Visualizing long-term circuit plasticity
Changes in neural circuit activity play a critical role in many aspects of nervous system function throughout life, from development to learning and the progression of disease. We study how neural circuits of the mouse neocortex encode the sensory environment, and how the rules of encoding undergo plasticity during altered sensory experience. We use chronic in vivo imaging techniques to measure functional changes of both large-scale activity maps and the underlying local neuronal populations. Two-photon imaging of neurons expressing genetically encoded activity sensors allows us to repeatedly measure activity of the exact same neurons over days and weeks as plasticity takes place. Defining the logic of functional plasticity within cortical circuits has implications for understanding how the brain changes under pathological conditions and for identifying cellular targets to enhance functional recovery.
We are interested in: 1) The roles of genetically and anatomically defined types of cortical neurons in sensory processing and plasticity. What are the relative contributions of excitatory and inhibitory neurons to the expression of plasticity? Do microcircuits of excitatory neurons undergo specific forms of plasticity depending on their axonal projection targets? 2) Effects of learning on sensory and sensorimotor processing. Do learning and sensory deprivation impact ensemble activity by similar mechanisms? How is local and large-scale neural circuit activity modified over weeks during the transition from learning to memory to forgetting? We approach these questions by training mice to learn and perform simple behaviors during imaging. 3) Alteration of neuronal circuit function by injury and disease. Based on knowledge gained in ongoing work, we hope to test predictions of the effects of injury and disease on specific aspects of neuronal circuit function.
Chronic in vivo imaging of neuronal ensembles
Neurons in mouse neocortex expressing a genetically encoded activity sensor (Right) imaged through a chronic cranial window (Left). Field of view marked by square.