Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a^EGFPMouse

Abstract

Histological and morphological studies indicate that approximately 5% of striatal neurons are cholinergic or γ-aminobutyric acidergic (GABAergic) interneurons (gINs). However, the number of striatal neurons expressing known interneuron markers is too small to account for the entire interneuron population. We therefore studied the serotonin (5HT) receptor 3a-enhanced green fluorescent protein (5HT3a(EGFP)) mouse, in which we found that a large number of striatal gINs are labeled. Roughly 20% of 5HT3a(EGFP)-positive cells co-express parvalbumin and exhibit fast-spiking (FS) electrophysiological properties. However, the majority of labeled neurons do not overlap with known molecular interneuron markers. Intrinsic electrical properties reveal at least 2 distinct novel subtypes: a late-spiking (LS) neuropeptide-Y (NPY)-negative neurogliaform (NGF) interneuron, and a large heterogeneous population with several features resembling low-threshold-spiking (LTS) interneurons that do not express somatostatin, NPY, or neuronal nitric oxide synthase. Although the 5HT3a(EGFP) NGF and LTS-like interneurons have electrophysiological properties similar to previously described populations, they are pharmacologically distinct. In direct contrast to previously described NPY(+) LTS and NGF cells, LTS-like 5HT3a(EGFP) cells show robust responses to nicotine administration, while the 5HT3a(EGFP) NGF cell type shows little or no response. By constructing a molecular map of the overlap between these novel populations and existing interneuron populations, we are able to reconcile the morphological and molecular estimates of striatal interneuron numbers.

Parvalbumin Interneurons Modulate Striatal Output and Enhance Performance during Associative Learning

“…For example, PV cells in the dorsomedial striatum (Corbit and Janak, 2010) or nucleus accumbens (Day and Carelli, 2007) may have a stronger role in forming stimulus-reward associations than these interneurons in the DLS, which our data showed regulate the expression of conditioned behaviors. Additionally, striatal PV interneurons appear to represent a molecularly, electrophysiologically, and morphologically diverse population (Koos and Tepper, 1999; Munoz-Manchado et al, 2016), and it is unknown whether these subtypes serve different behavioral functions.…”

Local and afferent synaptic pathways in the striatal microcircuitry

“…In the neocortex, the 5HT3a-expressing neurons are prevalent in superficial cortical layers and together with the PV-and SOM-expressing interneurons, could account for almost all GABAergic interneurons. In the same mouse line 5HT3a-expressing interneurons were also characterized in the striatum, revealing a large and diverse population [12]. Similar to TH-expressing interneurons, striatal 5HT3a-EGFP interneurons exhibit distinct electrophysiological subtypes, as well as different co-expression patterns with PV, NOS, TH, and calretinin.…”

Neurogliaform cells in cortical circuits

“…Whether the neocortex harbors a similar Ivy cell population remains an open question. Finally, NPY- negative NGF-cells have been reported in both cortical layer I (termed the elongated NGF cell) 16 and striatum 17 raising the possibility that there exists a third NGF cell type that has not been previously included in any classification schemes or whose origins have been identified through genetic approaches.…”