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We are interested in the
mechanisms underlying spontaneous activity in the developing nervous
system and the role this activity plays in the construction of neuronal
circuits. There are several examples throughout the developing vertebrate
nervous system, including the retina, spinal cord, hippocampus and
neocortex, where immature neural circuits generate activity patterns
that are distinct from the functioning adult circuitry. It has been
proposed that these transitional circuits provide the “test patterns”
necessary for normal development of the adult nervous system.
We study spontaneous activity
in the immature mouse and rat retina. Mice are born with their eyes
closed. Light responses are first detected at postnatal day 10 (P10)
and their eyes open at P14. During these first two postnatal weeks,
immature retinal circuits spontaneously generate propagating bursts
of action potentials termed retinal waves. During
this same postnatal period, there is tremendous amount of
development within the visual system, including formation of retinal
circuits that mediate various light responses, as well as sculpting
of retinal projections to their primary targets in the brain. Hence,
the developing visual system is a premier model system for studying
the role of spontaneous activity in the development of functional
circuits.
We use a combination of
electrophysiology, imaging, and anatomical techniques to address three major
questions:
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What are the cellular mechanisms underlying
retinal waves?
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What is the role of retinal waves in the development of retinal projections to the brain?
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How do motion sensitive circuits arise during development?
How are neural circuits wired up during development to perform computations? A classic neural computation is that of detecting the direction of motion of an object within the visual scene. Direction-selective cells are found in the retina and function as the first component of the reflex that stabilizes the visual image on the retina when an animal is in motion. Direction-selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite direction. This computation relies upon an asymmetric set of connections between inhibitory neurons onto direction selective cells as well as non-linearities in the cells themselves. We use a combination of single- and multielectrode recordings and two-photon imaging to determine the mechanisms that underlie the development of these asymmetric circuits.
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