Detailed Biography:

Research Interest:

Cellular and molecular aspects of neural signaling

Our brains accomplish (or sometimes fail at) their jobs by generating coordinated patterns of electrical signals in groups of nerve cells (neurons). Research in my laboratory focuses on the general question of how this coordination occurs. Circuits, single connections (synapses) and electrical properties particular to individual neurons combine to allow large groups of neurons to generate the specific firing patterns that ultimately result in thoughts, feelings and behaviors. In an effort to understand how the brain works at such a nuts and bolts level, we concentrate mainly on the cerebellum, a brain region responsible for coordinating movement. The cerebellum is a principal brain area involved in learning how to make precise and sequenced movements such as are required for playing a musical instrument or excelling at a sport. Yet the cerebellum is critical for even ‘automatic’ movements such as postural adjustments to maintain balance or eye movements that allow redirection of gaze. Diseases of the cerebellum, collectively termed ataxias, degrade the ability to make coordinated movements and impair the formation of motor memories, memories that are necessary to improve coordination with practice. Our lab combines classical neurophysiological and advanced optical approaches to study how circuits of cerebellar neurons hone movements and store motor memories. Techniques include photolysis of caged compounds in intact brain circuits, optical manipulation of various photosensitive targets, patterned illumination for stimulating neuronal circuits, and diffraction-illuminated spot imaging of membrane potential from single neurons using optical voltage sensors. Recently we have developed an optogenetic approach to manipulate the activity of groups of cerebellar neurons and thereby evoke movements which can be studied with high speed video and motion tracking algorithms. By pairing specific patterns of neuronal activity with sensory stimuli one can experimentally induce the formation of new motor memories. These and related experiments allow us to test ideas about how memories are formed and stored, and also to interrogate cerebellar circuits in mouse models of ataxia in order to probe the circuit basis for these pathologies. Finally, in collaboration with Ben Novitch’s lab at UCLA and Clive Svendsen’s lab at Cedars Sinai we have been recording from stem cell derived motor neurons in order to understand fundamental mechanisms of motor neuron diseases and facilitate drug discovery to treat these disorders.