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Seizures down-regulate muscarinic cholinergic receptors in hippocampal formation
Abstract:
Muscarinic cholinergic receptors (MCR) have been previously shown to decline in the hippocampal formation (HPF) of amygdala-kindled rats. Seizures have been proposed as the process responsible for this down-regulation. We now demonstrate similar down-regulation of MCR within HPF in 3 additional methods of inducing seizures: electroconvulsive shock, entorhinal kindling and entorhinal lesion. Two key parameters which causally link the MCR declines with seizures are their time course and reversal with anticonvulsants. The transient decline of MCR induced by entorhinal lesion-induced seizures parallels the time course established in amygdala kindling. Further, phenobarbital could block both these seizures and the MCR declines. Together, this supports the relationship of seizures causing the declines. We postulate that the MCR down-regulation represents an endogenous inhibitory response of neurons that are intensely and repeatedly depolarized during the seizures.
Insights
Seizures down-regulate muscarinic cholinergic receptors (MCR) in the hippocampus. This decline is linked to seizure activity and reversed by anticonvulsants, suggesting an endogenous neuronal response.
Area of Science:
- Neuroscience
- Neuropharmacology
- Cellular Neuroscience
Background:
- Muscarinic cholinergic receptors (MCR) expression decreases in the hippocampus of amygdala-kindled rats.
- Seizures are hypothesized to cause this MCR down-regulation.
Purpose of the Study:
- To investigate if MCR down-regulation in the hippocampus is a general effect of seizures.
- To establish the causal link between MCR decline and seizure activity.
Main Methods:
- Inducing seizures through electroconvulsive shock, entorhinal kindling, and entorhinal lesions in rats.
- Analyzing MCR levels in the hippocampal formation (HPF).
- Examining the time course of MCR decline and its reversal with phenobarbital.
Main Results:
- MCR down-regulation was observed in the HPF across three additional seizure induction methods.
- The time course of MCR decline following entorhinal lesion-induced seizures mirrored that of amygdala kindling.
- Phenobarbital administration prevented both seizures and MCR down-regulation.
Conclusions:
- Seizure activity causally leads to MCR down-regulation in the hippocampus.
- This down-regulation may serve as an endogenous inhibitory mechanism for neurons experiencing intense depolarization during seizures.