BCB/Mathematics Faculty Search:
University of Chicago
Hospitality: 3:45 in 404 Carver Hall
Seminar: 4:10 in 1213 Hoover
Title: Population Coding, Sensory Feedback Processing, and Intrinsic Plasticity in the Cortical Neurons of Songbirds
Abstract: The currency of neuronal communication is spike timing, and the mechanisms for regulating spike timing across populations of neurons remains a central research topic in the neurosciences. We have discovered a novel mechanism for regulating spike timing in populations of neurons, while making whole cell patch recordings in a brain slice preparation that includes the forebrain nucleus HVC of the songbird vocal control system. HVC is a cortical area necessary for song production and includes HVCRA neurons projecting to the motor control pathway and HVCX neurons projecting to the basal ganglia pathway that is involved in evaluating feedback errors. We observed that within each bird, all the HVCX share similar timing features of spike bursts elicited by current injection, but these features varied from bird to bird. Examining what gives rise to this variation, we noted also that spike waveform is invariant within HVCX of a given bird but varies systematically between birds.
We modeled the spike waveforms with an extended Hodgkin-Huxley model that incorporated known principal ionic currents of HVCX, observing little variation within individual animals but enormous variation between animals in the magnitude of several ionic currents, especially (fast sodium) and (calcium-dependent potassium) channels. Manually fit values for these and three other channels (fast potassium, T-type calcium, hyperpolarization-activated inward currents) were confirmed with computationally intensive parameter searches that demonstrated global minima for the models.
The models for spike waveforms also predicted spike burst timing, including data from multiple levels of current injection that were not part of the model fitting. Recordings from individual cells before and after isolation from the network (by blocking fast synaptic transmission) indicated that the within-animal clustering was not dependent on network properties.
We then conducted a set of experiments to understand how this variation is related to behavior. First, we made recordings in sibling animals. In such cases, there was little or no variation between animals. Second, we made recordings in animals that had experienced between four hours and seven days of delayed auditory feedback (DAF), which generates stuttering in the animal and more importantly feedback errors. The data suggest that spike waveforms changed dramatically in as little as four hours, with little to dramatic changes in singing behavior. This represents the first example of a fast physiological signal that carries feedback error information in birdsong learning, and opens a new research program in vocal learning.
Our future directions include mechanistic studies to understand the presumptive trafficking of ion channels or regulation of channel types at the axon hillock that regulates spike waveform and spike timing, systems studies to further connect the results obtained in the slice preparation with data obtained from singing animals, developmental studies to understand when and how the population-wide intrinsic excitation values emerge, and computational studies to understand how auditory feedback rapidly modulates intrinsic excitation in individual neurons.