Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy.

Abstract

Perisomatic inhibition from basket cells plays an important role in regulating pyramidal cell output. Two major subclasses of CA1 basket cells can be identified based on their expression of either cholecystokinin (CCK) or parvalbumin. This study examined their fates in the mouse pilocarpine model of temporal lobe epilepsy. Overall, immunohistochemical labeling of GABAergic boutons in the pyramidal cell layer of CA1 was preserved in the mouse model. However, CCK-labeled boutons in this layer were chronically reduced, whereas parvalbumin-containing boutons were conserved. Immunohistochemistry for cannabinoid receptor 1 (CB(1)), another marker for CCK-containing basket cells, also labeled fewer boutons in pilocarpine-treated mice. Hours after status epilepticus, electron microscopy revealed dark degenerating terminals in the pyramidal cell layer with lingering CCK and CB(1) immunoreactivity. In mice with recurrent seizures, carbachol-induced enhancement of spontaneous IPSCs (sIPSCs) originating from CCK-containing basket cells was accordingly reduced in CA1 pyramidal cells. By suppressing sIPSCs from CCK-expressing basket cells, a CB(1) agonist reverted the stimulatory effects of carbachol in naive mice to levels comparable with those observed in cells from epileptic mice. The agatoxin-sensitive component of CA1 pyramidal cell sIPSCs from parvalbumin-containing interneurons was increased in pilocarpine-treated mice, and miniature IPSCs were reduced, paralleling the decrease in CCK-labeled terminals. Altogether, the findings are consistent with selective reduction in perisomatic CA1 pyramidal cell innervation from CCK-expressing basket cells in mice with spontaneous seizures and a greater reliance on persisting parvalbumin innervation. This differential alteration in inhibition may contribute to the vulnerability of the network to seizure activity.

• Authors: Megan S Wyeth, Nianhui Zhang, Istvan Mody, Carolyn R Houser
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 30 Issue 26 Pg. 8993-9006 (Jun 30 2010) ISSN: 1529-2401 [Electronic] United States
• PMID: 20592220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Parvalbumins
• Receptor, Cannabinoid, CB1
• Pilocarpine
• gamma-Aminobutyric Acid
• Cholecystokinin

Topics

• Animals
• CA1 Region, Hippocampal (drug effects, physiopathology, ultrastructure)
• Cholecystokinin (metabolism)
• Disease Models, Animal
• Epilepsy, Temporal Lobe (chemically induced, pathology, physiopathology)
• Inhibitory Postsynaptic Potentials (drug effects)
• Male
• Mice
• Neural Pathways (drug effects, physiopathology, ultrastructure)
• Neurons (drug effects, physiology, ultrastructure)
• Parvalbumins (metabolism)
• Pilocarpine
• Presynaptic Terminals (drug effects, physiology, ultrastructure)
• Pyramidal Cells (drug effects, physiopathology, ultrastructure)
• Receptor, Cannabinoid, CB1 (agonists, metabolism)
• Status Epilepticus (chemically induced, pathology, physiopathology)
• gamma-Aminobutyric Acid (metabolism)