What We Do
Project 1: The Mighty Calyx
We study the mechanisms that permit rapid and sustained synaptic transmission in the mouse brain, predominantly using the calyx of Held as a model synapse.
We apply a variety of genetic and viral transduction techniques to disrupt presynaptic function at the calyx through transgenic mouse models, and expression in neuronal populations using adeno-associated virus (AAV). We use whole cell electrophysiology to record activity from the presynaptic or postsynaptic compartments (and sometimes both!) We complement these recordings with the use of use organic and genetically-encoded probes for functional imaging of essential messengers (Ca2+ ATP, and others).
We are currently interested in understanding the maintenance, distribution, and consumption of energy (ATP) during the development of the calyx synapse, and how these pathways may break down due to aging and/or neurodegenerative disease. We have an active engagement in training future scientists in cell and molecular neuroscience techniques at all levels of study.
Project 2: Neuronal Bioenergetics
In order to facilitate rapid hypothesis testing, we want to translate findings from in vivo experiments in to a more tractable experimental preparation. We use standard primary neuronal cultures to see how neurons respire normally, and how they adapt when faced with metabolic challenges. We find that when neurons are grown in low glucose conditions, energy maintenance is more dependent on mitochondrial function, similar to what is known to happen in the intact brain.
Project 3: What The pH?
An underappreciated change in pH within the synaptic cleft during neurotransmission has the ability to tune synaptic strength. We are using a ratiometric probe (pHusion) to visualize these changes during synaptic activity in central glutamatergic synapses, like the calyx, and at the mouse neuromuscular junction.