Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments

Abstract

SUMMARY The striatum contains neurochemically defined compartments termed patches and matrix. Previous studies suggest patches preferentially receive limbic inputs and project to dopamine neurons in substantia nigra (SNc), whereas matrix neurons receive sensorimotor inputs and do not innervate SNc. Using BAC-Cre transgenic mice with viral tracing techniques we mapped brain-wide differences in the input-output organization of the patch/matrix. Findings reveal a displaced population of striatal patch neurons termed “exo-patch”, which reside in matrix zones but have neurochemistry, connectivity, and electrophysiological characteristics resembling patch neurons. Contrary to previous studies, results show patch/exo-patch and matrix neurons receive both limbic and sensorimotor information. A novel inhibitory projection from bed nucleus of the stria terminalis to patch/exo-patch neurons was revealed. Projections to SNc were found to originate from patch/exo-patch and matrix neurons. These findings redefine patch/matrix beyond traditional neurochemical topography and reveal new principles about their input-output connectivity, providing a foundation for future functional studies.

Topographic precision in sensory and motor corticostriatal projections varies across cell type and cortical area

“…Targeting of afferents to distinct striatal compartments such as patch and matrix may also differ between different cortical areas, though average sensorimotor populations target both patch and matrix neurons in similar proportions 56 . Afferents from both IT- and PT-type cells form connections to direct and indirect-pathway SPNs 57 .…”

Striosome-based map of the mouse striatum that is conformable to both cortical afferent topography and uneven distributions of dopamine D1 and D2 receptor-expressing cells

“…Because information regarding the actual positions of these divisions is not currently available, they are only conceptually presented in schematic images of the striatum. Thus, even researchers using the newest technologies still do not have a common reference map that can be shared with others to facilitate mutual understanding of experimental data such as site-specific expression of genes (Tai et al 2013), virus-mediated detailed connectivity (Fujiyama et al 2011; Wall et al 2013; Smith et al 2016), and responses to channel-gating light with an illuminating apparatus placed in the brains of behaving animals (Valjent et al 2009; Friedman et al 2015; Smith et al 2016; Stephenson-Jones et al 2016; Bloem et al 2017). …”

Striatal Local Circuitry: A New Framework for Lateral Inhibition

“…Afferents to patch and matrix are also thought to arise from different sources with patches receiving limbic inputs and matrix neurons receiving sensorimotor inputs (Gerfen, 1984). However recent viral tracing methods have cast doubt on this strict segregation (Smith et al, 2016). …”

“…Another novel inhibitory projection from the bed nucleus of the stria terminalis to the striatum has also been described, terminating on patch and exo-patch SPNs in the dorsal striatum (Smith et al, 2016). Using tract tracing, another study identified an extrinsic source of acetylcholine arising from brainstem nuclei, the pedunculopontine nucleus and the lateral dorsal tegmental nucleus (Dautan et al, 2014).…”