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...

Elevation of brain magnesium enhances synaptic plasticity and extinction of conditioned fear memories. This experiment examined the generalizability of this phenomenon by studying the effects of a novel magnesium compound, magnesium-L-threonate (MgT), on conditioned taste aversion (CTA) extinction and spontaneous recovery (SR). Adult male Sprague-Dawley rats were maintained on a 23-hour water deprivation cycle and acquired a CTA following the taste of a CS [0.3% saccharin + 16mg/ml MgT (SAC+MgT)] paired with a US [81 mg/kg (i.p.) Lithium Chloride (LiCl)]. Following CTA acquisition, rats drank a water + MgT solution for up to 1 hour/day over the next 31 days. For 14 additional days, some animals continued water + MgT treatment, but others drank water only to allow MgT to be eliminated from the body. We then employed 2 different extinction paradigms: (1) CS-Only (CSO), in which SAC was presented, every-other day, or (2) Explicitly Unpaired (EU), in which both SAC and LiCl were presented, but on alternate days. EU extinction procedures have been shown to speed CTA extinction and reduce spontaneous recovery of the aversion. Throughout extinction, half of the rats in each group continued to drink MgT (now in SAC or supplemental water+MgT solution), whereas the other half drank SAC only/water only until SAC drinking reached ≥ 90% of baseline (asymptotic extinction). Rats receiving MgT just before/during extinction drank less SAC on the first day of extinction suggesting that they had retained a stronger CTA. MgT enhanced the rate of extinction. Furthermore, the MgT-treated rats showed a relatively modest SR of the CTA 30 days later – indicating that the extinction procedure was more effective for these animals. Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion.

The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning. Therefore, the current study investigated the effects of ketamine (an NMDA receptor blocking drug) on both a conditioned taste aversion (CTA) and latent inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought to determine if a CTA could be diminished by nonreinforced preexposure to a CS in fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100% allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received a second injection of the CS, followed by either lithium chloride (the US) or saline. Finally, on E21 pups received oral lavage with allicin and observations of ingestive orofacial motor responses were recorded. When allicin had been paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of orofacial movements, indicative of an aversion to this taste. Preexposure to the garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted the formation of the CTA and had some impact on LI. However, the direct effect of ketamine on LI is less certain since the drug also blocked the original CTA.

Due to its relevance to clinical practice, extinction of learned fears has been a major focus of recent research. However, less is known about the means by which conditioned fears re-emerge (i.e., spontaneously recover) as time passes or contexts change following extinction. The periaqueductal gray represents the final common pathway mediating defensive reactions to fear and we have reported previously that the dorsolateral PAG (dlPAG) exhibits a small but reliable increase in neural activity (as measured by c-fos protein immunoreactivity) when spontaneous recovery (SR) of a conditioned taste aversion (CTA) is reduced. Here we extend these correlational studies to determine if inducing dlPAG c-fos expression through electrical brain stimulation could cause a reduction in SR of a CTA. Male Sprague-Dawley rats acquired a strong aversion to saccharin (conditioned stimulus; CS) and then underwent CTA extinction through multiple non-reinforced exposures to the CS. Following a 30-day latency period after asymptotic extinction was achieved; rats either received stimulation of the dorsal PAG (dPAG) or stimulation of closely adjacent structures. Sixty minutes following the stimulation, rats were again presented with the saccharin solution as we tested for SR of the CTA. The brain stimulation evoked c-fos expression around the tip of the electrodes. However, stimulation of the dPAG failed to reduce SR of the previously extinguished CTA. In fact, dPAG stimulation caused rats to significantly suppress their saccharin drinking (relative to controls) – indicating an enhanced SR. These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs.