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Parvalbumin-Containing Chandelier and Basket Cell Axon Terminals have Distinctive Modes of Maturation in Monkey Prefrontal Cortex

Fish KN, Hoftman G, Sheikh W, Kitchens M, and Lewis DA

Schizophrenia is a neurodevelopmental disorder that afflicts approximately 1.0% of the world?s population. While positive symptoms (i.e. psychotic symptoms) are most commonly associated with the illness, cognitive deficits are the core dysfunction. Cognitive functions can be linked to the coordinated activity of ensembles of excitatory and inhibitory neurons in the prefrontal cortex (PFC).

A subset of inhibitory neurons expresses the calcium-binding protein parvalbumin (PV), which include chandelier cells (PVChCs) and basket cells (PVBCs).  Axons from multiple PVChCs converge to form a vertical array of synapses known as a cartridge (arrows in the figure above) exclusively on the axon initial segment (AIS) of excitatory pyramidal neurons. In monkey PFC, the density of PVChC axon cartridges detectable by PV immunoreactivity peaks prior to the onset of puberty before declining markedly to adult levels, whereas the density of PV-immunoreactive (IR) puncta (presumed PVBC terminals) increases during adolescence. To assess whether these changes in density are due to alterations in synapse number or cell-type specific differences in the maturation of PV protein levels, Drs. Fish, Hoftman and colleagues performed multi-label confocal microscopy to quantify the number of PVChC and PVBC appositions per pyramidal neuron in the PFC of 3 month old and adult monkeys.   

The mean number of PVChC appositions per pyramidal neuron AIS was a significant 32% lower in adult compared to 3 month old monkeys, whereas the density of PVBC connections per pyramidal neuron did not differ between age groups. In contrast, relative levels of PV protein were two-fold higher in PVBC appositions in adult animals, whereas PV levels in PVChC appositions did not differ between age groups. These findings reveal cell type-specific differences in the maturation of PV-containing GABAergic axon terminals in monkey PFC. These differences may provide insight into the nature or timing of the reported alterations in these types of axon terminals in schizophrenia.

Contributors:
Kenneth N. Fish, PhD, Gil Hoftman, PhD, Wasiq Sheikh, Michael Kitchens, and David A. Lewis, MD (Department of Psychiatry and Center for Neuroscience, University of Pittsburgh)

The results of this investigation were published in the Journal of Neuroscience. Click here for a link to the abstract.