Rethinking parvalbumin: From passive marker to active modulator of hippocampal circuits

重新认识小白蛋白:从被动标记物到海马回路的主动调节剂

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Abstract

Parvalbumin (PV)-expressing interneurons are critical regulators of neural circuit dynamics, and for decades, the PV protein has served as their definitive molecular marker. This review confronts a central, yet underappreciated, paradox: the incongruity of a kinetically slow Ca²⁺ buffer (PV) being the defining feature of the brain's fastest-spiking neurons. We synthesize evidence from molecular biophysics, genetics, in vivo circuit analysis, and disease modeling to dissect the dual role of PV as both a cellular marker and an active functional regulator. We argue that PV's slow kinetics are not a coincidence but a crucial adaptation that shapes short-term synaptic plasticity, protects against metabolic stress during high-frequency firing, and allows the circuit to shift between states of plasticity and stability. This reframing resolves the paradox by demonstrating how a "slow" molecule is essential for "fast" neuronal function. Furthermore, we highlight that dysfunction of the PV system is a convergent hub of pathology in numerous neurological and psychiatric disorders, including schizophrenia, epilepsy, and Alzheimer's disease. By moving beyond its identity as a passive marker, we establish PV as an active modulator of neural computation and a potential therapeutic target for restoring network function in disease.

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