In the first few years of life, humans tremendously expand their behavioral repertoire and gain the ability to engage in complex, learned, and reward-driven actions. Similarly, within a few weeks after birth mice can perform sophisticated spatial navigation, forage independently for food, and engage in reward reinforcement learning. Our laboratory seeks to uncover the mechanisms of synapse and circuit plasticity that permit new behaviors to be learned and refined. We are interested in the developmental changes that occur after birth that make learning possible as well as in the circuit changes that are triggered by the process of learning.  Lastly, we examine how perturbations of these processes contribute to human neuropsychiatric disorders such as Tuberous Sclerosis Complex and Parkinson’s Disease. Take a video tour of the lab and building (actually a music video produced for Chairlift filmed, in part, in our lab).

Manipulating circuits and synapses

Studying synapses and circuits in situ requires methods to probe cells and subcellular elements within complex brain tissue. These techniques include: 2-photon microscopy laser scanning microscopy to monitor cell structure and the activation of signaling cascades; photoactivation of biologically relevant molecules to turn signaling cascades on and off; and optogenetics to manipulate the activity of genetically-defined cell populations.

Autism and the synapse

Many childhood neuropsychiatric diseases, including several genetic forms of autism, result from mutations in proteins found at synapses. How these mutations alter the function synapses and ultimately brain circuits is largely unknown. We are addressing these questions using reductionist approaches to examine the function of each synapse and integrative approaches to examine the impact of synaptic perturbations on circuit function.

Basal Ganglia & Behavior

The basal ganglia process information from the cerebral cortex and thalamus to control locomotor behavior. The ability to generate coordinated movements and to associate action with reward require the basal ganglia. We are examining the functional circuitry of the basal ganglia and the relationship between activity and behavior in mice that have been taught to perform motor actions for water rewards.

Howard Hughes Medical Institute
Harvard Medical School