Biology subjects

Christianson, J. P.

Publications and source records attributed to Christianson, J. P..

10 recordsLinked to original sources

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↗

bioRxiv2025

Pharmacological Modulation of MC4R in the Periaqueductal Gray Does Not Alter Social Behavior

Competing motivational drives are integral to survival and encompass a spectrum of internal physiological needs such as hunger to external goals like social connection. Elucidating how these motivational states interact at the neural level is critical to our understanding of adaptive behavior. Hunger-driven behaviors are primarily initiated by agouti-related peptide (AgRP), an inverse agonist of the melanocortin 4 receptor (MC4R), which acts to promote feeding by suppressing MC4R signaling. MC4R is present in the periaqueductal gray (PAG), a midbrain region involved in pain, appetite, and social behavior. A pilot study found a dense concentration of AgRP fibers in the PAG of male rats, suggesting a potential link between hunger-related signaling and social behavior in this region. To investigate the role of AgRP and MC4R in the PAG on social interaction, we conducted a within-subject dose-response experiment using male rats. Subjects received bilateral microinjections (0.5 {micro}L/side) of either vehicle, an MC4R agonist (THIQ), or an antagonist (HS014) into the PAG prior to a five-minute social exploration (SE) test with a novel juvenile conspecific. Contrary to our hypothesis, pharmacological manipulation of MC4R activity in the PAG did not produce significant changes in social interaction time, suggesting that MC4R in the PAG may not directly play a major role in modulating social behavior in rodents. These results highlight the complexity of the neural circuitry involved in social motivation, hunger, and other competing motivational states.

neuroscience↗

bioRxiv2023

Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex

RationaleIn a social context, individuals are able to detect external information from others and coordinate behavioral responses according to the situation, a phenomenon called social decision-making. Social decision-making is multifaceted, influenced by emotional and motivational factors like stress, sickness and hunger. However, the neurobiological basis for motivational state competition and interaction are not well known. ObjectiveWe investigated possible neural mechanisms through which internal states could shape social behavior in a social affective preference (SAP) test. In the SAP test, experimental rats given a choice to interact with naive or stressed conspecifics exhibit an age-dependent preference to interact with stressed juvenile conspecifics, but avoid stressed adult conspecifics. First, we assessed the effect of hunger on SAP behavior. Behavior in the SAP test requires the insular cortex, which receives input from the hunger-related peptides melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus (LH). This study aimed to evaluate the role of LH and insular MCH and orexin in SAP test. MethodsSAP tests were conducted in rats that were sated, food deprived or allowed 1 h of access to food after 14 h of deprivation (relieved condition). Separate cohorts of sated rats received cannula implants for microinjection of drugs to inhibit the LH or to block or stimulate MCH or orexin receptors in the insula prior to SAP tests or social interaction tests. ResultsFood and water deprivation prior to SAP tests with juvenile rats caused a shift in preference away from the stressed rat toward the naive juveniles. Pharmacological inhibition of LH with muscimol (100 ng/side) abolished the preference for the juvenile stressed conspecific, as well as the preference for the adult naive conspecific. The blockade of MCHr1 or orexin receptors in the insular cortex with SNAP94847 (50{micro}M) or TCS1102 (1{micro}M), respectively, also abolished the preference for the stressed juvenile conspecific, but only the antagonism of orexin receptors was able to abolish the preference for the adult naive conspecific. Microinjection of increasing doses (50 or 500 nM) of MCH or orexin-A in the insular cortex increased the interaction time in the one-on-one social interactions test with juvenile conspecifics, however only the microinjection of orexin-A increased the interaction time with adult naive conspecifics. ConclusionsTaken together, these results suggest that lateral hypothalamus peptides shape the direction of social approach or avoidance via actions MCH and orexin neurotransmission in the insular cortex.

neuroscience↗

bioRxiv2023

Serotonin modulates social responses to stressed conspecifics via insular 5-HT2C receptors in rat

Social interaction allows for the transfer of affective states among individuals, and the behaviors and expressions associated with pain and fear can evoke anxiety-like states in observers which shape subsequent social interactions. We hypothesized that social reactions to stressed individuals engage the serotonergic dorsal raphe nucleus (DRN) which promotes anxiety-like behavior via postsynaptic action of serotonin at serotonin 2C (5-HT2C) receptors in the forebrain. First, we inhibited the DRN by administering an agonist (8-OH-DPAT, 1{micro}g in 0.5{micro}L) for the inhibitory 5-HT1A autoreceptors which silences 5-HT neuronal activity via G-protein coupled inward rectifying potassium channels. 8-OH-DPAT prevented the approach and avoidance, respectively, of stressed juvenile (PN30) or stressed adult (PN60) conspecifics in the social affective preference (SAP) test in rats. Similarly, systemic administration of a 5-HT2C receptor antagonist (SB242084, 1mg/kg, i.p.) prevented approach and avoidance of stressed juvenile or adult conspecifics, respectively. Seeking a locus of 5-HT2C action, we considered the posterior insular cortex which is critical for social affective behaviors and rich with 5-HT2C receptors. SB242084 administered directly into the insular cortex (5{micro}M in 0.5{micro}L bilaterally) interfered with the typical approach and avoidance behaviors observed in the SAP test. Finally, using fluorescent in situ hybridization, we found that 5-HT2C receptor mRNA (htr2c) is primarily colocalized with mRNA associated with excitatory glutamatergic neurons (vglut1) in the posterior insula. Importantly, the results of these treatments were the same in male and female rats. These data suggest that interactions with stressed others require the serotonergic DRN and that serotonin modulates social affective decision-making via action at insular 5-HT2C receptors.

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↗

bioRxiv2022

Maternal immune activation alters social affective behavior and sensitivity to corticotropin releasing factor in male but not female rats

Prenatal infection increases risk for neurodevelopmental disorders such as autism in offspring. In the rodents, prenatal administration of the viral mimic Polyinosinic:polycytidylic acid (Poly I:C) allows for investigation of developmental consequences of gestational sickness on offspring social behavior and neural circuit function. Because maternal immune activation (MIA) disrupts cortical development and sociability, we examined social decision-making in a rat social affective preference (SAP) task. Following Poly I:C (0.5 mg/kg) on gestational day 12.5, male adult offspring (PN 50) exhibited atypical social interactions with stressed conspecifics whereas female SAP behavior was unaffected by maternal Poly I:C. Social responses to stressed conspecifics depend upon the insular cortex where corticotropin releasing factor (CRF) modulates synaptic transmission and SAP behavior. We characterized insular field excitatory postsynaptic potentials (fEPSP) in adult offspring of MIA or control treated dams. Male MIA offspring showed decreased sensitivity to CRF (300 nM) while female MIA offspring showed greater sensitivity to CRF compared to sham offspring. These sex specific effects appear to be behaviorally relevant as CRF injected into the insula of male and female rats prior to social exploration testing had no effect in MIA male offspring but increased social interaction in female MIA offspring. We examined the cellular distribution of CRF receptor mRNA but found no effect of maternal Poly I:C in the insula. Together these experiments reveal sex specific effects of prenatal infection on offspring social decision making and identify insular CRF signaling as a novel neurobiological substrate for autism risk.

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↗