Using knockout mouse models to investigate synaptic pruning

Summary The Neuron Development and Plasticity group, led by Jenny Gunnersen, has the broad research goal of understanding how neurons become connected into functional circuits. We investigate the formation of dendritic branches and synapses, the connections between neurons, in development and in disease models.

Project Details

The Neuron Development and Plasticity group, led by Jenny Gunnersen, has the broad research goal of understanding how neurons become connected into functional circuits. We investigate the formation of dendritic branches and synapses, the connections between neurons, in development and in disease models. Changes in the number and strength of synaptic connections (plasticity) are vital for the development of effective neuronal circuitry and for learning and memory in the healthy brain.

On the other hand, abnormal synapse numbers and activity are defining features of neurological disorders. Learning more about dendrite and synapse development and function in the healthy brain will help us decipher the aberrant molecular pathways responsible for cognitive disorders such as mental retardation, epilepsy, schizophrenia and dementia.

Microglia are sentinels of the brain circuitry involved in "pruning" of weak or inactive synapses during development and monitoring and refining synaptic connectivity in the adult brain. A mechanism for "tagging" unnecessary synapses for removal has been described, however whether a complementary mechanism exists to protect active synapses from being pruned is a major unanswered question. The effect of gene knockout on putative pruning regulators will be determined.