From Jan Willem de Gee and Tobias Donner.
We recently hosted Dr. Matthew G. McGinley as a Visiting Researcher funded by the SFB936 program, currently running in its second phase here at the University Medical Center Hamburg-Eppendorf. Our reason to invite Matt was two-fold: (i) to share in our SFB Methods Academy his expertise on whole cell recordings and two-photon microscopy in awake (behaving) rodents, and (ii) to further develop collaborations between the Donner and McGinley labs aimed at integrating measurements performed in different species and at different scales.
Matt convincingly argued that the state of the brain is constantly changing, that these changes in internal state (such as arousal and attention) are in large part mediated by neuromodulatory signals, and that they profoundly impact what we perceive and how we act on it.
In recent work, he and collaborators found that, in mice, the pupil diameter is a sensitive readout of noradrenergic and cholinergic activity (as measured by two-photon microscopy) (Reimer et al., 2016). Specifically, his work revealed that the pupil tracks neuromodulatory signals at multiple time-scales: rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons.
McGinley then went on to show that such neuromodulation dramatically changes the neural and behavioral responses to sound (McGinley et al., 2015a; 2015b). Specifically, this work revealed a cellular and network basis for the classic inverted-U relationship between arousal and performance (Yerkes and Dodson, 1908): at intermediate arousal (as measured by pupillometry), behavioral performance was most rapid, accurate and least biased, and sensory responses at both the spiking and subthreshold membrane potential levels (as measured by whole cell recordings) were largest and most reliable.
Matt ended his inspiring talk by outlining the future directions of his lab in the Department of Neuroscience at Baylor College of Medicine and Duncan Neurological Institute in Houston, USA. The central question Matt aims to provide an answer to is how the motivational state of an animal interacts with neuromodulatory systems to exert top-down control of brain state, perception, and behavior. Matt approaches this question with a range of high-tech tools including whole cell recordings, two-photon microscopy, optogenetics, ECoG recordings and pupillometry in mice during behavior that is under tight stimulus control (with psychophysics).
Finally, we have used Matt’s visit to in person finalize a first joint manuscript (more about that in a later post) and flesh out further coordinated work of both labs. Jan Willem de Gee will take up a position as postdoctoral researcher in the McGinley lab in September 2018, and in that capacity act as an interface between our two labs. We have high expectations for these collaborative efforts, so stay tuned!
Thank you, Matt, for taking the effort to visit us in Hamburg!
McGinley, M.J., David, S.V., McCormick, D.A., 2015a. Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection. Neuron 87, 179–192. doi:10.1016/j.neuron.2015.05.038
McGinley, M.J., Vinck, M., Reimer, J., Batista-Brito, R., Zagha, E., Cadwell, C.R., Tolias, A.S., Cardin, J.A., McCormick, D.A., 2015b. Waking State: Rapid Variations Modulate Neural and Behavioral Responses. Neuron 87, 1143–1161. doi:10.1016/j.neuron.2015.09.012
Reimer, J., McGinley, M.J., Liu, Y., Rodenkirch, C., Wang, Q., McCormick, D.A., Tolias, A.S., 2016. Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex. Nat Commun 7, 13289. doi:10.1038/ncomms13289
Yerkes, R.M., Dodson, J.D., 1908. The relation of strength of stimulus to rapidity of habit‐formation. Journal of Comparative Neurology and Psychology 18, 459–482. doi:10.1002/cne.920180503