Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons in male mice

Abstract

The medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity in acute brain slices. We show that in male mice, mPFC neurons that project to the basolateral amygdala (BLA) display unique spatial patterns of local-circuit synaptic connectivity, which distinguish them from the general mPFC cell population. When considering synaptic connections between pairs of mPFC neurons, the intrinsic properties of the postsynaptic cell and the anatomical positions of both cells jointly account for ~7.5% of the variation in the probability of connection. Moreover, anatomical distance and laminar position explain most of this fraction in variation. Our findings reveal the factors determining connectivity in the mPFC and delineate the architecture of synaptic connections in the BLA-projecting subnetwork.

Abstract

Little is known about the synaptic organization of associative cortical structures such as the medial prefrontal cortex. Here, the authors use two-photon optogenetic stimulation to obtain a detailed cellular resolution map of functional synaptic connectivity of the mouse medial prefrontal cortex, finding unique spatial patterns of local-circuit connectivity in neurons that project to the basolateral amygdala.