Biology subjects

Djerdjaj, A.

Publications and source records attributed to Djerdjaj, A..

7 recordsLinked to original sources

bioRxiv2026

Adolescent blockade of complement signaling in the lateral septum increases social novelty seeking behavior in male mice

Social behaviors are critical for survival and change dramatically over the lifespan. Adolescence is a critical period of development during which social novelty seeking peaks before declining into adulthood. Adolescence is also a time of pronounced neural circuit refinement as excess synapses are eliminated. One critical mechanism supporting this maturation of neural circuits is microglial pruning of synapses through the classical complement signaling cascade. However, it remains unclear how microglial pruning of the neural circuitry supporting social novelty preference shapes the trajectory of this behavior during adolescence. To address this, we blocked microglial complement-dependent pruning during adolescence by injecting neutrophil inhibitory factor (NIF; blocks the adhesion of ligands to CD11b/C3 receptor) in the lateral septum (LS), a key node in the social circuitry supporting social novelty preference, in male mice. We found that NIF administration into the LS during adolescence increased preference for the novel social chamber over the familiar as compared to control PBS administration. LS-NIF treatment had no impact on anxiety-like behavior in the light-dark box test and no effect on sociability. LS-NIF treatment also decreased the expression of immune-related genes in the LS as compared to PBS treatment. These data support the hypothesis that complement-dependent microglial synaptic elimination in the LS is critical for the developmental progression of social novelty preference.

neuroscience↗

bioRxiv2025

Insular input to the prelimbic cortex underlies social affective behavior in rats.

To navigate social interactions, animals must adjust their behavior in response to information derived from conspecifics. The integration of social information and coordination of behavior occurs within a distributed social decision making network. The prelimbic (PL) prefrontal cortex and the insula (IC) are key nodes in the salience network which is anatomically situated to interact with the social brain. We investigated the IC-PL circuit in a social affective preference (SAP) test in which subject rats are exposed to 2 age-matched conspecifics where one is stressed via footshock and the other is naive to stress. Typically, rats approach stressed juvenile conspecifics but avoid stressed adults. Using a combination of local and tract specific loss of function methods, we demonstrate that the PL, anterior IC, and the tracts between the posterior or anterior IC and the PL are necessary when rats face the choice to approach or avoid stressed conspecifics. Going further, chemogenetic inhibition of PL neurons innervated by the IC also interfered with social affective behaviors. These studies enrich our understanding of the neurobiology of social decision making by establishing a mechanistic link between insular and prefrontal circuits. Significance StatementThe successful navigation of social interactions requires detection of the emotional states of others and the appropriate behavioral output. While the insula and prefrontal cortex have both been implicated as key brain regions in social decision-making and the salience network, their functional role in guiding social behaviors are largely unknown. Using a combination of region-specific and circuit manipulations in rats, we present evidence of the necessity of the insula-prefrontal pathway in the approach and avoidance of stressed others, reinforcing the importance of this cortical system in social affective processing. This work provides new insight into the network-level mechanisms underlying social behavior and highlights an important circuit that may be relevant to understanding neuropsychiatric disorders with social impairments.

neuroscience↗

bioRxiv2023

Social affective behaviors among female rats involve the basolateral amygdala and insular cortex

The ability to detect, appraise, and respond to anothers emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5L saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.

neuroscience↗

bioRxiv2021

Insular cortex corticotropin-releasing factor integrates stress signaling with social decision making.

Impairments in social cognition manifest in a variety of psychiatric disorders, making the neurobiological mechanisms underlying social decision making of particular translational importance. The insular cortex is consistently implicated in stress-related social and anxiety disorders, which are associated with diminished ability to make and use inferences about the emotions of others to guide behavior. We investigated how corticotropin releasing factor (CRF), a neuromodulator evoked by both self and social stressors, influenced the insula. In acute slices from male and female rats, CRF depolarized insular pyramidal neurons. In males, but not females, CRF suppressed presynaptic GABAergic inhibition leading to greater excitatory synaptic efficacy in a CRF receptor 1 (CRF1) and cannabinoid receptor 1 (CB1) dependent fashion. In males only, insular CRF increased social investigation, and CRF1 and CB1 antagonists interfered with social decision making. To investigate the molecular and cellular basis for the effect of CRF we examined insular CRF1 and CB1 mRNAs and found greater total insula CRF1 mRNA in females but greater CRF1 and CB1 mRNA colocalization in male insular cortex glutamatergic neurons which suggest complex, sex-specific organization of CRF and endocannabinoid systems. Together these results reveal a new sex-specific mechanism by which stress and affect contribute to social decision making.

neuroscience↗

bioRxiv2019

DeepLabCut Analysis of Social Novelty Preference

The description and quantification of social behavior in laboratory rodents is central to basic and translational research. Conventional ethological approaches to social behavior are fraught with challenges including bias, significant human effort and temporal accuracy. Here we show proof of principle that machine learning can be applied to laboratory tests of social decision making. Rats underwent social novelty preference tests which were scored both by hand and again by a convolutional neural network generated in the DeepLabCut computer vision package of Mathis and colleagues. The CNN generated temporally (30Hz) and locally (<5pixels) accurate identification of rat nose, eye and ear positions which were then used to compute social interaction and topography heat maps. In sum, hand- and computer-scoring were strongly correlated, and each identified significant preferences to interact with novel conspecifics which sets the stage for applying DeepLabCut analysis to other types of social interaction in the future.

animal behavior and cognition↗

bioRxiv2019

Insular cortex projections to nucleus accumbens core mediate social approach to stressed juvenile rats

Social interactions are shaped by features of the interactants including age, emotion, sex and familiarity. Age-specific responses to social affect are evident when an adult male rat is presented with a pair of unfamiliar male conspecifics, one of which is stressed via 2 footshocks and the other naive to treatment. Adult test rats prefer to interact with stressed juvenile (PN30) conspecifics, but avoid stressed adult (PN50) conspecifics. This pattern depends upon the insular cortex (IC) which is anatomically connected to the nucleus accumbens core (NAc). The goal of this work was to test the necessity of IC projections to NAc during social affective behavior. Here, bilateral pharmacological inhibition of the NAc with tetrodotoxin (1{micro}M; 0.5ul/side) abolished the preference for stressed PN30, but did not alter interactions with PN50 conspecifics. Using a combination of retrograding tracing and c-Fos immunohistochemistry, we report that social interactions with stressed PN30 conspecifics elicit greater Fos immunoreactivity in IC [->] NAc neurons than interactions with naive PN30 conspecifics. Chemogenetic stimulation of IC terminals in the NAc increased social exploration with juvenile, but not adult, conspecifics, while chemogenetic inhibition of this tract blocked the preference to investigate stressed PN30 conspecifics, which expands upon our previous finding that optogenetic inhibition of IC projection neurons mediated approach and avoidance. These new findings suggest that outputs of IC to the NAc modulate social approach, which provides new insight to the neural circuitry underlying social decision-making. Significance StatementSocial decision-making underlies an animals behavioral response to others in a range of social contexts. Previous findings indicate the insular cortex (IC) and the nucleus accumbens (NAc) play important roles in a range of social behaviors, and human neuroimaging implicates both IC and NAc in autism and other psychiatric disorders characterized by aberrant social cognition. To test whether IC projections to the NAc are involved in social decision making, circuit-specific chemogenetic manipulations demonstrated that the IC [->] NAc pathway mediates social approach toward distressed juvenile, but not adult, conspecifics. This finding is the first to implicate this circuit in rodent socioemotional behaviors and may be a neuroanatomical substrate for integration of emotion with social reward.

neuroscience↗

bioRxiv2018

Familiarity modulates social approach toward stressed conspecifics in female rats

Familiarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naive and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.

animal behavior and cognition↗