CCK-8S increases the firing frequency of CCK-positive neurons and facilitates excitatory synaptic transmission in primary rat hippocampal neurons

Neurosci Lett. 2013 Aug 9:549:34-9. doi: 10.1016/j.neulet.2013.06.043. Epub 2013 Jul 1.

Abstract

The neuropeptide cholecystokinin octapeptide (CCK) is involved in a variety of brain functions. In the hippocampus, most CCK is released from CCK-positive (CCK+) neurons, but the effects of CCK on CCK+ neurons are poorly understood. We employed primary hippocampal cultures to explore the modulatory effect of CCK on CCK+ neurons. CCK-8S (0.2 μM) was added to the culture medium from day in vitro 2 (DIV-2) to DIV-11. An adenovirus integrated with the CCK promoter was used to label CCK+ neurons. Whole-cell patch clamp recording was carried on to record the electrophysiology properties. The results show that: (1) CCK-8S significantly decreased membrane capacity but increased the membrane resistance (Rm) of CCK+ neurons, (2) CCK-8S increased action potential (AP) firing frequency of CCK+ neurons but did not affect the firing pattern, (3) CCK-8S facilitated CCK+ neuron excitatory synaptic transmission but attenuated inhibitory synaptic transmission, and (4) the expression of postsynaptic density-95 (PSD-95) in cultured hippocampal neurons was elevated by CCK-8S treatment. Our results demonstrate that CCK-8S significantly alters the membrane electrophysiological characteristics and synaptic activity of cultured hippocampal CCK+ neurons. These findings may enhance our understanding of the modulatory effect of CCK in the brain.

Keywords: CCK-positive neuron; Cholecystokinin; Hippocampus; Interneuron; Whole-cell patch clamp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / drug effects*
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Sincalide / analogs & derivatives*
  • Sincalide / pharmacology

Substances

  • 8-sulfocholecystokinin octapeptide
  • Sincalide