Excitatory extrinsic afferents to striatal interneurons and interactions with striatal microcircuitry

Abstract

The striatum constitutes the main input structure of the basal ganglia and receives two major excitatory glutamatergic inputs, from the cortex and the thalamus. Excitatory cortico- and thalamostriatal connections innervate the principal neurons of the striatum, the spiny projection neurons (SPNs), which constitute the main cellular input as well as the only output of the striatum. In addition, corticostriatal and thalamostriatal inputs also innervate striatal interneurons. Some of these inputs have been very well studied, for example the thalamic innervation of cholinergic interneurons and the cortical innervation of striatal fast-spiking interneurons, but inputs to most other GABAergic interneurons remain largely unstudied, due in part to the relatively recent identification and characterization of many of these interneurons. In this review, we will discuss and reconcile some older as well as more recent data on the extrinsic excitatory inputs to striatal interneurons. We propose that the traditional feed-forward inhibitory model of the cortical input to the fast-spiking interneuron then inhibiting the SPN, often assumed to be the prototype of the main functional organization of striatal interneurons, is incomplete. We provide evidence that the extrinsic innervation of striatal interneurons is not uniform but shows great cell-type specificity. In addition, we will review data showing that striatal interneurons are themselves interconnected in a highly cell-type-specific manner. These data suggest that the impact of the extrinsic inputs on striatal activity critically depends on synaptic interactions within interneuronal circuitry.

Compartmental function and modulation of the striatum

“…A great deal is known about how interneurons guide circuit function within compartments, or at least in the presumptive matrix (Assous & Tepper, 2019;Banghart, Neufeld, Wong, & Sabatini, 2015;Crittenden et al, 2017), and clues suggesting how local microcircuitry preferentially impacts striosome versus matrix SPN activity are emerging (Banghart et al, 2015;Friedman et al, 2015). But the precise role that interneurons play in functionally linking striosome and matrix circuits is a crucial area for future study (see Amemori et al, 2011).…”

Loss of striatal tyrosine‐hydroxylase interneurons impairs instrumental goal‐directed behavior

“…Approximately 95% of striatal neurons are spiny projection neurons (SPNs), with the remainder consisting of interneurons (Gerfen & Surmeier, ; Graveland & Difiglia, ). Recently, the diversity of known cell types comprising striatal interneurons has expanded, and with the discovery of these new classes of interneurons come new questions regarding their functions (Assous & Tepper, ; Munoz‐Manchado et al., ; Tepper, Tecuapetla, Koos, & Ibanez‐Sandoval, ). Tyrosine‐hydroxylase expressing interneurons (THINs) are a class of interneurons identified based on their unique electrophysiological characteristics and expression of TH (although they are not dopaminergic [Xenias, Ibanez‐Sandoval, Koos, & Tepper, ]).…”

“…THINs are located in dorsal and ventral striatum, in predominately matrix and Mu‐opioid receptor domains in ventral striatum (Unal, Ibanez‐Sandoval, Shah, Abercrombie, & Tepper, ). THINs are also responsive to dopamine and acetylcholine, via activation of D1/D5 and nicotinic receptors, respectively (Assous & Tepper, ; Ibanez‐Sandoval, Xenias, Tepper, & Koos, ).…”

Ablation of striatal somatostatin interneurons affects MSN morphology and electrophysiological properties, and increases cocaine‐induced hyperlocomotion in mice

“…About 95% of neurons composing the striatum are GABAergic medium spiny neurons (MSNs), which receive dense glutamatergic and dopaminergic inputs from the cerebral cortex, thalamus, substantia nigra pars compacta and ventral tegmental area (Bolam, Hanley, Booth, & Bevan, ), respectively. The remaining 5% of the resident neurons of the striatum correspond to non‐spiny interneurons that are known to tightly control MSN activity (Assous & Tepper, ; Kreitzer, ; Zucca, Zucca, Nakano, Aoki, & Wickens, ). Among these, somatostatin/neuropeptide Y/nitric oxide synthase (SST/NPY/NOS)‐expressing interneurons (SSTi), also known as persistent and low‐threshold spiking (PLTS) cells, constitute a well‐identified sub‐category and consist of about 0.7% of the total number of striatal neurons in rodents (Larsson, Lindvall, & Kokaia, ; Tepper et al., ).…”