Molecular mechanisms underlying the formation and plasticity of inhibitory synapses

Neuronal circuits in our brain have an enormous capacity to adapt during development, when learning, or in response to injury or disease. In a healthy brain, changes in excitatory and inhibitory synapses are coordinated to preserve neuronal and network function. Recent experimental and computational studies have demonstrated that particularly inhibitory synapses, even though they are only ~15% of all synapses in the brain, are very important in controlling synaptic plasticity and shaping information processing in the brain. Inhibitory synapses also represent a vulnerability of the brain. Impaired inhibitory signaling is at the basis of many neurodevelopmental and other brain disorders, including autism and early stages of Alzheimer’s disease.

In the Wierengalab we are interested in the role of inhibitory synapses at the molecular, cellular and network level. We study the molecular mechanisms underlying the formation an plasticity of inhibitory synapses using a combination of two-photon microscopy, electrophysiology and molecular approaches in brain slices. Our live imaging studies show that inhibitory synapses are incredibly dynamic. They can be formed or eliminated rapidly depending on local demand. We already unraveled some of the molecular signals that govern the formation of inhibitory synapses and identified an unexpected role for endocannabinoids in local coordination of excitatory and inhibitory synapses within dendrites. Ongoing studies examine changes in inhibitory synapses when normal development is disturbed and in early stages of Alzheimer’s disease.

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• ORCID iD: 0000-0001-9073-4099

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Curriculum Vitae

Donders Centre for Neuroscience