Function of thalamic excitatory synapses in social reward processing



 DESCRIPTION (provided by applicant): It is fast becoming clear that symptoms of psychiatric disorders, such as social avoidance, which are present in multiple conditions, may have singular neural dysfunctions underlying their presentation. Social abnormalities are present in autism, schizophrenia, depression and anxiety-related disorders, representing a significant portion of the population afflicted with mental disease. While many pharmacotherapies exist, the success rate of treating a majority of patients is surprisingly low. This highlights the urgency in studyin common symptoms across multiple models, while examining new brain circuits to parse out specific adaptations responsible for maladaptive behaviors. While the brain's dopamine system is clearly involved in psychiatric disorders, the brain's major neurotransmitter glutamate has also recently been implicated in underlying certain psychiatric symptoms, yet due to its ubiquity throughout the brain, its function has been difficult to determine. Many studies of the effects of stress on the brain have seen that it alters cell morphology and electrical properties, however many of these studies have occurred in discrete brain regions without knowledge of the input to the cell. With the advent of novel viral techniques and transgenic mouse lines it is now possible to isolate specific synapses, the point of communication between cells, to discover which glutamatergic pathways are involved in a specific behavior. In this proposal I will utilize two stress paradigms (a social and non-social) to isolate the effects of social stress on social reward processing. I will utilize manipulation of specific cells with light-activated ion channels and transgenic lines in combination with electrophysiology to study glutamatergic synapses of the thalamus impinging upon regions important in reward processing and social behavior, specifically the prefrontal cortex and nucleus accumbens. This proposal hypothesizes that social stress will have unique synaptic adaptations when compared to non-social stress and these adaptions are specifically involved in regulating social reward processing. Preliminary results demonstrate the involvement of thalamic cells synapsing on nucleus accumbens neurons in social interaction and the impaired acquisition of a social conditioned-place preference selectively by social stress. This study will seek to further understand how altering activity at these synapses can alleviate stress induced impairments in social behavior, as well as examining other thalamic based circuits that may regulate social behavior. The information gathered from these studies will provide novel starting points for developing unique therapies to alter circuit function and alleviate specific symptoms of psychiatric disorders.