Page last updated: 2024-10-24

positive regulation of long-term synaptic depression

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of long term synaptic depression. [GOC:BHF, GOC:TermGenie]

Positive regulation of long-term synaptic depression is a complex cellular process that involves a coordinated interplay of molecular mechanisms to modulate synaptic strength over extended periods. It is a fundamental aspect of neural plasticity, enabling the nervous system to adapt to changing environments and experiences. Here's a detailed breakdown of the biological process:

**1. Initiation of LTD:**

* **Induction:** LTD is typically triggered by low-frequency stimulation (LFS) of presynaptic neurons. This stimulation activates NMDA receptors, which are permeable to calcium ions.
* **Calcium Influx:** The influx of calcium through NMDA receptors triggers a cascade of intracellular signaling events.
* **Kinase Activation:** Calcium activates specific protein kinases, notably protein kinase C (PKC) and calcineurin (CaN).

**2. Molecular Mechanisms:**

* **Phosphorylation and Dephosphorylation:** PKC and CaN regulate the phosphorylation state of key proteins involved in synaptic transmission.
* **Internalization of AMPA Receptors:** One of the primary mechanisms underlying LTD is the internalization of AMPA receptors, the primary mediators of excitatory synaptic transmission. CaN-mediated dephosphorylation of AMPA receptor subunits, particularly GluA2, leads to their endocytosis.
* **Reduction of Synaptic Strength:** The removal of AMPA receptors from the postsynaptic membrane reduces the number of available receptors for neurotransmitter binding, consequently weakening the synapse.

**3. Role of Synaptic Proteins:**

* **PSD-95 and SynGAP:** LTD involves the interaction of scaffolding proteins like PSD-95 with signaling molecules like SynGAP. SynGAP is a GTPase-activating protein that inhibits Ras signaling, contributing to LTD.
* **Ubiquitin and Proteasomal Degradation:** Ubiquitination of proteins, including AMPA receptor subunits, can tag them for degradation via the proteasome pathway, further reducing their levels at the synapse.

**4. Regulation and Fine-tuning:**

* **G-Protein Coupled Receptors:** The activity of G-protein coupled receptors (GPCRs) can influence LTD. For example, activation of metabotropic glutamate receptors (mGluRs) can enhance LTD.
* **Transcriptional Regulation:** LTD can induce changes in gene expression, leading to long-lasting modifications in synaptic strength. This involves the activation of transcription factors and changes in the synthesis of proteins involved in synaptic function.

**5. Physiological Significance:**

* **Learning and Memory:** LTD is crucial for the formation and refinement of memories. It contributes to synaptic weakening, allowing for the selective strengthening of relevant connections during learning.
* **Homeostatic Plasticity:** LTD plays a role in maintaining the overall stability of neuronal networks. It counteracts excessive synaptic potentiation, preventing runaway excitation.
* **Neurological Disorders:** Disruptions in LTD mechanisms have been implicated in neurological disorders like Alzheimer's disease and schizophrenia.

**In summary,** positive regulation of long-term synaptic depression is a complex and tightly regulated process that involves a cascade of molecular events, including the activation of kinases, the internalization of AMPA receptors, and changes in gene expression. This process is fundamental to synaptic plasticity, contributing to learning, memory, and the overall stability of neural networks. '
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Proteins (2)

ProteinDefinitionTaxonomy
Potassium voltage-gated channel subfamily B member 1A voltage-gated potassium channel KCNB1 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q14721]Homo sapiens (human)
Adenylate cyclase type 8An adenylate cyclase type 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P40145]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
N-(2-aminoethyl)-5-chloro-1-naphthalenesulfonamidenaphthalenes;
sulfonic acid derivative
colforsinColforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.acetate ester;
cyclic ketone;
labdane diterpenoid;
organic heterotricyclic compound;
tertiary alpha-hydroxy ketone;
triol
adenylate cyclase agonist;
anti-HIV agent;
antihypertensive agent;
plant metabolite;
platelet aggregation inhibitor;
protein kinase A agonist
sch 23390SCH 23390 : A benzazepine that is 2,3,4,5-tetrahydro-3-benzazepine bearing a phenyl substituent at position 1, a methyl substituent at position 3, a chloro substituent at position 7 and a hydroxy substituent at position 8.

SCH 23390: a selective D1-receptor antagonist
benzazepine
sk&f-38393(R)-SKF 38393 : A 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol that is the R-enantiomer of SKF 38393.1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol