Localization of Calcium-binding Proteins in Physiologically and Morphologically Characterized Interneurons of Monkey Dorsolateral Prefrontal Cortex

Abstract

In the primate neocortex, little is known about the possible associations between functional subclasses of GABA neurons, their morphological properties and calcium-binding protein (CaBP) content. We used whole-cell current clamp recordings, combined with intracellular labeling and fluorescence immunohistochemistry, to determine these relationships for interneurons in layers 2-3 of monkey prefrontal cortex (PFC). Eighty-one interneurons were included in the analysis. Thirty-eight of these cells showed immunoreactivity for one of the three CaBPs tested. Co-localization of more than one CaBP was not observed in any of the interneurons examined. Interneurons with different CaBPs formed distinct populations with specific physiological membrane properties and morphological features. Parvalbumin (PV)-positive cells had the physiological properties characteristic of fast-spiking interneurons (FS) and the morphology of basket or chandelier neurons. Most calretinin (CR)-containing cells had the physiological properties ascribed to non-fast-spiking cells (non-FS) and a vertically oriented axonal morphology, similar to that of double bouquet cells. Calbindin (CB)-positive interneurons also had non-FS properties and included cells with double bouquet morphology or with a characteristic dense web of axonal collaterals in layer 1. Classification of the interneurons based on cluster analysis of multiple electrophysiological properties suggested the existence of at least two distinct groups of interneurons. The first group contained mainly PV-positive FS cells and the second group consisted predominantly of CR- and CB-positive non-FS interneurons. These findings may help to illuminate the functional roles of different groups of interneurons in primate PFC circuitry.

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

“…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.…”

“…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). In contrast, CB-IR interneurons have a double bouquet morphology, form characteristic dense axonal collaterals in layer I, make synapses on the dendrites and dendritic spines of pyramidal neurons, and have physiological features consistent with nonfast spiking interneurons (Cauli et al, 1997;DeFelipe, 1997;Gabbott et al, 1997;Kubota, 1993, 1997;Lund and Lewis, 1993;Zaitsev et al, 2005).…”

“…PV-IR neurons have physiological properties characteristic of fast-spiking interneurons Kubota, 1993, 1997;Zaitsev et al, 2005). In contrast, CB-IR interneurons have a double bouquet morphology, form characteristic dense axonal collaterals in layer I, make synapses on the dendrites and dendritic spines of pyramidal neurons, and have physiological features consistent with nonfast spiking interneurons (Cauli et al, 1997;DeFelipe, 1997;Gabbott et al, 1997;Kubota, 1993, 1997;Lund and Lewis, 1993;Zaitsev et al, 2005). In addition, CB and PV cortical neurons differ by specific serotoninergic and dopaminergic innervation (Freund et al, 1990;Hornung, 2003;Hornung and Celio, 1992;Sesack et al, 1995).…”

“…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).…”

Subpopulations of neurons expressing parvalbumin in the human amygdala

“…Unlike PVB, CB has been shown to interact with protein and/or subcellular structures, suggesting a possible role in signal transduction or activity-dependent changes of its intracellular mobility . These differences are also reflected in the physiological properties of primate and rodent CB-IR neurons, described as "low-threshold spike cells" (Kawaguchi and Kubota, 1993) (Zaitsev et al, 2005), indicating an electrophysiological profile fundamentally different from that displayed by the "fast-spiking" PVB-IR neurons.In light of these differences, it is interesting to note that CB is coexpressed in large populations of PVB-IR neurons within the rodent neocortex, amygdala, and cerebellum (Celio, 1990;Kubota and Jones, 1993;Kubota et al, 1994;McDonald and Mascagni, 2001). Growing evidence indicates that, when coexpressed, CB and PVB may interact synergistically .…”