Projection-Specific Potentiation of Ventral Pallidal Glutamatergic Outputs after Abstinence from Cocaine.

The ventral pallidum (VP) is a central node in the reward system that is strongly implicated in reward and addiction. Although the majority of VP neurons are GABAergic and encode reward, recent studies revealed a novel glutamatergic neuronal population in the VP [VP neurons expressing the vesicular glutamate transporter 2 (VPVGluT2)], whose activation generates aversion. Withdrawal from drugs has been shown to induce drastic synaptic changes in neuronal populations associated with reward, such as the ventral tegmental area (VTA) or nucleus accumbens neurons, but less is known about cocaine-induced synaptic changes in neurons classically linked with aversion. Here, we demonstrate that VPVGluT2 neurons contact different targets with different intensities, and that cocaine conditioned place preference (CPP) training followed by abstinence selectively potentiates their synapses on targets that encode aversion. Using whole-cell patch-clamp recordings combined with optogenetics in male and female transgenic mice, we show that VPVGluT2 neurons preferentially contact aversion-related neurons, such as lateral habenula neurons and VTA GABAergic neurons, with minor input to reward-related neurons, such as VTA dopamine and VP GABA neurons. Moreover, after cocaine CPP and abstinence, the VPVGluT2 input to the aversion-related structures is potentiated, whereas the input to the reward-related structures is depressed. Thus, cocaine CPP followed by abstinence may allow VPVGluT2 neurons to recruit aversion-related targets more readily and therefore be part of the mechanism underlying the aversive symptoms seen after withdrawal.SIGNIFICANCE STATEMENT The biggest problem in drug addiction is the high propensity to relapse. One central driver for relapse events is the negative aversive symptoms experienced by addicts during withdrawal. In this work, we propose a possible mechanism for the intensification of aversive feelings after withdrawal that involves the glutamatergic neurons of the ventral pallidum. We show not only that these neurons are most strongly connected to aversive targets, such as the lateral habenula, but also that, after abstinence, their synapses on aversive targets are strengthened, whereas the synapses on other rewarding targets are weakened. These data illustrate how after abstinence from cocaine, aversive pathways change in a manner that may contribute to relapse.

Having Siblings is Associated with Better Social Functioning in Autism Spectrum Disorder.

Sibling relationships play a unique developmental role, especially in emotional and social domains. In autism spectrum disorder (ASD), social-communication skills are often impaired in comparison to typical development. Therefore, studying siblings' effects on social skills of the child with ASD is important. This retrospective study examined how autism severity and functioning were affected by having older and younger sibling/s, the sex of the index child and of the sibling, and the number of siblings. The study population included 150 participants with ASD (mean age = 4:0 ± 1:6), divided into three equal groups (no sibling, older and younger siblings), matched for cognitive level. The evaluation included neurological and standardized behavioral, cognitive, and functional assessments. Children with ASD with older siblings showed less severe social interaction deficits and better social adaptive skills than only children. No significant differences in autism severity and adaptive functioning were noted between the group with younger siblings and the other groups. The more older siblings the affected child had, the better their social functioning. The sex of the participants with ASD and that of the sibling were not associated with social functioning. Social interaction deficits, the presence of older or younger siblings for children with ASD, and higher cognitive ability contributed significantly to the explained variance (48.9%) in social adaptive skills. These findings emphasize that older siblings positively influence the social skills of their younger sibling with ASD. The effect of typically developing younger siblings was modest and seen only in children with ASD and better cognition.