The sensory representation of causally controlled objects
The experience of agency is integral to our sense of self and responsibility, and its dysfunction in a number of psychopathologies can have devastating social effects. Representations are fundamental to the idea of computation, and presumably underpin how the brain performs the seemingly alchemical transformation from ionic impulse to meaning. In this paper, we investigated the interplay of agency with sensory representations in the brain. The cortex transforms a series of representations of the sensory world in building sensory percepts. Only recently have scientists been able to study how an animal’s internal states, goals and actions feed back to shape this sensory simulcra, but little is known about how having a sense of control over an outside object affects how it is perceived.
The ability to exert intentional control over external objects is informed by our sensory experience of them, in a continuous dialogue between action and perception. To investigate how control is represented at the sensory level, we devised an optical brain machine interface (BMI) task that enabled mice to guide a visual cursor to a target location for reward, using activity in brain areas recorded with widefield calcium imaging.
Mapping multi-scale cortical networks
How do neurons in the cortex share information on local and global scales? The cortex is richly interconnected, and while fMRI studies have indicated that distant brain areas are fluidly coupled, we don't know how these dynamics are achieved at a cellular level over the static architecture of axonal projections. We recorded from individual neurons while imaging activity across the dorsal cortex to determine the functional coupling of individual neurons to activity in global cortical networks. This revealed that a change in behavioral state driven by locomotion reconfigures how individual neurons participate in distributed cortical ensembles. Read paper here.
The optical brain-machine interface
How does a network control itself? Brain-machine interfaces are not only promising for neurological applications, but also powerful for investigating neuronal ensemble dynamics during learning. Optical readouts of brain activity enable us to non-invasively monitor the local network while animals learn a BMI task to understand how volitional control of a network is achieved. We trained mice to operantly control an auditory cursor using spike-related calcium signals recorded with two-photon imaging in motor and somatosensory cortex. Read paper, or see Nature Neuroscience News and Views
Unlearning chronic pain
The power of the brain lies in its ability to learn, and it retains this capacity throughout adulthood. Yet this very ability is the basis for many neurological diseases. Pathological states can be learned by the network: for example, elevated activity learned by various pain pathways result in chronic pain sensation, even in the absence of noxious stimuli. But what can be learned can be unlearned. This proposal of a novel therapy was awarded the Regeneron Prize for Innovation in Biomedicine for utilizing the brain’s endogenous capacity for learning to re-train healthy function in neuropathic pain disorders.
Sparse coding in somatosensory cortex
Neurons fall along a spectrum of responsiveness, but what factors determine a neurons’ participation in network activity? We found that stimulus-evoked response probability correlated strongly with spontaneous firing rate, but weakly with tuning properties, indicating a spectrum of inherent responsiveness across pyramidal cells. Neurons projecting to higher cortical areas differed in whisker tuning and responsiveness, and carried different amounts of stimulus information. Read more here and here.
Optical blood oxygenation monitor
Sudden Unexpected Death in Epilepsy (SUDEP) is a devastating risk for seizure sufferers, and the leading cause of death in patients with refractory epilepsy. While there is no single underlying cause in all SUDEP cases, hypoxia is of particular interest, and this intervention has implications for a wide range of disorders. Read more here and here.
Publication list
Clancy, K., Mrsic-Flogel, T. The sensory representation of causally controlled objects. Neuron, 2021.
Clancy, K., Orsolic, I., Mrsic-Flogel, T. Locomotion-dependent remapping of distributed cortical networks. Nature Neuroscience, 2019.
Clancy, K., Rao, A., Feldman, D. Structure of the sparse spike code in layer 2 of rodent somatosensory cortex. J Neuroscience, 2015.
Clancy, K., Koralek, A., Costa, R., Feldman, D., Carmena, J. Volitional modulation of optically recorded calcium signals for neuroprosthetic control. Nature Neuroscience, 2014. See Nature Neuroscience 'News and Views'
Elstrott, J., Clancy, K., Jafri, H., Akimenko, I., Feldman, D. Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in whisker somatosensory cortex. J. Neurophys., 2014.
Pasachoff JM, Souza SP, Babcock BA, Ticehurst DR, Elliot JL, Person MP, Clancy KB, Roberts LC, Hall DT, and Tholen DJ. The Structure of Pluto's Atmosphere from the 2002 August 21 Stellar Occultation. The Astronomical Journal, v. 129(3), p. 1718-1823, 2005.
Elliot, J. L., Kern S.D., Clancy K.B., Gulbis A.A. S., Millis R.L., Buie M.W., Wasserman L.H., Chiange E.I. Jordan A.B., Trilling D.E., Meech K.J. 2005, The Deep Ecliptic Survey: A Search for Kuiper Belt Objects and Centaurs. II. Dynamical Classification, the Kuiper Belt Plane, and the Core Population, The Astronomical Journal, v. 129(2), p. 1117-1162.
Elliot, JL, Ates A, Babcock BA, Bosh AS, Buie MW, Clancy KB, Dunham EW, Eikenberry SS, Hall DT, Kern SD, Leggett SK, Levine SE, Moon DS, Olkin CB, Osip DJ, Pasachoff JM, Penprase BE, Person MJ, Qu S, Rayner JT, Roberts LC, Salyk CV, Souza SP, Stone RC, Taylor BW, Tholen DJ, Thomas-Osip JE, Ticehurst DR, Wasserman LH. The recent expansion of Pluto's atmosphere. Nature, v. 424(6945), p. 165-168., 2003.