O’Connor lab @ Hopkins

 
 

How do brain dynamics give rise to our sensory experience of the world? We work to answer this question by taking advantage of the fact that key architectural features of the mammalian brain are similar across species. This allows us to leverage the power of mouse genetics to monitor and manipulate genetically and functionally defined brain circuits during perception. We train mice to perform simple perceptual tasks. By using quantitative behavior, optogenetic and chemical-genetic gain- and loss-of-function perturbations, in vivo two-photon imaging, and electrophysiology, we assemble a description of the relationship between neural circuit function and perception. We work in the mouse tactile system to capitalize on an accessible mammalian circuit with a precise mapping between the sensory periphery and multiple brain areas.


We have a long-standing interest in the dynamic gain control and routing, or gating, of sensory information. A striking aspect of perception is that it is limited in bandwidth. Let’s say you are following a talk show on your car radio until you realize you are about to miss your exit, among heavy highway traffic. After you manage to exit, you realize you have no idea what happened on the radio for the last half minute. The hair cells in your inner ear did not stop transducing sound. Somehow this perceptual gap arose because you shifted your attention from the radio to driving. Sensory-evoked action potentials must be selected according to their relevance to behavioral goals; not all can drive perception and behavior at once. However, the circuit and cellular mechanisms that select and route action potentials to ultimately drive perception and adaptive behavior remain mysterious. A current focus of the lab is to address this problem using a simple model: gain control of the translaminar flow of excitation through the cortical column. In particular, we are examining how a dominant thalamorecipient neuron type in early sensory cortex---the layer 4 stellate cell---is able to drive output projection neurons in layers 2/3 and 5, as a function of behavioral state and sensory expectation. These and related experiments will reveal the circuit and cellular mechanisms by which behavioral goals (such as understanding the radio show or navigating through traffic) regulate the propagation of action potentials along the causal chain from sensory transduction to behavior.


By unraveling circuits for touch perception in the mouse, we expect to gain key insights into principles of mammalian brain function, and to provide a framework to understand how circuit dysfunction ultimately causes mental and behavioral aspects of neuropsychiatric illness.