Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Abstract

Social animals detect the affective states of others and utilize this information to orchestrate appropriate social interactions. Social affective behaviors include cooperation, reproductive acts and avoiding sick individuals. In a social affective behavioral test in which experimental adult male rats were given the choice to interact with either naive or stressed conspecifics, the experimental rats demonstrated both approach and avoidant behaviors towards the conspecific, depending upon the age of the conspecific; experimental adult rats approached the stressed juvenile but avoided the stressed adult. Optogenetic inhibition of the insular cortex, a region anatomically positioned to contribute to social cognition, disrupted these behaviors. Receptors for the social nonapeptide oxytocin (OT) are found in high density within the insular cortex and here oxytocin increased intrinsic excitability and synaptic efficacy in acute insular cortex slices. Blockade of oxytocin receptors (OTRs) in the insula eliminated the effect of conspecific stress on approach behavior, while insular administration of OT recapitulated the behaviors typically observed in response to stressed conspecifics. Network analysis using Fos immunoreactivity identified functional connectivity between the insular cortex and the network of regions involved in social decision making. These results implicate insular cortex as a novel target of OT and suggest that insula is a key component in the circuit underlying age-dependent social responses to stressed conspecifics.Social animals, including humans, have an enormous repertoire of behavioral expressions that provide for the transmission of one's affective state to other members of the group 1-3 . Sensory and perceptive systems in the "social decision-making network" (SDMN) which consists of the social brain network 4 and the mesolimbic reward system 5 allow one to appraise these social stimuli and integrate them with past experiences, situational, and somatic factors to shape specific behavioral responses 6 . In addition to the SDMN, growing evidence implicates insular cortex in responding to socioemotional stimuli in humans. When tasked to identify the emotion of another from a facial expression, or to observe another suffer a painful stimulation, a reliable neural correlate is relative increase in the blood oxygen level dependent (BOLD) signal in the insular cortex 7,8 . Accordingly, emotion recognition and empathic deficits have been reported among individuals with insular cortex lesions [9][10][11][12] . Empathic processes are also disrupted in autism spectrum 1 Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA 2 These authors made equal contributions to this work. *Corresponding Author: John P. Christianson, Department of Psychology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467 USA, Email: j.christianson@bc.edu, Phone: +1-617-552-3970.A note about the preprint. This manuscript was submitted to bioRxiv.org after multiple rounds of peer review. The manuscrip...

Familiarity modulates social approach toward stressed conspecifics in female rats

“…Experimental observer rats were free to interact with either of the targets. Consistent with other observations [8, 9] experimental adult rats avoided stressed conspecifics [31]. Notably, these observations were made in unfamiliar groups of rats.…”

“…As described previously [31], the SAP test allows for the quantification of social exploration of an experimental rat directed toward 2 target conspecifics, 1 naïve to treatment and the other stressed. The SAP test began with 2 days of habituation: experimental rats were acclimated to the test area, a clear plastic cage (50 × 40 × 20cm, L × W × H) with a wire lid, for 60 min and then presented 2 empty restraint chambers (day 1) or 2 naive conspecifics (day 2) housed in the restraint chambers (see Fig.…”

“…Immobility is expressed in states of fear or anxiety [33], self-grooming may reflect emotion contagion [23] and biting and pulling may reflect aggression. The behavior of target rats was not quantified; interested readers are directed to our prior work for this analysis [31].…”

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

“…The insula has been implicated in many studies of depression examining functional connectivity, volumetric analyses and biomarkers for treatment outcomes 32 . The insula is also involved in emotion processing, self-awareness and motor control 33 and also specifically in anticipatory cues and approach and avoidance behavior 34, 35 . As with the precuneus, reduced insula may indicate a biological mechanism whereby reduced activity during avoidance of negative stimuli could increase exposure to negative events and therefore more anhedonic symptoms.…”

A whole-brain connectivity map of mouse insular cortex

“…Rodent studies further demonstrated roles for the IC in multisensory (Gogolla, Takesian, Feng, Fagiolini, & Hensch, 2014; Rodgers, Benison, Klein, & Barth, 2008) and pain processing (Tan et al, 2017), representation of valence (Wang et al, 2018), learning and memory (Bermúdez-Rattoni, Okuda, Roozendaal, & McGaugh, 2005; Lavi, Jacobson, Rosenblum, & Lüthi, 2018), social interactions (Rogers-Carter et al, 2018), gustation (Peng et al, 2015; Wang et al, 2018), drug cravings and malaise (Contreras, Ceric, & Torrealba, 2007), and aversive states such as hunger, thirst, and anxiety (Gehrlach et al, 2019; Livneh et al, 2017, 2020).…”