Cannabinoids alter spontaneous firing, bursting, and cell synchrony of hippocampal principal cells

Anushka V. Goonawardena, Gernot Riedel, Robert E. Hampson*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Both natural and synthetic cannabinoid receptor (e. g., CB1) agonists such as Delta(9)-THC, WIN 55,212-2 (WIN-2), and HU-210 disrupt spatial cognition presumably through the inhibition of synchrony of hippocampal ensemble firing to task-related events. Although the CB1 receptor agonist CP 55,940 also disrupts the synchronous firing of hippocampal neurons, it does not seem to affect the average firing rate. This difference is not readily explained by the chemical structure and pharmacology of the different compounds thus warranting a more detailed examination into (i) how other cannabinoids affect the spontaneous firing, bursting, and cell synchrony of hippocampal principal cells located in CA3 and CA1 subfields, and (ii) whether these effects are indeed mediated through CB1 receptors, which will be explored by the selective antagonist AM-251. Male Long-Evans rats surgically implanted with multielectrode arrays to hippocampal CA3 and CA1 were anesthetized and principal cells discharging at 0.25-6.0 Hz were isolated and "tracked'' following the systemic administration of Tween-80, Delta(9)-THC (1 or 3 mg/kg) or WIN-2 (1 mg/kg) or HU-210 (100 mu g/kg), and 1.5 mg/kg AM-281. All cannabinoids except for 1 mg/kg Delta(9)-THC reliably reduced average firing rates and altered "burst" characteristics, which were reversible with AM-281 for Delta(9)-THC and WIN-2 but not for HU-210. In addition, all cannabinoids disrupted intrasubfield and intersubfield ensemble synchrony of pyramidal cells, which is an effect insensitive to AM-281 and thus unlikely to be CB1 mediated. We consider these cannabinoid effects on spike timing and firing/bursting of principal hippocampal neurons carried by CB1 and non-CB1 receptors to be physiological underpinnings of the cognitive impairments inherent to cannabinoid exposure. (C) 2010 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)520-531
Number of pages12
JournalHippocampus
Volume21
Issue number5
Early online date25 Jan 2010
DOIs
Publication statusPublished - May 2011

Keywords

  • entorhinal cortex
  • pyramidal cells
  • rat-brain slices
  • prefrontal cortex
  • CB1 receptors
  • theta-oscillations
  • rat
  • acetylcholine-release
  • firing rate
  • impairs spatial memory
  • receptor agonist
  • cannabinoid
  • synchrony
  • glutamatergic synaptic-transmission
  • hippocampus
  • bursting
  • single unit

Cite this