Fast-spiking parvalbumin-positive interneurons in brain physiology and Alzheimer’s disease

Fast-spiking parvalbumin (PV) interneurons are inhibitory interneurons with unique morphological and functional properties that allow them to precisely control local circuitry, brain networks and memory processing. Since the discovery in 1987 that PV is expressed in a subset of fast-spiking GABAergic inhibitory neurons, our knowledge of the complex molecular and physiological properties of these cells has been expanding. In this review, we highlight the specific properties of PV neurons that allow them to fire at high frequency and with high reliability, enabling them to control network oscillations and shape the encoding, consolidation and retrieval of memories. We next discuss multiple studies reporting PV neuron impairment as a critical step in neuronal network dysfunction and cognitive decline in mouse models of Alzheimer’s disease (AD). Finally, we propose potential mechanisms underlying PV neuron dysfunction in AD and we argue that early changes in PV neuron activity could be a causal step in AD-associated network and memory impairment and a significant contributor to disease pathogenesis.