The function of the nervous system is to produce adaptive behaviors. The selection of a
particular behavior results from attaching value to actions, events, and stimuli based
on their associated outcomes. Our goal is to shed light on the contribution of small
neural circuits, as well as the individual neurons that compose them, to this critical
process of selecting context-appropriate volitional actions. We hope to provide insights
into underlying biological dysfunctions, such as those found in pathological disruptions
of volitional action in Parkinson's disease and addiction.
We begin with the hypothesis that the unique biophysical properties of individual
neurons endow circuits in the brain with distinct computational properties. To understand
the function of a defined neural circuit it is essential to understand not only the
synaptic input and output arrangements but also the integrative properties of neurons at
each point in the circuit. Our lab focuses on understanding the cellular and circuit computations in the dorsolateral striatum of the mouse.
Our work in the lab focuses on two general areas of research:
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Integrative properties of neurons in sensorimotor corticostriatal circuits
Currently we are using patch clamp electrophsiology and two photon microscopy to study the spatial and temporal determinants of dendritic integration in principle neurons of the dorsolateral striatum.
We primarily focus on the integration of glutamatergic synaptic inputs in order to understand how striatal neurons can transform corticostriatal and thalamostriatal inputs.
In collaboration with other labs at Janelia Farm we are developing genetic and chemical tools to characterize the integrative properties of striatal neurons and study the functional architecture of corticostriatal and thalamostriatal circuits.
These experimental approaches are complemented by the development of computational models that both test hypotheses generated from our recordings as well as producing testable predictions for future experiments.
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The role of the dorsolateral striatum in reinforcement learning
Our long term goal is to understand how the integrative properties of striatal neurons determine the patterns of activity in corticostriatal circuits that underly reinforcement learning paradigms.
One approach we are currently pursuing is to develop techniques to make dense extracellular and intracellular electrophysiological recordings from awake, behaving mice during acquisition and performance in an operant conditioning paradigm.
In parallel with our studies in vitro we hope that these recordings will help to clarify the contribution of dendritic integration in striatal neurons to the observed circuit-level patterns of activity.
In collaboration with several groups at Janelia Farm we are drawing upon the expertise of the Instrument Design & Fabiraction group to design and build custom electronics, electrodes and recording systems.
We hope to contribute to a toolkit for electrophysiological recordings that will benefit the larger neuroscience community.
In the long term, it is our hope that by developing multiple experimental approaches (optical imaging, intra- and extracellular electrophysiology, and computational modeling) to study striatal circuits that we will begin to provide a detailed mechanistic account of how the selection and performance of adaptive behaviors is implemented in the brain.
Our work has previously been supported supported by the National Science Foundation and the National Institutes of Health. Currently, our research is supported by the Howard Hughes Medical Institute.
