Functionally Distinct Connectivity of Developmentally Targeted Striosome Neurons

Abstract

Summary: One long-standing model of striatal function divides the striatum into compartments called striosome and matrix. While some anatomical evidence suggests that these populations represent distinct striatal pathways with differing inputs and outputs, functional investigation has been limited by the methods for identifying and manipulating these populations. Here, we utilize hs599CreER mice as a new tool for targeting striosome projection neurons and testing their functional connectivity. Extending anatomical work, we demonstrate that striosome neurons receive greater synaptic input from prelimbic cortex, whereas matrix neurons receive greater input from primary motor cortex. We also identify functional differences in how striosome and matrix neurons process excitatory input, providing the first electrophysiological method for delineating striatal output neuron subtypes. Lastly, we provide the first functional demonstration that striosome neurons are the predominant striatal output to substantia nigra pars compacta dopamine neurons. These results identify striosome and matrix as functionally distinct striatal pathways. : McGregor et al. utilize a novel transgenic mouse line to dissect the functional circuitry and electrophysiology of striatal striosome and matrix neurons. They report that striosome and matrix neurons receive distinct synaptic input and that striosome neurons represent the major striatal population innervating substantia nigra pars compacta dopamine neurons. Keywords: striosome, dopamine, patch, matrix, striatum, prelimbic, primary motor, hs599, electrophysiology