Project: Research project

Project Details


Cyclic GMP is an important second messenger in many tissues including the
Central Nervous System. It is the central hypothesis of this proposal
that cGMP plays an important role in regulating synaptic efficacy in the
developing and mature mammalian visual system and that the actions of
cGMP are mediated both by a class of cyclic nucleotide gated cation
channels and by cGMP-dependent protein kinases.

The overall hypothesis of this proposal will be tested with three
specific aims. In the first, the levels of expression and cellular
distribution of molecules involved in both cGMP metabolism and cGMP
actions will be measured during normal development and in dark-reared
animals. The results of these experiments will indicate whether cGMP acts
in the same way in all cortical neurons, whether cGMP is used as a
messenger at all stages of development and whether patterned visual input
alters the cGMP second messenger system.

The second specific aim will determine whether cGMP levels in visual
cortex are regulated by neural activity by measuring the concentrations
of cGMP in cortical slices following treatment with selected
neurotransmitter agonists and antagonists. These experiments will focus
on glutamate, acetylcholine and noradrenaline because these have been
implicated in the regulation of cGMP levels and in visual cortical

The third specific aim will test directly whether cGMP can modulate
membrane properties and synaptic interactions of identified visual
cortical neurons. Direct and indirect effects of cGMP on membrane
conductances will be measured by recording from cells identified by
retrograde transport or antibody labeling. The effects of cGMP on
responses to glutamate receptor agonists will be measured to determine
whether receptor sensitivity or desensitization is altered. Finally, the
ability of cGMP to alter synaptic interactions between cortical neurons
will be measured. Using a series of agonists and antagonists selective
for cGMP-dependent protein kinases of cyclic nucleotide gated cation
channels, experiments will be carried out to determine the pathway by
which cGMP exerts its effects.

Overall, this project will elucidate the functions of an important second
messenger system in visual cortex, particularly the ways in which cGMP
can alter the efficacy of synaptic interactions between cortical neurons.
The information gained from these experiments will improve understanding
of normal information processing and of important developmental
abnormalities that affect visual cortex such as amblyopia and strabismus.
Effective start/end date3/1/973/31/05


  • National Eye Institute: $367,875.00
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute: $367,875.00
  • National Eye Institute: $408,750.00
  • National Eye Institute: $367,875.00
  • National Eye Institute
  • National Eye Institute: $263,350.00


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