Heterogeneity and Diversity of Striatal GABAergic Interneurons: Update 2018

Abstract

Our original review, “Heterogeneity and Diversity of Striatal GABAergic Interneurons,” to which this is an invited update, was published in December, 2010 in Frontiers is Neuroanatomy. In that article, we reviewed several decades’ worth of anatomical and electrophysiological data on striatal parvalbumin (PV)-, neuropeptide Y (NPY)- and calretinin(CR)-expressing GABAergic interneurons from many laboratories including our own. In addition, we reported on a recently discovered novel tyrosine hydroxylase (TH) expressing GABAergic interneuron class first revealed in transgenic TH EGFP reporter mouse line. In this review, we report on further advances in the understanding of the functional properties of previously reported striatal GABAergic interneurons and their synaptic connections. With the application of new transgenic fluorescent reporter and Cre-driver/reporter lines, plus optogenetic, chemogenetic and viral transduction methods, several additional subtypes of novel striatal GABAergic interneurons have been discovered, as well as the synaptic networks in which they are embedded. These findings make it clear that previous hypotheses in which striatal GABAergic interneurons modulate and/or control the firing of spiny neurons principally by simple feedforward and/or feedback inhibition are at best incomplete. A more accurate picture is one in which there are highly selective and specific afferent inputs, synaptic connections between different interneuron subtypes and spiny neurons and among different GABAergic interneurons that result in the formation of functional networks and ensembles of spiny neurons.

Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency

“…GABAergic interneurons in the striatum play important roles in regulating network function and behaviors (Tepper et al, ). GABAergic PV‐positive fast spiking inhibitory interneurons constitute ~3% of the neuron population in rodent striatum, control the bursting of MSNs, and modulate the circuit output (O'Hare et al, ; Owen et al, ).…”

“…GABAergic interneurons in the striatum play important roles in regulating network function and behaviors (Tepper et al, 2018).…”

“…In addition to the MSNs, there are GABAergic interneurons in the striatum that play important roles in regulating network function (Tepper et al, 2018). For example, parvalbumin (PV)-expressing fast-spiking interneurons control the bursting of MSNs and modulate the circuit output (O'Hare et al, 2017;Owen, Berke, & Kreitzer, 2018).…”

Translating striatal activity from brain slice to whole animal neurophysiology: A guide for neuroscience research integrating diverse levels of analysis

“…The initial impetus for the attribution of functional heterogeneity came from the realization that the anatomy of these structures was not so simply homogeneous (Berridge, 2019;Haber, 2016;Kemp & Powell, 1970;Mensah, 1977;Tepper et al, 2018). Modern neuroscience has been increasingly adding diverse functional centers into the BG system, making the system comprised of many, possibly separable subfunctions.…”

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

“…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, 2019;Kreitzer, 2009;Zucca, Zucca, Nakano, Aoki, & Wickens, 2018). 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, 2001;Tepper et al, 2018). It is worth noting that an additional sub-population of NPY-containing striatal interneurons, the NPY-neurogliaform neurons, has been recently identified (Ibanez-Sandoval et al, 2011).…”