The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.
This award will support a twenty-four-month research fellowship by Dr. Bilal Haider to work with Dr. Matteo Carandini at University College London in the United Kingdom.
This project tests the idea that activity patterns in the cerebral cortex play a strong if not decisive role in when and how cortical neurons respond to sensory stimulation. The host and PI first characterize, then quantitatively predict, and finally causally manipulate patterns of cortical neural population activity during visual stimulation. These investigations utilize advanced electrophysiological and optical techniques, respectively, to monitor and manipulate excitatory and inhibitory cortical activity. Further, these investigations are performed in the mouse visual system, a preparation which is uniquely amenable to combined electrical and optical techniques, and which is emerging as a model of choice for advanced neurophysiological recording during behavior. Their investigations extend the study of visual processing to the most utilized model organism for mammalian neuroscience, and provide significant potential for development and implementation of advanced electrical and optical technologies in the intact brain.
More generally, how do external stimuli and internal activity states interact at the neuronal level to serve sensory processing? While some insight has been gained into the responses of cortical neurons to sensory stimulation, and also gained insights into the interactions of cortical neurons with each other, full understanding of the dynamic interaction between sensory inputs and ongoing cortical activity remains elusive. It has often been suggested that the response properties of cortical neurons are largely inherited from incoming sensory inputs, rather than by the surrounding assembly of cortical neurons. By directly manipulating activity patterns in the cortex while also manipulating aspects of visual stimulation, they can assess the contributions of internally generated versus externally elicited activity that underlies sensation.
How does the brain respond to sensory stimuli, and how do these responses change according to behavioral state? Answering these questions requires knowledge of the electrical signals generated by brain cells (neurons) during sensory stimulation. These electrical signals have been most thoroughly investigated for neurons in the visual system of felines and non-human primates. Visually evoked responses are typically recorded from the outside of these neurons, by monitoring their output signals (action potentials) in response to controlled visual stimulation. Monitoring the input signals (synaptic potentials) occurring inside an individual neuron is more technically challenging, and requires intracellular recording. In the current project, we have performed intracellular recordings in the mouse visual cortex during different behavioral states, and recorded visual responses to stimuli presented across large regions of visual space. During inactive behavioral states, visual responses typically last far longer than the duration of the visual stimulus, and can be elicited from many parts of the visual field. Under these conditions, excitatory and inhibitory inputs are nearly equal in magnitude, and match each other for all stimuli presented across visual space. However, during active behavioral states, inhibitory inputs are greatly enhanced compared to excitatory inputs, and visual responses are consequently restricted in spatial extent and temporal duration. These results suggest that during active behavioral states, sensory responses are short-lasting and spatially specific primarily due to enhanced inhibition. The results from the current project open significant avenues for investigating a variety of visual circuit functions and dysfunctions in behaving mice, the most widely utilized and genetically modifiable mammalian species.
