Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus

Abstract

Cholecystokinin (CCK)- and parvalbumin (PV)-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behavior. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV) than they were in corresponding primary areas (V1, S1, M1, and Aud1). The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favor the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labeling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

N-type calcium channels control GABAergic transmission in brain areas related to fear and anxiety

“…CCK + INs were labeled for histochemistry and electrophysiology using an intersectional labeling approach. Our results are similar to previous studies before by our group and others [27,41,45,48,49]. We found that IPSCs recorded on BLA small CCK + INs co-express VIP, but their function is not known [37,51].…”

“…CCK + INs are also abundant in the mPFC, where they are the most common type of interneuron [49]. We next tested if CCK + INs in mPFC rely on N-type calcium channels to release GABA.…”

“…No differences associated with sex were detected in our experiments. To visualize CCK + INs in the BLA and mPFC, we utilized intersectional labeling with Cre and Flpe recombinases under the CCK and Dlx5/6 promoters, respectively [48,49]. We used this approach because CCK is broadly expressed in both PNs and interneurons, whereas Dlx5/6 is restricted to interneurons of the forebrain (Figure 1) [48,50].…”

Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus

“…We focused on parvalbumin positive cells because of their abundance in hippocampus as compared to other interneuron types (Celio, 1986; Tamamaki et al, 2003; Whissell et al, 2015). In addition, parvalbumin positive interneurons phenotypes in adult P50 Bloc1s8 sdy/sdy hippocampus are shared with other interneurons, which we previously scored with diverse GABAergic transcript markers (Larimore et al, 2014).…”

Tissue and cell-type specific expression of a splice variant in the II-III cytoplasmic loop ofCacna1b

“…Mice lacking e18a or De18a-only (Cacna1b tm4.1Dili ) were back crossed in C57BL/6 (Charles River) background for 6-8 generations, for details on how this mouse line was generated see [16]. To label CCK + INs with tdTomato (tdT), we performed intersectional genetic labeling as previously reported [22,23]. We utilized CCK-Cre (Cck tm1.1(cre)Zjh /J, Jax:012706) in C57BL/6 background, Dlx5/6-Flpe (Tg(mI56iflpe)39Fsh/J, Jax: 010815) in FVB/NJ background, and Ai65-D (B6;129S-Gt(ROSA)26Sort m65.1(CAG-tdTomato)Hze /J, Jax: 021875) in C57BL/6;I129 background mice.…”