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Control of interneuron numbers in nascent striatal networks


Brain function requires appropriate numbers of different subtypes of neurons, but how these numbers are established remain poorly understood.

In a new study, out now in PNAS, Varun Sreenivasan and colleagues from the Marin lab,  investigated how the appropriate number of local interneurons is established in an important part of the brain, the striatum. Striatal interneurons comprise two main subtypes: 1) Interneurons expressing the gene Pv release the inhibitory neurotransmitter GABA and control the activity of the principal striatal neurons known as the medium spiny neurons; 2) Interneurons expressing the gene ChAT release the neurotransmitter acetylcholine and are involved in modulating the activity of the medium spiny neurons.

Sreenivasan et al. found that both these populations undergo programmed cell-death during a specific period (P6-P10) of post-natal brain development. Interestingly, the underlying mechanisms that rescue these interneurons from cell-death to establish appropriate numbers were different for these two populations. In the case of the PV interneurons, long-range excitatory inputs from neurons in another region of the brain, the cortex, was crucial for their survival. In the case of the ChAT interneurons, local inputs from the medium spiny neurons within the striatum regulated their survival.

Striatal dysfunction is associated with different neurodevelopmental disorders that affect movement, cognition and behaviour. Alterations in the number of striatal interneurons have been described in patients with schizophrenia and Tourette syndrome. Elucidating whether similar mechanisms operate in humans may shed new light on the neurobiology of neurodevelopmental disorders.

By Varun Sreenivasan