It has been appreciated for over 30 years that visual experience during an early postnatal critical period of development produces permanent modifications of the connectivity, physiology and function of the visual cortex. Besides the obvious relevance of this neural plasticity to the development of visual capabilities in humans and animals, it seems likely that similar processes from the basis for some forms of learning and memory in the adult brain. Considerable progress has been made in identifying the specific changes in visual cortex that result from rearing the animals in different environments, but the detailed mechanisms that underlie these modifications have remained elusive. Recently, however, advance in understanding the receptor mechanisms that mediate synaptic excitation and inhibition in the visual cortex during development have provided an exciting new opportunity to investigate the mechanisms of experience- dependent brain modification. The long-term goal of this project is to elucidate these molecular mechanisms of experience-dependent cortical plasticity. It is hypothesized that naturally occurring synaptic enhancements employ the mechanisms that underlie long-term synaptic potentiation (LTP), a type of plasticity that can be elicited in cortical synapses by tetanic electrical stimulation. To examine this hypothesis, a preparation has been introduced in which LTP can be elicited in the geniculo-cortical projection in vivo..
The aims of the research are (1) to characterize the laminar, spatial and temporal characteristics of LTP induced in visual cortex by tetanic stimulation of the lateral geniculate nucleus (LGN); (2) to investigate the consequence of LTP induction in vivo on visually evoked potentials and visual cortical receptive fields in normal and dark-reared (DR) animals, and to compare these with the effects of light exposure in dark-reared animals; (3) to investigate the interaction of naturally occurring synaptic enhancement and LTP in the visual cortex in vivo;; and (4) to document structural changes which follow LTP induction in vivo and compare these with the changes that follow induction of synaptic enhancement caused by light exposure (LE) in dark-reared animals. This experiment promises to establish, for the first time in any light exposure (LE) in dark-reared animals. These experiments promise to establish, for the first time in any system, which LTP and naturally occurring synaptic plasticity utilize common mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY012309-01
Application #
2696501
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Brown University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
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Chubykin, Alexander A; Roach, Emma B; Bear, Mark F et al. (2013) A cholinergic mechanism for reward timing within primary visual cortex. Neuron 77:723-35
Cho, Kathleen Ka; Bear, Mark F (2010) Promoting neurological recovery of function via metaplasticity. Future Neurol 5:21-26
Coleman, Jason E; Nahmani, Marc; Gavornik, Jeffrey P et al. (2010) Rapid structural remodeling of thalamocortical synapses parallels experience-dependent functional plasticity in mouse primary visual cortex. J Neurosci 30:9670-82
Smith, Gordon B; Bear, Mark F (2010) Bidirectional ocular dominance plasticity of inhibitory networks: recent advances and unresolved questions. Front Cell Neurosci 4:21
Khibnik, Lena A; Cho, Kathleen K A; Bear, Mark F (2010) Relative contribution of feedforward excitatory connections to expression of ocular dominance plasticity in layer 4 of visual cortex. Neuron 66:493-500
Cooke, Sam F; Bear, Mark F (2010) Visual experience induces long-term potentiation in the primary visual cortex. J Neurosci 30:16304-13
Yoon, Bong-June; Smith, Gordon B; Heynen, Arnold J et al. (2009) Essential role for a long-term depression mechanism in ocular dominance plasticity. Proc Natl Acad Sci U S A 106:9860-5
Cho, Kathleen K A; Khibnik, Lena; Philpot, Benjamin D et al. (2009) The ratio of NR2A/B NMDA receptor subunits determines the qualities of ocular dominance plasticity in visual cortex. Proc Natl Acad Sci U S A 106:5377-82
Gavornik, Jeffrey P; Shuler, Marshall G Hussain; Loewenstein, Yonatan et al. (2009) Learning reward timing in cortex through reward dependent expression of synaptic plasticity. Proc Natl Acad Sci U S A 106:6826-31

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