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cGMP-induced presynaptic depression and postsynaptic facilitation at glutamatergic synapses in visual cortex
Ji Ye Wei1, Xiaotao Jin, Ethan D Cohen
1Department of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, P.O. Box 208061, New Haven, CT 06520-8061, USA.
Brain Research
|January 30, 2002
Summary
Cyclic GMP (cGMP) rapidly and reversibly alters synaptic transmission in the visual cortex via cGMP-dependent protein kinase (PKG). It depresses presynaptic function while enhancing postsynaptic NMDA receptor activity, impacting neuronal plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- The role of cyclic GMP (cGMP) in modulating synaptic efficacy is not well understood.
- cGMP is a crucial intracellular messenger involved in various cellular processes.
Purpose of the Study:
- To investigate the rapid and reversible effects of cGMP on synaptic transmission in the rodent visual cortex.
- To elucidate the mechanisms by which cGMP influences excitatory synaptic function.
Main Methods:
- Electrophysiological recordings (EPSPs, EPSCs, calcium currents) in visual cortex slices and cultures.
- Application of cGMP analogs (8-Br-cGMP) and PKG activators (Sp-8-Br-PET-cGMPS).
- Use of PKG-specific inhibitory peptides to determine presynaptic versus postsynaptic actions.
Main Results:
- cGMP analogs reduced stimulus-evoked EPSPs and spontaneous EPSC frequency, indicating presynaptic inhibition.
- Presynaptic inhibition was confirmed by PKG inhibitory peptides.
- cGMP enhanced NMDA receptor responses postsynaptically, but not AMPA/kainate responses.
- Whole-cell calcium currents were reduced by cGMP analogs.
Conclusions:
- cGMP, acting via PKG, exerts dual presynaptic (depressive) and postsynaptic (facilitatory) effects on excitatory synapses in the visual cortex.
- These opposing actions may regulate synaptic input balance, promoting synaptic facilitation and neuronal plasticity.
- The findings provide new insights into the complex roles of cGMP in cortical circuit function.