GABA-Synthesizing Enzymes in Calbindin and Calretinin Neurons in Monkey Prefrontal Cortex

Abstract

Non-overlapping groups of cortical γ-aminobutyric acid-releasing (GABAergic) neurons are identifiable by the presence of calbindin (CB), calretinin (CR), or parvalbumin (PV). Boutons from PV neuron subtypes are also distinguishable by differences in protein levels of the GABA-synthesizing enzymes GAD65 and GAD67. Multilabel fluorescence microscopy was used to determine if this diversity extends to boutons of CB and CR neurons in monkey prefrontal cortex. CB and CR neurons gave rise to 3 subpopulations of GAD-containing boutons: GAD65+, GAD67+, and GAD65/GAD67+. Somatostatin and vasoactive intestinal peptide-expressing neurons, subtypes of CB and CR neurons, respectively, also gave rise to these distinct bouton subpopulations. At the transcript level, CB and CR neurons contained mRNA encoding GAD67-only or both GADs. Thus, the distinct subpopulations of CB/GAD+ and CR/GAD+ boutons arise from 2 unique subtypes of CB and CR neurons. The different CB and CR GAD-expressing neurons targeted the same projection neurons and neuronal structures immunoreactive for PV, CR, or CB. These findings suggest that GABA synthesis from CB/GAD67+ and CR/GAD67+ neurons would presumably be more vulnerable to disease-associated deficits in GAD67 expression, such as in schizophrenia, than neurons that also contain GAD65.

Keywords: GAD65; GAD67; glutamic acid decarboxylase; somatostatin; vasoactive intestinal peptide.