High-resulution and cell-type-specific mapping of synaptic circuit organization in the bed nucleus of the stria terminalis

University Of California-Irvine, Irvine CA

Investigators

Linked publications & trials

Abstract

Project Summary / Abstract The bed nucleus of the stria terminalis (BNST) plays a central role in the normal adaptive response to stress, and has been implicated in general anxiety disorders, posttraumatic stress disorder (PTSD) and stress-induced drug abuse. Most existing knowledge about intrinsic and extrinsic BNST circuit connections is derived from classic anatomical studies which do not reveal functional synaptic connections. Due to previous technical limitations, many aspects of the intrinsic circuitry and local circuit organization of synaptic inputs in the BNST are not well understood. We propose to apply recent technological advancements in genetic cell targeting and photostimulation-based circuit mapping to build a high resolution functional map of the synaptic circuit organization of specific BNST neuron types. We hypothesize that strong local inhibitory connections are a major organizational principle in the anterior dorsal BNST, and that the relative balance of local BNST inhibitory synaptic connections underlies functional interactions between the anxiolytic and anxiogenic promoting subregions. To test this hypothesis, in Specific Aim1, we will use laser scanning photostimulation to map local synaptic input connections to three non-overlapping neuron types in the anterior dorsal BNST, including non- GABAergic CaMKII? expressing neurons, GABAergic somatostatin-expressing (SOM) and corticotropin- releasing hormone expressing (CRH) neurons. In Specific Aim 2, we will complement and extend laser scanning photostimulation studies with optogenetic stimulation-based circuit mapping to analyze inputs from specific neuronal subsets within the local BNST circuits. If successfully implemented, the proposed studies will lead to important progress toward understanding cell-type based local BNST circuit organization and function.