ANATOMY AND PHYSIOLOGY OF SUBSTANTIA NIGRA AFFERENTS

Project Details

Description

DESCRIPTION: (Adapted from the applicant's abstract) The experiments in
this proposal are designed to describe the anatomy and physiology of
afferents that control the activity of substantia nigra dopamine neurons.
In particular, various aspects of a GABAergic pathway to dopaminergic
neurons originating from the axon collaterals of non-dopaminergic substantia
nigra pars reticulata projection neurons will be studied. The central
hypothesis is that many of the important inputs to dopaminergic neurons that
control the rate of firing and spontaneous activity are filtered through
pars reticulata neurons. Six specific aims are proposed. Aim 1. To test
the hypothesis that there is a physiologically functional monosynaptic
connection between substantia nigra pars reticulata GABAergic projections
neurons and pars compacta nigrostriatal dopaminergic neurons with
electrophysiological means. Aim 2. To determine the subtype of the GABA
receptor on the dopaminergic nigrostriatal neuron that mediates the
inhibitory influence of GABAergic afferents arising from neostriatum, globus
pallidus and substantia nigra par reticulata with in vivo
neuropharmacological studies. Aim 3. To determine the relative influences
of GABA-A and GABA-B synaptic inputs on the firing pattern of nigrostriatal
neurons in vivo. Aim 4. To look for anatomical evidence of a direct
monosynaptic connection between substantia nigra pars reticulata projection
neurons and nigrostriatal dopaminergic neurons by light and electron
microscopic analysis of the axon collaterals of electrophysiologically
characterized pars reticulata neurons that were intracellularly or
juxtacellularly labeled with biocytin. Aim 5. To test the hypothesis that
activation of GABAergic pars reticulata neuron axon collaterals and/or
pallidonigral inputs are responsible for the inhibitory responses seen in
pars compacta dopaminergic neurons after stimulation of presumed excitatory
inputs. Aim 6. To test the hypothesis that individual striatonigral and
pallidonigral afferents synapse with either dopaminergic or non-dopaminergic
neurons in substantia nigra by intracellular or juxtacellular labeling and
tracing axons to nigra and performing double label electron microscopy.
StatusActive
Effective start/end date2/1/976/30/21

Funding

  • National Institute of Neurological Disorders and Stroke: $331,209.00
  • National Institute of Neurological Disorders and Stroke: $334,590.00
  • National Institute of Neurological Disorders and Stroke: $546,055.00
  • National Institute of Neurological Disorders and Stroke: $98,324.00
  • National Institute of Neurological Disorders and Stroke: $50,000.00
  • National Institute of Neurological Disorders and Stroke: $540,738.00
  • National Institute of Neurological Disorders and Stroke: $601,212.00
  • National Institute of Neurological Disorders and Stroke: $337,969.00
  • National Institute of Neurological Disorders and Stroke: $386,250.00
  • National Institute of Neurological Disorders and Stroke: $63,500.00
  • National Institute of Neurological Disorders and Stroke: $331,209.00
  • National Institute of Neurological Disorders and Stroke: $581,751.00
  • National Institute of Neurological Disorders and Stroke: $525,950.00

ASJC

  • Medicine(all)
  • Neuroscience(all)
  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physiology
  • Oncology
  • Cancer Research
  • Anatomy

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