Local circuit neurons immunoreactive for calretinin, calbindin D‐28k or parvalbumin in monkey prefronatal cortex: Distribution and morphology

Abstract

In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states.

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

“…Primate studies reveal that GABAergic inhibitory nonpyramidal neurons can be divided into nonoverlapping subpopulations based on the calcium binding protein, CB, PV or calretinin, they express (Conde et al, 1994;Lund and Lewis, 1993). These three subgroups together account for virtually all GABAergic neurons.…”

“…Note that the density of CB-IR neurons was significantly inversely correlated with age in the MDD group but not in the control group. GABAergic neurons in depression G Rajkowska et al prefrontal neurons belong to two distinct subpopulations of GABA interneurons (Conde et al, 1994;Zaitsev et al, 2005). These cells differ by morphology, type of contacts with pyramidal neurons, pattern of firing, and monoaminergic innervation.…”

“…These cells differ by morphology, type of contacts with pyramidal neurons, pattern of firing, and monoaminergic innervation. PV-IR interneurons correspond to basket or chandelier cells, make contacts on somata and axonal initial segments of pyramidal neurons and regulate cortical output activity (Baimbridge et al, 1992;Cauli et al, 1997;Conde et al, 1994;Cruz et al, 2003;DeFelipe, 1989DeFelipe, , 1997Gabbott et al, 1997;Lewis and Lund, 1990;Lund and Lewis, 1993;Somogyi et al, 1998). PV-IR neurons have physiological properties characteristic of fast-spiking interneurons Kubota, 1993, 1997;Zaitsev et al, 2005).…”

“…Owing to differences in the laminar distribution of CB-IR as compared to PV-IR interneurons described in monkey and human prefrontal cortex (Conde et al, 1994;Miguel-Hidalgo and Rajkowska, 1999), CB-IR neurons were analyzed in superficial layer II and upper part of layer III, the sites of greatest prominence. PV-IR neurons were counted in layers III-VI where they are present in the highest density.…”

“…Other studies of post-mortem human and primate cerebral cortex have identified three distinct subpopulations of nonpyramidal GABAergic neurons that can be identified with antibodies specific to calcium binding proteins: calbindin-D28k (CB), parvalbumin (PV), and calretinin (Beasley et al, 2002;Conde et al, 1994;Cotter et al, 2002a;DeFelipe, 1997;Uylings et al, 2002;Zaitsev et al, 2005). Only two human post-mortem studies have investigated these neuronal subpopulations in depression (Beasley et al, 2002;Cotter et al, 2002a).…”