Bridging the gaps between molecular, cellular, and systems neuroscience...
Synaptic organization of cortical circuits.
Neuronal circuits in the neocortex can be divided into feed-forward pathways, which typically carry sensory information from the periphery, and feed-back pathways, which carry top-down contextual signals important for attention and executive control. We are exploring how these information streams are processed by single neurons. In acute brain slice preparations, we combine electrophysiology, optogenetics, 2-photon calcium imaging, and focal glutamate uncaging to study the functional distribution and integration of targeted synaptic inputs within cortical dendrites. In vivo, we combine 2-photon imaging with optical and genetic manipulations to understand the behavioral roles of circuits in the visual cortex.
Development, organization, and function of inhibitory GABAergic synapses.
GABAergic inhibition plays a critical role in the development and maintenance of cortical circuits, and a growing body of evidence links inhibitory dysfunction to neuropsychiatric illnesses including autism and schizophrenia. In our lab, we combine dendritic imaging with optogenetic manipulation of targeted interneuron populations to explore the development, function, and plasticity of GABAergic synapses. In additon, we are studying the contribution of early experience to GABAergic circuit organization and the consequences for behavior in adulthood.
Neuromodulation: providing functional flexibility to cortical circuits.
Adaptive behavior over the life of an organism requires a nervous system with sufficiently stable wiring to support long-term memory but plastic enough to adjust to rapid changes in environmental context. Much of this dynamic flexibility is provided by neuromodulators, such as dopamine, acetylcholine, and norepinephrine, which influence the strength of synaptic transmission. We use a combination of approaches to study the cellular mechanisms and functional actions of neuromodulation in both acute slice preparations and in vivo.
Exploring circuit and synaptic disruption in models of neuropsychiatric illness.
A large body of evidence now suggests that disruption of synaptic transmission and subsequent dysfunction of neuronal circuits contributes to the pathophysiology of neuropsychiatric disorders such as schizophrenia and autism. We are actively investigating how genetic alteration of specific neuronal classes in the neocortex contributes to behavioral phenotypes in mouse models of autism spectrum disorders such as Tuberous Sclerosis Complex (TSC).