These experiments have two goals: First, to test the hypothesis that the organization of cerebral neocortex is malleable in adult mammals and second to test the idea that cortical reorganization is regulated by certain widespread cortical inputs. The rat motor cortex (MI) has been chosen as a model for these studies because it is possible to assess changes both in sensory representation and in motor output in this system, and it is also possible to relate MI reorganization to modification in the cortical control of movement. Specifically, the proposed experiments will identify the types of adaptive responses that occur in rat MI following a peripheral injury (forelimb amputation). MI reorganization will be evaluated first with intracortical microstimulation and somatic sensory receptive field mapping techniques. The extent of reorganization will be compared in neonatally or adult-amputated rats to identify the potential limits of reorganization in this system. Preliminary data suggest that MI reorganization occurs with early postnatal amputation. Next, the location and extent of reorganization will be further tested by using axonal tracers to examine connectional changes induced by forelimb amputation. Finally, topographic reorganization will be studied after noradrenergic (NA) or cholinergic (ACh) inputs to MI are eliminated. These experiments should help to localize sites of reorganization and should further clarify the role of these widespread inputs in regulating cortical organization. These experiments will provide important new information concerning the flexibility of the relationship between the cortex and the somatic periphery, and the results may suggest strategies for enhancing or suppressing cortical responses to peripheral injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022517-02
Application #
3405016
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Brown University
Department
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Sanes, J N; Donoghue, J P (2000) Plasticity and primary motor cortex. Annu Rev Neurosci 23:393-415
Hess, G; Donoghue, J P (1999) Facilitation of long-term potentiation in layer II/III horizontal connections of rat motor cortex following layer I stimulation: route of effect and cholinergic contributions. Exp Brain Res 127:279-90
Rioult-Pedotti, M S; Friedman, D; Hess, G et al. (1998) Strengthening of horizontal cortical connections following skill learning. Nat Neurosci 1:230-4
Sanes, J N; Donoghue, J P (1997) Static and dynamic organization of motor cortex. Adv Neurol 73:277-96
Donoghue, J P (1997) Limits of reorganization in cortical circuits. Cereb Cortex 7:97-9
Hess, G; Donoghue, J P (1996) Long-term depression of horizontal connections in rat motor cortex. Eur J Neurosci 8:658-65
Hess, G; Aizenman, C D; Donoghue, J P (1996) Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex. J Neurophysiol 75:1765-78
Hess, G; Krawczyk, R (1996) Cholinergic modulation of synaptic transmission in horizontal connections of rat motor cortex. Acta Neurobiol Exp (Wars) 56:863-72
Hess, G; Donoghue, J P (1996) Long-term potentiation and long-term depression of horizontal connections in rat motor cortex. Acta Neurobiol Exp (Wars) 56:397-405
Castro-Alamancos, M A; Donoghue, J P; Connors, B W (1995) Different forms of synaptic plasticity in somatosensory and motor areas of the neocortex. J Neurosci 15:5324-33

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