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Updated: Jun 1, 2026
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Assessment of Long-term Depression Induction in Adult Cerebellar Slices
Published on: October 16, 2019
Serotonin induces long-term depression at corticostriatal synapses
Brian N Mathur1, Nicole A Capik, Veronica A Alvarez
1Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20852-9411, USA.
Summary
Serotonin (5-HT) activates 5-HT(1b) receptors, causing long-term depression (LTD) in corticostriatal circuits. This 5-HT-LTD interacts with dopamine-dependent LTD, influencing action learning and brain disorders.
Area of Science:
- Neuroscience
- Neuropharmacology
- Molecular Biology
Background:
- The striatum is crucial for motor control and action learning.
- It receives significant monoaminergic inputs, including serotonin.
- Understanding neuromodulation is key to deciphering striatal function.
Purpose of the Study:
- To investigate serotonergic modulation of corticostriatal neurotransmission in rats and mice.
- To characterize the novel form of long-term depression (LTD) induced by serotonin (5-HT).
- To explore the interaction between serotonergic and dopaminergic LTD in the striatum.
Main Methods:
- Electrophysiological recordings in rodent corticostriatal slices.
- Pharmacological manipulation using selective serotonin reuptake inhibitors (SSRIs).
- Investigating intracellular signaling pathways, specifically the cAMP pathway.
Main Results:
- Serotonin (5-HT) activates 5-HT(1b) receptors, inducing a presynaptically mediated LTD of glutamate release (5-HT-LTD).
- This 5-HT-LTD is dependent on the cAMP pathway and can be induced by endogenous 5-HT.
- 5-HT-LTD is mutually occlusive with dopamine/endocannabinoid-dependent LTD, indicating a shared presynaptic mechanism.
Conclusions:
- Serotonergic and dopaminergic systems interact to persistently modify corticostriatal circuits.
- These interactions may play a significant role in action learning processes.
- Dysregulation of these interacting pathways could contribute to striatal-based neurological and psychiatric disorders.
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