypothalamic nucleus are involved in regulating social investigation

Social interactions are highly complex, involving both approach and avoidance actions towards specific individuals, dependent on the social context. Currently, the brain regions subserving these behaviors are not fully known. The anterior hypothalamic nucleus (AHN) is a relatively unstudied and poorly defined brain area, known as part of the medial hypothalamic defensive system. Recent studies that examined the role of the AHN in various contexts have yielded contradicting results regarding its contribution to approach, avoidance, and escape behaviors. Yet, none of these studies has directly examined its role in social interactions. Here we explored the role of AHN neurons in regulating approach and avoidance actions towards distinct stimuli during various types of social interactions, using electrophysiological recording of neural activity in the AHN of behaving mice, c-Fos staining, and direct optogenetic stimulation. We found that theta rhythmicity in the AHN was enhanced during affiliative interactions, but decreased during aversive ones. Moreover, spiking activity of AHN neurons was found to be elevated more persistently during investigation of social stimuli, as compared to objects. Notably, AHN neuronal firing was found to be modulated by theta rhythmicity during social interactions. Finally, we found that during social interaction, direct optogenetic stimulation of AHN neurons augmented approach behavior towards stimuli associated with the optogenetic activation. Overall, our results suggest a context-dependent role for AHN neuronal activity in regulating approach behavior during social interactions, and for theta rhythmicity in mediating the valence of the social context.

neuroscience↗

bioRxiv2020

Precision medicine for the rescue of specific impairments in social behavior associated with the A350V Iqsec2 mutation

In this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. We found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.

neuroscience↗