Connectivity of GABAergic Calretinin-immunoreactive Neurons in Rat Primary Visual Cortex

Abstract

In rat visual cortex neurons that are immunoreactive for the calcium-binding protein calretinin (CR+) constitute a distinct family which accounts for 17% of gamma-aminobutyric acid (GABA)-expressing cells. It is not clear, however, (i) whether CR is expressed exclusively in GABAergic neurons and (ii) how CR+ neurons are incorporated into neuronal circuits of rat visual cortex. To address these questions we studied synaptic relationships of CR+ neurons with GABA+ and GABA- elements in the neuropil of rat primary visual cortex (area 17). All CR+ neurons are nonpyramidal cells with smooth or sparsely spiny and often beaded dendrites. Of all CR+ neurons, 56% are located in layers 1 and 2/3. In layer 2/3, most CR+ neurons are bipolar-shaped and have vertically oriented dendrites. Many ascending dendritic branches reach layer 1 where they run parallel to pial surface. CR+ axons are thin, highly branched near the cell body and often send descending collaterals to layers 5 and 6. Double immunofluorescence labeling revealed GABA in 94% of CR+ cell bodies in layer 2/3. Electron microscopic analysis shows that all CR+ axon terminals contain elongated vesicles and form symmetric synapses. Postembedding staining shows that 98% of CR+ terminals are GABA+. GABA-immunoreactivity is also present in somata and thick dendrites of CR+ neurons but many thin dendrites are GABA-. CR+ somata, dendrites and axon terminals are enriched in mitochondria. Somata and thick CR+ dendrites are densely innervated. At least 68% of the targets of CR+ terminals in layer 2/3 are GABA+ and > or = 50% of these are other CR+ neurons. The remainder (32%) of targets of CR+ terminals are thin dendrites of GABA- cells. In contrast, in layers 5 and 6, 60% of CR+ terminals form synapses with GABA- somatic profiles. The preferential interactions of layer 2/3 CR+ neurons with GABAergic neurons, and with CR+ neurons in particular, suggests that these cells play a role in the inhibition of inhibitory neurons of the same layer. Through these interactions CR+ cells may reduce inhibition of pyramidal cells in layers 2/3, 5 and 6 and thus disinhibit a column of neurons.

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

“…By P20, the age of peak TH immunoreactivity, the number and distribution of calretinin-IR cells are similar to those in the adult cortex. Most of the calretinin-IR neurons in layer II/III are bipolar (Gonchar and Burkhalter, 1999), similar to the morphology of TH-IR neurons. Interestingly, the majority of the calretinin-IR neurons in this layer make synaptic connections with other GABAergic interneurons (Gonchar and Burkhalter, 1999).…”

“…Interestingly, the majority of the calretinin-IR neurons in this layer make synaptic connections with other GABAergic interneurons (Gonchar and Burkhalter, 1999). One possible function of the TH-and calretinin-copositive interneurons may be to inhibit other inhibitory neurons, thereby disinhibiting pyramidal cells (Gonchar and Burkhalter, 1999).…”

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

“…Functionally, MCR cells seem to be involved in the maintenance of rhythmic activity (theta frequency oscillations), and BCR cells act as ''disinhibitory'' cells relieving layer 2/3 pyramidal cells from inhibition (Caputi et al 2009). BCR cells in the neocortex are interneuron-selective (IS) cells and seem to target specifically other interneurons (Gonchar and Burkhalter 1999).…”

Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex

“…In contrast, non-FS inhibitory interneurons in layer II/III of the cortex predominantly target other inhibitory interneurons in the same layer (Meskenaite, 1997;Gonchar and Burkhalter, 1999) and they may play a role in blockade of inhibitory circuits. In particular, it is suggested that PV-positive, FS basket cell control synchronized outputs of cortical principal cells because of the specific innervation pattern on pyramidal cell bodies (Cobb et al, 1995;Kawaguchi and Kubota, 1997) or the interconnectivity between those GABAergic neurons through electrical and chemical synapses (Galarreta and Hestrin, 2002).…”