Parvalbumin interneuron cell-to-network plasticity: mechanisms and therapeutic avenues

Rescuing memory deficits remains a major challenge in treating Alzheimer’s disease (AD) and schizophrenia (SCZ).Parvalbumin interneurons (PVIs) mediate network activities relevant to memory functions. Current research suggests that the ability of PVIs to functionally adapt upon increased network activity underlies the generation of memories. The cell-type-specific interaction of neuronal plasticity on the cellular and network level (PVI cell-to-network plasticity) is a promising target in addressing memory deficits.Two clinically accessible strategies targeting PVI plasticity have emerged for the treatment of memory deficits in AD and SCZ: PVI-specific neuromodulation and high-frequency stimulation in the gamma frequency range (40 Hz).Research into clinically assessing PVI cell-to-network plasticity in humans will be essential to transfer current findings into clinical practice. Alzheimer’s disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory deficits in AD and SCZ, and we explore two therapeutic avenues: the targeting of PVI-specific neuromodulation, including by neuropeptides, and the recruitment of network synchrony in the gamma frequency range (40 Hz) by external stimulation. We finally propose that these approaches be merged under consideration of recent insights into human brain physiology. Alzheimer’s disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory d