Johns Hopkins School of Medicine

Functional Organization of Local Circuits of the Neocortex

The neocortex represents a massive interconnected network of neurons that generates perception and action. Indeed, most synaptic inputs onto neocortical neurons come from other neocortical neurons. Our research takes a bottom-up approach to understanding how these circuits integrate incoming information and generate the cortical outputs that govern perception, thought and action. Our strategy is to combine physiological approaches with anatomical and genetic techniques for identifying cell populations and pathways to define the synaptic interactions among different classes of cortical neurons and to understand how long-range feedforward and feedback inputs are integrated within these circuits. For example, the cortex must integrate a variety of long-range inputs including feedforward activation from the sensory periphery and top-down influences reflecting internal states like attention to generate our perception of the world. By activating these different long-range pathways, we can begin to understand how cortical circuits integrate these diverse inputs. Similarly, each class of output neuron in the cortex drives a different set of brain regions to produce our actions and internal states. By identifying the synaptic partners of functionally identified output neurons of the cortex and characterizing the dynamic properties of their synaptic connections, we can begin to understand the computations taking place within the cortex. Our experimental approaches include (1) simultaneous patch-clamp recordings from multiple neurons in cortical slices, (2) in vivo anatomical and genetic labeling of specific cell populations with fluorescent markers, (3) optical monitoring of neuronal activity in brain slices and (4) optical stimulation and inhibition of long-range axons and specific cortical cell types expressing light-gated channels like channelrhodopsin-2. Using these types of approaches, our long-term goal is to understand how cortical circuits give rise to cortical activity and ultimately generate perception and behavior.