Three distinct families of GABAergic neurons in rat visual cortex

Abstract

In the cortex inhibition is mediated predominantly by GABAergic interneurons. Although all of these neurons use the same neurotransmitter, studies in the rat frontal cortex have shown that they are molecularly and physiologically diverse. It is not known whether similar subgroups of GABAergic neurons exist in primary visual cortex and how these different inhibitory neurons are inserted into specific cortical circuits. We have used immunostaining with antibodies against gamma aminobutyric acid (GABA), parvalbumin (PV), calretinin (CR), somatostatin (SOM), calbindin (CB) and nitric oxide synthase (NOS) to probe for colocalization of known markers of GABAergic interneurons. The results show that the majority of PV (100%), SOM (89.8%) and CR (93.9%) staining neurons are GABA positive. PV immunoreactive neurons constitute a distinct group that show no overlap with CR, SOM and NOS expressing cells and only a minor overlap (5.3%) with CB. PV immunoreactive cells account for 50.8% of GABAergic neurons. A second group of SOM expressing neurons accounts for 16.9% of GABAergic cells. None of these cells colocalize PV or CR, but 1.7% of SOM neurons stain for NOS and 86.3% show CB immunoreactivity. The third distinct group of CR expressing cells accounts for 17.0% of GABAergic neurons. All of these are PV, CB, SOM and NOS negative. CB expressing neurons represent a heterogeneous group that includes GABAergic and non-GABAergic cells. Our findings indicate that GABAergic neurons in rat area 17 are organized in at least three separate families that can be identified by the expression of PV, CR and SOM. These cells account for 84.9% of GABAergic neurons. These results extend previous observations in rat frontal agranular cortex and suggest that in visual cortex the inhibitory network is composed of similar cell types.

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

“…To classify cortical TH-IR neurons into one or more of the three nonoverlapping subsets of interneurons as well as to provide indirect evidence for the embryonic origin of TH-IR cells, we examined the colocalization of TH with parvalbumin, somatostatin, or calretinin (Kubota et al, 1994;Gonchar and Burkhalter, 1997;Xu et al, 2004), the expression of which is unique to their site of origin (Wichterle et al, 2001;Nery et al, 2002;Flames and Marin, 2005;Wonders and Anderson, 2006). Parvalbumin-, somatostatin-and calretinin-IR cell profiles were observed in the cortex (Fig.…”

“…The current report is the first to classify cortical TH-IR neurons into one of the three nonoverlapping subsets of cortical interneurons that are defined by their production of parvalbumin, somatostatin, or calretinin (Kubota et al, 1994;Gonchar and Burkhalter, 1997;Xu et al, 2004). The finding that approximately one-third to one-half of cortical TH-IR cell profiles were colocalized with calretinin, whereas very few TH cell profiles were colabeled with parvalbumin or somatostatin, suggests that many of these TH-IR neurons belong to the calretinin-containing subset.…”

“…In addition to gamma aminobutyric acid (GABA), the calcium-binding proteins parvalbumin and calretinin and the peptide somatostatin are present in three non-overlapping subsets of inhibitory interneurons (Kubota et al, 1994;Gonchar and Burkhalter, 1997;Xu et al, 2004). Interneurons that express parvalbumin and somatostatin migrate from the MGE, whereas those producing calretinin arise in the CGE (Wichterle et al, 2001;Nery et al, 2002;Xu et al, 2004).…”

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

“…Thus, supposing that Arx-positive neurons in the cortex were probably GABAergic neurons, we performed colabeling stainings with Arx and markers of mature and functional interneurons. For instance, calbindin and calretinin are widely used markers of cortical GABAergic neurons, although they do not stain the overall population, but each of them labeling a specific fraction (Gonchar and Burkhalter, 1997). Double staining Arx/calbindin and Arx/calretinin were performed in adult brain coronal sections.…”

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

“…PV, CCK and SST are expressed in separate classes of cortical interneurons. [64][65][66][67][68] In interneurons SST, NPY and TAC1 are co-expressed to a great extent and SST/NPY expression can be induced by a BDNF/ TrkB-dependent mechanism. [69][70][71] While we observed a strong downregulation in the SST-NPY-TAC1 transcripts in both adult and embryonic BDNF-ablated mice, we found the expression of other GABA colocalizing neuropeptides and GABA-production enzymes unchanged.…”