Cellular biology of synapses

The lab is focused on understanding basic mechanisms that control the connections (synapses) that link neurons with each other within the brain. Because synaptic dysfunction is one of the early events underlying disorders such as Alzheimer´s, Parkinson´s or schizophrenia, our research might shed light on the molecular causes of brain disease.

Alterations in excitatory neurotransmission are major factors in the development of neuropsychiatric and neurological diseases. Work in our laboratory is geared towards identifying cellular and molecular links between glutamate receptor function and brain development and pathology. Our current research combines state-of-the-art molecular/cell biological, biochemical and quantitative imaging techniques in vitro (cell lines and primary neuronal culture) and in vivo (transgenic mice) to (1) define cell biological pathways that control synaptic transmission and plasticity at glutamatergic synapses, (2) test how key molecular elements of these pathways might be disrupted in diseases of the Central Nervous System, and (3) assess their therapeutic value.

At the molecular and cell biological level, we are investigating the trafficking and regulation of a specific subtype of glutamate receptors, the NMDA receptor, which plays a key role in synaptic plasticity, neuronal death, and functional disorders of the nervous system. We are particularly interested in understanding the mechanisms that maintain or change the subunit composition of NMDA receptors present at the synapse, and how these processes influence synapse maintenance or modification and ultimately shape synaptic connectivity. At the whole animal level, we are using genetic tools to recapitulate defects in receptor trafficking in vivo in order to generate novel mouse models of neural disease.

Ongoing projects in the lab include:

1. Molecular/cell biological mechanisms of NMDA receptor trafficking.
2. Effects of aberrant protein aggregation on NMDA receptor endocytic trafficking and synapse structure.
3. Role of the inhibitory NMDA receptor subunit NR3A in hippocampal plasticity,synapse remodeling and memory storage.
4. Trafficking of the ADAM10 secretase to the synapse and its role in Alzheimer´s disease.