Professor, Department of Biology
Ph.D. Stanford University
Professor Emeritus, Yale University School of Medicine
Our laboratory is investigating the cellular mechanisms of cortical function.
How Does the Brain Work?
How does the brain work? Most neuroscientists, including us, became interested in studying the nervous system because of this question. In our laboratory, we reframe this question as: How does an animal gather and process information, make a decision, and act on that decision? It is on this question that our laboratory is attempting to gain insight by examining how an animal performs a decision making task. One example of such a task is detecting a sound embedded in a complex series of sounds and responding to receive a reward.
Optimal State for Neural and Behavioral Performance
One of the first things we noticed was that the ability of animals to perform the task varied rapidly (seconds) and continuously, even though the animals were clearly awake the entire time. We imagine this is similar to either “seminar behavior” where your attention on the lecture waxes and wanes periodically, or “drowsy driving”, where you periodically lose focus on the task at hand. By measuring brain state electrically, and measuring the diameter of the pupil, we found that there is an optimal state for performance of the task, and that this optimal state occurred when the animal is “in the zone”, meaning exhibiting neither too little nor too much arousal. We are now examining the precise neural circuits (e.g. acetylcholine and norepinephrine) that may be responsible for the determination of this optimal state for performance.
Cortical Coding Efficiency:
Stimulation of the cortex with natural stimuli, particularly in the waking, attentive state, gives rise to highly efficient and reliable neuronal responses. We are examining the mechanisms underlying this efficiency and reliability.
Neural Circuits of Brain Processing:
By examining how neurons operate electically, and how they talk to each other chemically, we are uncovering the neural circuits responsible for behavior. We are particularly interested in the neural circuits that transforms a sensory input into a decision that is then implemented in an action. We find great hope that revealing these neural circuits will increase our understanding of not only the ordered, but also the disordered, human brain.
Reimer, J., McGinley, M., McCormick, D.A., Tolias, A. (2016) Pupil fluctuations track changes in noradrenergic and cholinergic activity in the cerebral cortex. Nature Communications, Nov. 8; 7: 13289. Doi: 10:1038/ncoms13289.
Castellucci, G., McGinley, M.J., McCormick, D.A. (2016) Knockout of Foxp2 disrupts vocal development in mice. Scientific Reports, 6: 233305. DOI: 10.1038/srep23305.
Casale, A.E., Foust, A., Bal, T., McCormick, D.A. Cortical interneuron subtypes vary in their axonal action potential properties. (2015) J. Neurosci., 35: 15555-15567.
Zagha, E., Ge, X., McCormick, D.A. (2015) Competing circuits in motor cortex gate motor behavior. Neuron 88: 565-577.
McGinley, M., Vinck, M., Reimer, P., Batista-Brito, R., Zagha, E., Cadwell, C., Tolias, A., Cardin, J., McCormick, D.A. (2015) Waking state: Rapid variations modulate neural and behavioral responses. Neuron 87 (6): 1143-1161.
Salkoff, D.B., Zagha, E., Yuzgec, O., McCormick, D.A. (2015) Synaptic mechanisms of tight spike synchrony at gamma frequency in cerebral cortex. J. Neurosci. 35: 10236-10251.
McGinley, M., David, S., McCormick, D.A. (2015) Cortical membrane potential signature of optimal states for sensory signal detection. Neuron, 87:179-192.
Hadzipasic, M., Tahvildari, B., Nagy, M., Bian, M., Horwich, A.L., and McCormick, D.A. (2014) Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proceedings of the National Academy of Sciences, USA. 111:16883-8.
McCormick, D.A., McGinley, M.J., Salkoff, D.B. (2014) Brain state dependent activity in the cortex and thalamus. Curr. Opin. Neurobiology, 31:133-140.
Zagha, E., McCormick. D.A. (2014) Neural control of brain state. Curr. Opin. Neurobiology, 29:178-86.