Neuronal activity operates within a tightly controlled range for the optimal functioning of neural circuits. When synaptic connectivity and network activity are modified, such as when we are learning, compensatory mechanisms are needed to support stability. While we know a fair amount about plasticity in excitatory pyramidal cells, we understand little about how inhibitory interneurons adapt to sustained changes in their activity.
Exciting new work published in Nature by Martijn Selten and colleagues in the Marín lab has revealed a critical mechanism through which parvalbumin-expressing (PV+) interneurons regulate their own inhibition to respond to changes in their activity. In this study, Selten and colleagues found that when PV+ interneuron activity is increased, they promote receiving more inhibitory inputs from other PV+ interneurons, effectively rebalancing their activity.
The team identified neuropeptide-encoding genes Vgf and Scg2 as key regulators of this plasticity through their analyses of gene expression changes occurring in these interneurons upon activation. Selten and colleagues performed functional experiments that confirmed Vgf is essential for increasing inhibitory synapses specifically from PV+ interneurons following heightened activity. These mechanisms were further observed in a fear-conditioning model, where PV+ interneurons activated during memory formation upregulated Vgf and strengthened their inhibitory connections, indicating a role for this process in learning and memory.
These findings illustrate a previously unknown form of interneuron plasticity and suggest that neuropeptide signalling indeed plays a crucial role in maintaining neural circuit stability. A thorough understanding of these processes and mechanisms is critical for our understanding, and improved treatment of, neurodevelopmental and neuropsychiatric disorders, where inhibitory circuit dysfunction is implicated.