retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission

Definition

Target type: biologicalprocess

Modulation of synaptic transmission by cell-cell signaling from postsynapse to presynapse, across the synaptic cleft, mediated by nitric oxide. [GOC:dos]

Retrograde trans-synaptic signaling by nitric oxide (NO) is a crucial mechanism modulating synaptic transmission, influencing neuronal plasticity and communication. This process involves the release of NO from the postsynaptic neuron in response to neuronal activity, diffusing across the synaptic cleft and activating signaling pathways in the presynaptic neuron.

Here's a detailed breakdown of the process:

1. **Postsynaptic Activation:** When a postsynaptic neuron is activated, elevated intracellular calcium levels trigger the activation of the enzyme nitric oxide synthase (NOS). NOS converts L-arginine into NO, a highly diffusible gaseous molecule.

2. **NO Diffusion:** NO readily diffuses across the synaptic cleft, a narrow space separating the presynaptic and postsynaptic neurons. This rapid diffusion allows NO to reach the presynaptic terminal.

3. **Presynaptic Targets:** Within the presynaptic terminal, NO interacts with several signaling molecules, including soluble guanylate cyclase (sGC), a key enzyme in cGMP signaling. NO binds to and activates sGC, leading to the production of cyclic GMP (cGMP), a second messenger molecule.

4. **cGMP-mediated Effects:** cGMP acts as a signaling molecule within the presynaptic terminal, modulating several key processes related to synaptic transmission. These include:
* **Presynaptic Neurotransmitter Release:** cGMP can influence the release of neurotransmitters by modulating the activity of voltage-gated calcium channels, which control the influx of calcium ions that trigger exocytosis.
* **Synaptic Plasticity:** cGMP plays a role in long-term potentiation (LTP), a mechanism underlying learning and memory. LTP involves persistent strengthening of synaptic connections, and NO-mediated cGMP signaling is thought to contribute to this process.
* **Synaptic Depression:** In some cases, NO signaling can lead to synaptic depression, a decrease in synaptic strength. This is often associated with prolonged or excessive neuronal activity.

5. **Negative Feedback Loop:** The retrograde signaling of NO can also act as a negative feedback loop, regulating the postsynaptic neuron's activity. NO can inhibit the activity of NMDA receptors, glutamate receptors that are crucial for synaptic plasticity.

**Overall, retrograde trans-synaptic signaling by NO is a dynamic and complex process with multifaceted effects on synaptic transmission. It contributes to neuronal plasticity, learning, and memory, and plays a crucial role in fine-tuning neuronal communication.**
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Compounds (5)