Parvalbumin and parvalbumin chandelier interneurons in autism and other psychiatric disorders

Abstract

Parvalbumin (PV) is a calcium binding protein expressed by inhibitory fast-spiking interneurons in the cerebral cortex. By generating a fast stream of action potentials, PV+ interneurons provide a quick and stable inhibitory input to pyramidal neurons and contribute to the generation of gamma oscillations in the cortex. Their fast-firing rates, while advantageous for regulating cortical signaling, also leave them vulnerable to metabolic stress. Chandelier (Ch) cells are a type of PV+ interneuron that modulate the output of pyramidal neurons and synchronize spikes within neuron populations by directly innervating the pyramidal axon initial segment. Changes in the morphology and/or function of PV+ interneurons, mostly of Ch cells, are linked to neurological disorders. In ASD, the number of PV+ Ch cells is decreased across several cortical areas. Changes in the morphology and/or function of PV+ interneurons have also been linked to schizophrenia, epilepsy, and bipolar disorder. Herein, we review the role of PV and PV+ Ch cell alterations in ASD and other psychiatric disorders.

Keywords: autism; chandelier cell; interneuron; parvalbumin; schizophrenia.

Figure 1

Chandelier cell connectivity and immunostaining. (A) Chandelier cells (blue) have a unique and structurally complex morphology characterized by vertically oriented axon terminal cartridges (red and green), that are perpendicular to the pial surface. Ch cells synapse onto the AIS of pyramidal neurons (orange) and can innervate up to 250 pyramidal cells at once, allowing for fine inhibitory control. (B) Ch cell in primary somatosensory cortex stained with an anti-PV antibody that labels the soma and proximal processes (BA3). Triple enzymatic stain of CR (Blue), CB (Brown) and PV (Pink) labeled interneurons reveals loss of PV+ interneurons in BA3 of both control (C) and ASD cortex (D). Scale Bars = 20 μm.