Abstract
The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout the BG, thalamus and cortex. Ongoing work seeks to map axonal projection patterns from GP cell types, as defined by their electrophysiological and molecular properties. Here we use transgenic mice and recombinant viruses to characterize parvalbumin expressing (PV+) GP neurons within the BG circuit. We confirm that PV+ neurons 1) make up ~40% of the GP neurons 2) exhibit fast-firing spontaneous activity and 3) provide the major axonal arborization to the STN and substantia nigra reticulata/compacta (SNr/c). PV+ neurons also innervate the striatum. Retrograde labeling identifies ~17% of pallidostriatal neurons as PV+, at least a subset of which also innervate the STN and SNr. Optogenetic experiments in acute brain slices demonstrate that the PV+ pallidostriatal axons make potent inhibitory synapses on low threshold spiking (LTS) and fast-spiking interneurons (FS) in the striatum, but rarely on spiny projection neurons (SPNs). Thus PV+ GP neurons are synaptically positioned to directly coordinate activity between BG input nuclei, the striatum and STN, and thalamic-output from the SNr.
Highlights
The basal ganglia (BG) are interconnected forebrain nuclei necessary for selecting and shaping motor and cognitive behaviors
This subdivision is the basis for the prominent model explaining how the BG control cortical feedback and behavior[5,6]: direct pathway spiny projection neurons (SPNs) promote actions by disinhibiting the thalamus and cortex, whereas indirect pathway SPNs SPNs dampen or sculpt actions by indirectly disinhibiting the SNr and potentiating BG inhibitory outputs
We sought to understand how PV+ globus pallidus externus (GP) neurons fit into a cell-type based model of BG circuits, using transgenic mice and recombinant viruses to selectively label and light-activate this neuronal population
Summary
The basal ganglia (BG) are interconnected forebrain nuclei necessary for selecting and shaping motor and cognitive behaviors. The diversity and function of BG cell types is best understood in the striatum, which contains spiny projection neurons (SPNs) and a handful of distinct interneuron types[1]. Based on axonal projections[2], electrophysiological properties[3] and dopamine receptor expression[4], SPNs fall into two major categories. This subdivision is the basis for the prominent model explaining how the BG control cortical feedback and behavior[5,6]: direct pathway SPNs (dSPNs) promote actions by disinhibiting the thalamus and cortex, whereas indirect pathway SPNs SPNs (iSPNs) dampen or sculpt actions by indirectly disinhibiting the SNr and potentiating BG inhibitory outputs.
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