The goal of our laboratory is to understand the mechanisms that underlie synaptic plasticity in the developing and mature mammalian central nervous system. We use a combination of tools, including electrophysiological, in vitro and in vivo optical imaging methods, along with genetically altered mouse strains, optogenetics and pharmacogenetics to examine the regulation of synaptic circuits in the visual system.
One area of our research focuses on the establishment and refinement of synaptic circuits during development. We have characterized, using electrophysiological techniques, the convergence of the retinogeniculate synapse during development as multiple inputs are eliminated and remaining synaptic inputs strengthened. In addition, we have uncovered an experience-dependent critical period at this synapse during which connections can be re-wired late in development. Our studies show that developmental refinement results in an exquisite logic in the arrangement of retinal ganglion cell boutons tuned to different features of the visual space converging onto the same thalamic neuron. We are interested in identifying the cellular and molecular mechanisms that underlie this developmental process. We are taking advantage of mouse mutants and viral-mediated circuit manipulations to elucidate the roles of specific molecular cues and plasticity mechanisms.
In a related line of research, we are studying how thalamic relay neurons integrate different lines of visual information and identifying the synaptic mechanisms by which this information is transformed into the output of the thalamocortical neurons. We are addressing several questions: (1) what are the rules that decode convergent retinal information into thalamocortical output, (2) how do ascending neurotransmitter systems from the brainstem regulate the strength of the retinogeniculate synapses and sensory processing, (4) how do feedback circuits from the cortex and thalamic reticular nucleus influence the convergence of different lines of visual information, (3) how sensory experience can alter the transformation of convergent retinal information to thalamocortical output.
The results of these studies will help advance our understanding of how disruption of proper synaptic circuit development can lead to neurodevelopmental disorders such as autism spectrum disorders, intellectual disabilities and epilepsy.
F.M. Kirby Neurobiology Center
Center for Life Science, 12th Floor
3 Blackfan Circle
Boston, MA 02115