Cannabinoids reveal importance of spike timing coordination in hippocampal function

Abstract

Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Delta(9)-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (<100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.

Adolescent Cannabinoid Exposure Permanently Suppresses Cortical Oscillations in Adult Mice

“…Acute cannabinoid exposure attenuates the power of neural oscillations recorded in vitro (Hajós et al, 2000(Hajós et al, , 2008 and in vivo, in freely moving animals (Robbe et al, 2006;Hajós et al, 2008;Kucewicz et al, 2011) and during working memory tasks (Kucewicz et al, 2011) by CB1R-mediated suppression of glutamate release from pyramidal neurons (Holderith et al, 2011;Sales-Carbonell et al, 2013). This CB1R-mediated attenuation of excitatory transmission preferentially suppresses the frequency and firing precision of fast-spiking GABAergic interneurons, resulting in smaller and less synchronized field potentials (Holderith et al, 2011).…”

“…Acute cannabinoid administration attenuates the power of oscillations (Hajós et al, 2000(Hajós et al, , 2008Robbe et al, 2006;Kucewicz et al, 2011) by acting at CB1Rs to suppress glutamate release from pyramidal neurons (Holderith et al, 2011;Sales-Carbonell et al, 2013). Furthermore, oscillations are suppressed in chronic marijuana users, particularly in those with an earlier age of onset of use (Skosnik et al, 2012).…”

A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

“…Hampson and Deadwyler (2000) found that D 9 -THC and WIN 55,212-2 act selectively to disrupt the encoding of events in the hippocampus during memory processing, on measuring the combined simultaneous multineuron firing rate. Recently, it was also suggested that the cannabinoids D 9 -THC and a cannabinoid CB 1 receptor agonist CP55940 disrupted the temporal coordination of hippocampal neurons, and that this effect may correlate with memory deficits in individuals (Robbe et al, 2006).…”

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making

“…The animals performed the task for 3 days without any manipulation between test days with microinjections. The dose we used falls within the dose range of previous studies employing intracerebral application of high-affinity cannabinoid agonists including ACEA and CP55940 (Fogaca et al 2012;Miller et al 1998;Moreira et al 2007;Robbe et al 2006). All microinjections were administered in a volume of 0.5 μl per side over 60 s using a stainless steel needle (30 gauge) which was directly inserted into the guide cannula, protruding 1 mm beyond the tip of the cannula.…”