Transcriptomics survey of inhibitory and excitatory neurons
Neuronal diversity is a key property of the brain. This diversity helps to create different brain activity patterns and behavior. Cell type classification schemes have provided us with a detailed understanding of the distinct types that constitute this diversity and their contribution to brain function.
In recent years, the use of single-cell RNAseq greatly extended this existing framework, especially expanding our understanding of the molecular features of different neuronal types. Recent insights have highlighted that synaptic cell surface receptors and adhesion molecules are particularly good predictors of cell type identity.
Because cell adhesion molecules play critical roles in neural circuit assembly and are frequently associated with neurodevelopmental and psychiatric disorders, they could potentially also predict circuit connectivity and function. Our work focuses on cortical, hippocampal and midbrain neurons with the aim of making a leap torwards this direction.
Neuronal rewiring events in the mature brain
Since the original description of quantal transmission, a defining feature of all synapses, it has become clear that trans-synaptic molecular signaling between the pre- and the post-synapse is key to proper brain function.
Trans-synaptic signaling is enabled by synaptic cell surface receptors and adhesion molecules, and is important for axon outgrowth, target-cell recognition, synapse formation, and maintaining transmission in mature synapses. Unraveling these mechanisms at a genetic and molecular level is of key importance.
Ultimately, this knowledge will lead to an understanding of how genetic mutations in these synaptic molecules lead to neurodevelopmental and neuropsychiatric disorders in humans. It will also lead to a better understanding of how target-specific rewiring—the ability of which is lost during development—can be restored in mature neurons. Solving these problems is a prerequisite for brain repair after injury and could aid development of novel therapies for neurological disorders.