Biology subjects

Netser, S.

Publications and source records attributed to Netser, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Sex differences in neural activity across amygdalo-striatal network during social behaviour

BackgroundSocial behaviour is essential for the survival of most mammalian species and is shaped by sex-dependent genetic and endocrine factors. However, how sex influences brain-wide neural dynamics during social interactions remains poorly understood. MethodsHere, we investigated sex differences in neural activity across a distributed amygdalo-striatal network in freely behaving mice. Using chronically implanted electrode arrays, we simultaneously recorded extracellular activity from multiple amygdalo-striatal regions while mice performed four social discrimination tasks. Neural signals were analysed alongside video-based behavioural tracking and head acceleration measurements. ResultsWe identified significant sex differences in neural activity that emerged even before social interaction, suggesting distinct anticipatory network states. During social interaction, sex differences were distributed across brain regions and electrophysiological features, but were most consistently expressed in the basolateral amygdala (BLA). Notably, BLA activity exhibited pronounced sex-specific, context- and time-dependent dynamics, particularly during the initial phase of social interaction. These neural differences were associated with variations in behavioural responses and movement dynamics. ConclusionsTogether, our findings reveal that sex shapes both baseline and interaction-driven neural activity across the social brain network, and highlight the BLA as a key node underlying sex-specific dynamics of social behaviour. Plain English summarySocial behaviour is essential for survival and differs between males and females in many species, including humans and mice. These differences are influenced by biological factors such as genes and hormones, but how they are reflected in brain activity during social interactions is still not fully understood. In this study, we examined how brain activity differs between male and female mice during social behaviour. We recorded neural activity simultaneously from several brain regions involved in social and emotional processing while mice performed four different social interaction tasks. These tasks tested preferences for social versus non-social stimuli, opposite-sex animals, isolated animals, and stressed animals. At the same time, we monitored behaviour and head movements using video tracking and motion sensors. We found that males and females showed distinct patterns of brain activity even before social interaction began, suggesting that the brain may enter different "anticipatory" states depending on sex. During social interaction, sex differences in neural activity varied depending on the social context and the stage of the interaction. The strongest and most consistent differences were observed in the basolateral amygdala, a brain region known to regulate emotional and social behaviour. Interestingly, these neural differences were linked to differences in movement dynamics and social responses, particularly during the first moments of interaction. Our findings suggest that sex shapes both baseline brain activity and the way the brain responds during social encounters. This work improves our understanding of the neural basis of sex differences in social behaviour and may help inform future research on psychiatric conditions that affect social functioning differently in males and females. HighllightsO_LISimultaneous multi-site recordings revealed sex-dependent neural dynamics across an amygdalo-striatal social brain network during social behaviour. C_LIO_LIMale and female mice exhibited distinct electrophysiological signatures even before social interaction, suggesting sex-specific anticipatory neural states. C_LIO_LIHigh-frequency local field potential oscillations showed the strongest and most consistent sex differences across behavioural contexts and brain regions. C_LIO_LIThe basolateral amygdala (BLA) emerged as a key region displaying context- and time-dependent sex differences during early social interaction. C_LIO_LISex-specific BLA activity correlated with movement dynamics during investigation of isolated conspecifics, linking neural network activity to behavioural responses. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/727611v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@82f8a7org.highwire.dtl.DTLVardef@92d085org.highwire.dtl.DTLVardef@b7dc78org.highwire.dtl.DTLVardef@eb4dba_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Baicalin ameliorates behavioral and physiological deficits in Gtf2i-duplication mice and modulates synaptic activity in 7q11.23 Duplication Syndrome patient-derived neurons

7q11.23 Duplication Syndrome (7Dup) is a type of syndromic autism spectrum disorder caused by duplication of a typically 1.5-1.8 Mb segment in section q11.23 of chromosome 7, including 25-27 genes. Previous work has highlighted the GTF2I gene as playing a major role in the phenotype of 7Dup patients. Accordingly, mice with Gtf2i duplication (Gtf2i+/dup) are commonly used as an animal model of 7Dup. We previously reported deficits in several behavioral and physiological modalities, which were associated with Gtf2i dosage in mice conducting a battery of social discrimination tests. Here, we report the effect of treating Gtf2i+/dup mice with Baicalin, a naturally occurring flavonoid added to the mices drinking water (0.15 mg/ml), on these deficits. We found that Baicalin treatment ameliorated the higher surface temperature observed in Gtf2i+/dup males and the lower tail temperature observed in Gtf2i+/dup females during the social behavior tests. It also prevented the increased defecation rate exhibited by Gtf2i+/dup mice during the social preference test. We further analyzed the effect of Baicalin treatment on cortical neurons differentiated from 7Dup patient-derived IPSCs. Using whole cell patch clamp and calcium imaging, we found an increased rate of excitatory postsynaptic currents in Baicalin-treated cells, without a change in their firing rate, indicating a stronger synaptic activity in the Baicalin-treated cells. Altogether, our results reveal that Baicalin administration alleviates some of the behavioral and physiological effects of Gtf2i duplication in mice, and affects neuronal activity in cultured 7Dup human neurons. Thus, Baicalin administration has the potential to serve as a treatment for 7Dup patients.

neuroscience↗

bioRxiv2026

Oxytocin-dependent reorganization of social vs. food motivational hierarchy and corticostriatal neural activity by social isolation in rats

Animals must continuously prioritize among competing internal needs, yet the neural mechanisms that arbitrate between these drives remain poorly understood. Here, we used a behavioral paradigm in rats to quantify choice between social interaction and food seeking under varying need states. We show that social isolation selectively shifts preference toward social engagement, even under metabolic demand, indicating a reweighting of motivational priorities. Chronic local field potential recordings across prefrontal and striatal brain regions revealed that this shift is accompanied by a reconfiguration of corticostriatal theta-band coordination. Trial-by-trial analyses demonstrated that network dynamics predict behavioral choice, linking neural coordination to decision output. Pharmacological blockade of oxytocin receptors attenuated both the network reorganization and the behavioral prioritization shift, implicating oxytocin signaling in gating this process. Together, our findings identify a network-level mechanism through which internal states dynamically compete, providing a framework for understanding how the brain resolves conflicting motivational demands.

neuroscience↗

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↗

bioRxiv2025

Contrasting behavioral and physiological effects of Gtf2i duplication and deletion in mouse models of the 7q11.23 Duplication and Williams-Beuren Syndromes

7q11.23 Microduplication Syndrome (7Dup) and Williams-Beuren Syndrome (WBS) are two ASD-related syndromes characterized by both common and contrasting symptoms, caused by either duplication or deletion of a 1.5-1.8 Mb segment in section q11.23 of Human chromosome 7, respectively. Notably, WBS patients show reduced social fear and are considered hyper-social, while 7Dup patients suffer from social anxiety and withdrawal. Previous work suggests that the GTF2I gene, one of the genes included in this segment, has a major role in the social symptoms of both syndromes. Here, we combine video and thermal imaging in multiple social behavior tests to screen for behavioral and physiological variables showing variations in mice models with either a duplication (Gtf2i+/dup) or a deletion (Gtf2i+/del) of the gene. Our analyses of social behavior, micturition, and defecation patterns identify several differences between wild-type and mutant littermates, some of which show contrasting variations associated with Gtf2i dosage. Interestingly, thermal imaging revealed that Gtf2i dosage dictates the mices surface temperature profile during the tests, with Gtf2i+/dup males exhibiting higher surface temperature than their wild-type littermates, while Gtf2i+/del males and females show the opposite tendency. These results suggest that the two mouse models exhibit opposite changes in either their emotional state or thermoregulation capabilities, in correlation with Gtf2i dosage.

neuroscience↗

bioRxiv2024

Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex

The hypothalamic neuropeptide oxytocin is best known for its prosocial behavioral effects. However, the precise anatomical and cellular targets for oxytocin in the cortex during social behavior remain elusive. Here we show that oxytocin neurons project directly to the medial prefrontal cortex where evoked axonal oxytocin release facilitates social behaviors in adult female rats. In conjunction, we report that local oxytocin receptor-expressing (OTR+) cells are predominantly interneurons, whose activation promotes social interaction. Notably, this prosocial effect persists even under physiological challenge (hunger), pointing to a dedicated prosocial circuit capable of overriding primary survival drives. We further demonstrate that activation of these OTR+ interneurons inhibits principal cells specifically projecting to the basolateral amygdala, thus providing a putative mechanism of selective oxytocin action in this sociability-promoting cortical network.

neuroscience↗

bioRxiv2024

DeePosit: an AI-based tool for detecting mouse urine and fecal depositions from thermal video clips of behavioral experiments

In many mammals, including rodents, social interactions are often accompanied by active urination (micturition), which is considered a mechanism for spatial scent marking. Urine and fecal deposits contain a variety of chemosensory signals that convey information about the individuals identity, genetic strain, social rank, and physiological or hormonal state. Furthermore, scent marking has been shown to be influenced by the social context and by the individuals internal state and experience. Therefore, analyzing scent-marking behavior during social interactions can provide valuable insight into the structure of mammalian social interactions in health and disease. However, conducting such analyses has been hindered by several technical challenges. For example, the widely used void spot assay lacks temporal resolution and is prone to artifacts, such as urine smearing. To solve these issues, recent studies employed thermal imaging for the spatio-temporal analysis of urination activity. However, this method involved manual analysis, which is time-consuming and susceptible to observer bias. Moreover, defecation activity was hardly analyzed by previous studies. In the present study, we integrate thermal imaging with an open-source algorithm based on a transformer-based video classifier for automatic detection and classification of urine and fecal deposits made by male and female mice during various social behavior assays. Our results reveal distinct dynamics of urination and defecation in a test-, strain- and sex-dependent manner, indicating two separate processes of scent marking in mice. We validate this algorithm, termed by us DeePosit, and show that its accuracy is comparable to that of a human annotator and that it is efficient in various setups and conditions. Thus, the method and tools introduced here enable efficient and unbiased automatic spatio-temporal analysis of scent marking behavior in the context of behavioral experiments in small rodents.

animal behavior and cognition↗

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

Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing in Shank3-deficient rats

Social behaviors are crucial for human connection and belonging, often impacted in conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (VTA and NAc) plays a pivotal role in social behavior and is implicated in ASD. However, the impact of ASD-related mutations on social reward processing remains insufficiently explored. This study focuses on the Shank3 mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using the Shank3-deficient rat model. Our findings indicate that Shank3-deficient rats exhibit atypical social interactions and have difficulty adjusting behavior based on reward values, associated with modified neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, we demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects of Shank3 mutations on social reward and behavior, and identify a potential neural pathway for intervention.

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↗

bioRxiv2023

Simultaneous recording of ultrasonic vocalizations and sniffing from socially interacting individual rats using a miniature microphone

Vocalizations are pivotal in mammalian communication, especially in humans. Rodents accordingly rely on ultrasonic vocalizations (USVs) that reflect their internal state as a primary channel during social interactions. However, attributing vocalizations to specific individuals remains challenging, impeding internal state assessment. Rats emit 50 kHz USVs to indicate positive states and intensify sniffing during alertness and social interactions. Here, we present a method involving a miniature microphone attached to the rat nasal cavity that allows to capture both male and female individual rat vocalizations and sniffing patterns during social interactions. We found that while the emission of 50 kHz USVs increases during close interactions, these signals lack specific behavioral associations. Moreover, a previously unreported low-frequency vocalization type marking rat social interactions was uncovered. Finally, different dynamics of sniffing and vocalization activities point to distinct underlying internal states. Thus, our method facilitates the exploration of internal states concurrent with social behaviors. MotivationHere, we sought to solve the problem of identifying the emitter of a specific vocalization during free social interaction of animal models. The use of a miniature microphone carried by the subject and connected to its nasal cavity solved this challenge and allowed for assignment of any vocalization recorded during a social interaction to a specific individual. Moreover, the miniature microphone enabled simultaneous recording of sniffing and vocalization activities of an individual, thus facilitating recognition of the internal states underlying these traits.

animal behavior and cognition↗

bioRxiv2023

Ventral dentate gyrus-dominated LFP rhythmicity in the social brain reflects the context of social encounters

Mammalian social behavior is highly context-sensitive. Yet, little is known about the mechanisms that modulate social behavior according to its context. Recent studies have revealed a network of mostly limbic brain regions, here termed the "social brain", which regulates social behavior. We hypothesized that coherent theta and gamma rhythms reflect the organization of the social brain regions into functional networks in a context-dependent manner. To test this concept, we simultaneously recorded extracellular activity from multiple social brain regions in mice performing three social discrimination tasks. Local field potential (LFP) rhythmicity across all tasks was dominated by a general internal state. However, during stimulus investigation LFP rhythmicity was sensitive to stimulus characteristics. Specifically, the pattern of LFP coherence between the various regions reflected mainly the social context. Moreover, we found the ventral dentate gyrus to play a pivotal role in coordinating the context-specific rhythmic activity in the network.

neuroscience↗

bioRxiv2022

Cell types in the mouse amygdala and their transcriptional response to fear conditioning

The amygdala is one of the most widely studied regions in behavioral neuroscience. A plethora of classical, and new paradigms have dissected its precise involvement in emotional and social sensing, learning, and memory. Several important insights resulted from the use of genetic markers - yet, in the age of single cell transcriptomics, the amygdala remains molecularly underdescribed. Here, we present a molecular cell type taxonomy of the full mouse amygdala in fear learning and consolidation. We performed single-cell RNA-seq on naive and fear conditioned mice, inferred the 130 neuronal cell types distributions in silico using orthogonal spatial transcriptomic datasets, and describe the cell types transcriptional responses to learning and memory consolidation. Only a fraction of cells, within a subset of all neuronal types, were transcriptionally responsive to fear learning, memory and retrieval. These activated engram cells upregulated activity-response genes, and processes of synaptic signaling, plasticity, development and neurite outgrowth. Our transcriptome-wide data confirm known actors, and describe several new candidate genes. The atlas may help pinpoint the amygdalas circuits in performing emotional sensing and integration, and provide new insights to the global cellular processes involved.

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↗

bioRxiv2022

Oxytocin activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in-situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.

neuroscience↗

bioRxiv2021

Sex-dependent parameters of social behavior show marked variations between distinct laboratory mouse strains and their mixed offspring

BackgroundThe survival of individuals of gregarious species depends on their ability to properly form social interactions. In humans, atypical social behavior is a hallmark of several psychopathological conditions, such as depression and autism spectrum disorder, many of which have sex-specific manifestations. Various strains of laboratory mice are used to reveal the mechanisms mediating typical and atypical social behavior in mammals. MethodsHere we used three social discrimination tests (social preference, social novelty preference, and sex preference) to characterize social behavior in males and females of three widely used laboratory mouse strains (C57BL/6J, BALB/c, and ICR). ResultsWe found marked sex- and strain-specific differences in the preference exhibited by subjects in a test-dependent manner. Interestingly, we found some characteristics that were strain-dependent, while others were sex-dependent. Moreover, even in the social preference test, where both sexes of all strains prefer social over object stimuli, we revealed sex- and strain-specific differences in the behavioral dynamics. We then cross-bred C57BL/6J and BALB/c mice and demonstrated that the offspring of such cross-breeding exhibit a profile of social behavior which is different from both parental strains and depends on the specific combination of parental strains. ConclusionsWe conclude that social behavior of laboratory mice is highly sex- and strain-specific and strongly depends on genetic factors.

animal behavior and cognition↗

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↗

bioRxiv2020

Social recognition in rats and mice requires integration of olfactory, somatosensory and auditory cues

In humans, discrimination between individuals, also termed social recognition, can rely on a single sensory modality, such as vision. By analogy, social recognition in rodents is thought to be based upon olfaction. Here, we hypothesized that social recognition in rodents relies upon integration of olfactory, auditory and somatosensory cues, hence requiring active behavior of social stimuli. Using distinct social recognition tests, we demonstrated that adult male rats and mice do not recognize familiar stimuli or learn the identity of novel stimuli that are inactive due to anesthesia. We further revealed that impairing the olfactory, somatosensory or auditory systems prevents recognition of familiar stimuli. Finally, we found that familiar and novel stimuli generate distinct movement patterns during social discrimination and that subjects react differentially to the movement of these stimuli. Thus, unlike what occurs in humans, social recognition in rats and mice relies on integration of information from several sensory modalities.

animal behavior and cognition↗