Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration.
The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior.
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Related Subject Headings
- Synaptic Transmission
- Stress, Psychological
- Septal Nuclei
- Reward
- Receptors, Metabotropic Glutamate
- Receptor, Metabotropic Glutamate 5
- Receptor, Cannabinoid, CB1
- Organ Culture Techniques
- Neurology & Neurosurgery
- Mitogen-Activated Protein Kinase 3
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Synaptic Transmission
- Stress, Psychological
- Septal Nuclei
- Reward
- Receptors, Metabotropic Glutamate
- Receptor, Metabotropic Glutamate 5
- Receptor, Cannabinoid, CB1
- Organ Culture Techniques
- Neurology & Neurosurgery
- Mitogen-Activated Protein Kinase 3