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GABA synthesizing enzymes in calbindin and calretinin neurons in monkey prefrontal cortex
Rocco B, Sweet RA, Lewis DA and Fish K
Cerebral Cortex, Published Online

Non-overlapping groups of cortical GABAergic neurons are identifiable by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV).  Previous findings by investigators in Dr. Ken Fish’s laboratory in the Department of Psychiatry at the University of Pittsburgh have shown that boutons (presynaptic axon terminals) from PV neuron subtypes are also distinguishable by differences in protein levels of the GABA synthesizing enzymes GAD65 and GAD67. 

Brad Rocco, a graduate student in the Fish laboratory, and researchers in the Translational Neuroscience Program, used multi-label fluorescence microscopy to determine if this diversity extends to boutons of CB and CR neurons in monkey prefrontal cortex. 

The investigators found that CB and CR neurons gave rise to three 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 two 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 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.

Contributors:
Brad Rocco, BS, Robert A. Sweet, MD, David A. Lewis, MD and Kenneth Fish, PhD (Department of Psychiatry, University of Pittsburgh)

This article appears in the journal Cerebral Cortex.  Click here to view the abstract.