We are interested in understanding how the specific cell types in motor cortex are connected, and how these specific connections enable motor cortex to control movement.
In the mammalian brain, different cortical areas are specialized for different functions. Motor cortex is specialized for the planning, initiation, control, and learning of movements. However, the precise computations performed in motor cortex circuits are not well understood. In particular, the specific circuit connections of defined cell types in motor cortex are not well described, how specific connections drive neuronal firing is not known, and which connections change strength during learning is also unknown.
Progress has been limited since there were a variety of intermingled neuronal types in each cortical area and until recently it was not always possible to independently stimulate specific local and long-range pathways. Fortunately, the tools needed to define cortical circuits are being rapidly developed, including (a) means to reliably define and manipulate specific cell types and (b) methods to excite and quantify specific inputs. New transgenic lines, including some I am playing a role in characterizing, will label specific neuron populations in mouse neocortex, including specific subtypes of excitatory pyramidal neurons and inhibitory interneurons. This will enable targeted recording and excitation of specific cell types. Different cell types are believed to play distinct roles in the local circuit, so understanding their specific inputs will help explain the specific response properties of each cell type. New circuit mapping approaches using optical and genetic methods to render specific populations of presynaptic neurons excitable make it possible to quantify the connectivity of local and long-range inputs to different cortical cell types. Furthermore, I have begun to extend circuit mapping methods to comparing the strengths of multiple inputs onto the same neuron, independently stimulating two inputs using distinct colors of light. This will address whether individual neurons specialize to preferentially receive certain types of input.
The results of both projects will leave us well positioned to take advantage of cell-type specific transgenic mice and modern circuit mapping methods to understand connectivity in motor cortex. In the short term, I intend to: (1) Understand how feedforward inhibition is recruited in motor cortex by distinct cortical and thalamic inputs. Specifically, we seek to know whether these inputs recruit the same subtypes of inhibitory interneurons (such as parvalbumin and somatostatin expressing interneurons), whether these inputs excite the same individual cells, and what rules govern the magnitude of feedforward excitation and inhibition from cortical and thalamic inputs to motor cortex. (2) Examine where in the cortical circuit the inputs from distinct motor thalamic nuclei are combined. This will help to address how subcortical regions involved in motor learning and action selection, relaying input via motor thalamus, act together to influence the output of motor cortex. (3) Understand how specific cell types of primary sensory areas excite specific pyramidal cell types in primary motor areas.
Currently, the lab uses mouse motor and sensory cortex as model system. This allows us to take advantage of many cell-type specific mouse lines as well as optogentic tools developed for mice. Techniques we use include stereotaxic surgery, use of AAV for expressing a variety of optogenetic tools and fluorophores, mouse brain slice and laser-scanning microscope to map circuits, and anatomical techniques for reconstructing circuits. We will continue to develop new techniques to address questions of the neural basis for motor control.