Changes in afferent activity to a sensory neuron can lead to changes in the neuron's receptive field. In the somatosensory system, subcutaneous injection of lidocaine into a neuron's receptive field results in marked reorganization of the receptive field, such that within minutes the neuron begins to respond to regions of skin outside the original receptive field. This process might reflect a mechanism by which the nervous system rapidly adapts to changes in the sensory environment (for example, tactile scanning of a surface might rapidly lead to reduced receptive field sizes and thus enhanced discriminability). Because it happens rapidly, receptive field reorganization appears to involve an """"""""unmasking"""""""" of existing, ineffective synapses rather than sprouting of new connections. The neural mechanisms that underlie this synaptic unmasking are unknown. The proposed research will test a new model regarding the mechanism of unmasking: a decline in afferent activity changes the membrane conductance of a neuron such that distal synapses become """"""""unmasked,"""""""" and the neuron's receptive field enlarges. Specifically, the reduction in ongoing, spontaneous synaptic activity produced by subcutaneous lidocaine injection results in closure of membrane ion channels on the soma and proximal dendrites. This reduces membrane conductance and increases input resistance, increasing the electrotonic size of the neuron, As a result, previously ineffective synapses on distal dendrites become effective in producing membrane potential changes at the soma. This model will be tested in vivo on rat dorsal horn neurons by 1) producing RE reorganization while measuring input resistance in whole cell tight seal recordings, and 2) mapping receptive fields during extracellular recording and iontophoretic application of agents that open or close channels. Two different experimental paradigms will be used to accomplish the first aim. In the first, subthreshold inputs from the dorsal horn saphenous representation to the sciatic representation will be unmasked by applying lidocaine to the sciatic nerve. This design will permit analysis of intracellular responses that are synchronized with electrical stimulation of the unmasked synapses. In the second experiment, subcutaneous injections of lidocaine will be made into a neuron's receptive field while monitoring the input resistance of the neuron. These studies will provide insights into a fundamental property of nervous system function - rapid adaptation to changes in the sensory environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15NS041891-01
Application #
6357788
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Kleitman, Naomi
Project Start
2001-08-01
Project End
2005-07-31
Budget Start
2001-08-01
Budget End
2005-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$144,500
Indirect Cost
Name
University of North Texas
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Denton
State
TX
Country
United States
Zip Code
76203