9/10 In sum, our findings reveal a postnatal molecular switch that drives the activity-dependent maturation of parvalbumin interneurons, a critical population for cortical function. Funded by the @wellcometrust.bsky.social

8/10 Importantly, this mechanism also allows PV interneurons to regulate their mitochondrial content and function, which may also contribute to their maturation

7/10 PGC-1alpha cooperates with ERR-gamma to directly regulate the transcription of many PV-enriched genes. Incidentally, it also seems involved in repressing genes that are typically enriched in other cells, like SST interneurons

6/10 How is this achieved? We discovered that PGC-1alpha regulates the expression of most genes that are typically enriched in mature PV interneurons

5/10 What are the mechanisms regulating the protracted maturation of cortical interneurons? We found that this process requires neuronal activity and is mediated by the transcriptional modulator PGC-1alpha

4/10 Interestingly, while PV interneurons are generated in the embryo, they are late bloomers: in humans, for example, it takes more than two years for PV interneurons to acquire their mature properties

3/10 Several unique properties distinguish PV interneurons: They exert a very tight control over the output of pyramidal cells; are fast-spiking, meaning they can fire action potentials at very high frequencies; are covered by perineuronal nets, and have many mitochondria

2/10 PV interneurons are a type of inhibitory neuron in the cortex, characterized by their expression of the calcium-binding protein parvalbumin. These neurons play a crucial role in regulating neuronal activity and are involved in #memory, sensory processing, and motor control

8/10 Importantly, this mechanism also regulates the connectivity of PV interneurons during learning, for example, in a fear-conditioning paradigm

7/10 For PV interneurons, Vgf is the critical gene modulating the plasticity of inhibitory inputs received from other PV interneurons

5/10 How is this achieved? We found that PV interneurons induce the expression of two genes encoding multiple neuropeptides, Scg2 and Vgf, in response to increased activity

4/10 Using experimental manipulations, we found that PV interneurons scale the inhibition they receive to maintain stability. When the activity of a PV interneuron increases, it “requests” more inhibitory inputs from other PV+ interneurons, effectively rebalancing its activity

3/10 Neuronal activity operates within a tightly controlled range for the optimal functioning of #brain circuits. When synaptic connectivity and network activity are modified, such as when we are learning, compensatory mechanisms are needed to maintain stability

2/10 The cortex contains two main classes of neurons: excitatory “go” pyramidal cells and inhibitory “no-go” #interneurons

1/10 Our latest research, led by @martijnselten.bsky.social, identifies a mechanism through which Parvalbumin (PV) interneurons regulate their activity in the #cortex. This is the story @nature.com
www.nature.com/articles/s41... ⬇︎ 🧵 @devneuro.bsky.social @kingsioppn.bsky.social @erc.europa.eu