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From neuronal circuits and microglial…

The brain is assembled from thousands of cell types, which are functionally organized in neuronal circuits. These circuits collect, encode, and process environmental information, resulting in a behavior outcome. Classical studies have provided important insights into the necessity of correct neuronal wiring and circuit structure maintenance. Malformation of neuronal circuits always results in a disease phenotype at any level:

  • during neurodevelopment, when the intended circuit is not build up correctly; or
  • during neurodegeneration, when circuit elements start to fail.

In our laboratory, we are addressing circuit malfunction from a new perspective namely approaching it from the point of the immune system:

Microglia are the CNS-resident macrophages, mostly sitting in the synaptic connectivity layers, and continuously sensing their neuronal environment. They switch between functional states that either promote or counteract removal of circuit elements. But how microglia decide when to alter circuit elements without inducing circuit malfunction is not known?

Activated microglia are a feature of CNS pathologies such as glaucoma and Alzheimer’s disease. Thus, it is important to study the contribution of these cells and to develop strategies for manipulating them in a beneficial manner.