Effects of Δ9-Tetrahydrocannabinol on Human Working Memory Function

Bossong, Matthijs G.; Jansma, J.; Hell, H.H. van; Jager, Gerry; Oudman, Erik; Saliasi, Emi; Kahn, René S.; Ramsey, Nick F.

doi:10.1016/j.biopsych.2012.01.008

Cited by 81 publications

(55 citation statements)

References 51 publications

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“…Probable sites for the amnestic effect of cannabis are the hippocampus and the prefrontal cortex (Bhattacharyya et al 2009;Bossong et al 2012), structures which are highly involved in various forms of learning and memory. Large amounts of cannabinoid receptors (CB1) and anandamide, the endogenous cannabinoid, have been found in the hippocampus and the prefrontal cortex, suggesting a functional role of CB1 receptors in learning and memory (Davies et al 2002;Egerton et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

et al. 2014

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Section: Introductionmentioning

confidence: 99%

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

et al. 2014

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“…Here we specifically addressed this issue by comparing the impact of systemic and local injections of the CB1R agonist CP55940 on cortical network oscillations recorded from freely moving mice lacking CB1R expression in distinct neuronal populations. The results reveal the cell-and region-specific mechanisms underlying a dual modulation of cortical synchrony by exogenous cannabinoids and pave the way to a refined understanding of the cognitive alterations associated with marijuana consumption (21,22). …”

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confidence: 99%

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

Sales-Carbonell

Rueda-Orozco

Soria-Gómez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region-and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory "high" experienced during recreational consumption of marijuana.annabinoids are a family of compounds that activate cannabinoid receptors, which are well known for their psychotropic effects and therapeutic potentials. The type 1 cannabinoid receptor (CB1R) is massively expressed in the brain at the synaptic terminals of excitatory and inhibitory neurons, and its activation by exogenous or endogenous cannabinoids decreases neurotransmitter release (1-3). One largely unanswered question is how the elementary decreases in excitatory and inhibitory synaptic transmissions induced by systemic intake of cannabinoids interact to produce alterations in neuronal network activity in vivo. A number of recent studies combining systemic injections of CB1R agonists and antagonists with electrophysiological recordings in the hippocampus and neocortex of awake or anesthetized rodents have shown that a hallmark of cannabinoids effects on neuronal network activity is a decrease in synchrony (4-9). Specifically, systemic CB1R activation has been shown to decrease (i) the amplitude of the hippocampal θ rhythm (4, 7, 8), (ii) the amplitude of γ oscillations in the hippocampus (4, 7, 10), enthorinal cortex (8), and prefrontal cortex (7), (iii) the incidence of hippocampal ripples (4, 6, 11), and (iv) spiking correlation in the hippocampus and prefrontal cortex (4,5,7,9).In contrast to the consistent reports that cannabinoids dampen cortical network oscillations, other findings suggest that they could also increase synchrony. First, CB1R are predominantly expressed by GABAergic forebrain neurons (12), and their activation leads to decreased GABA ...

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“…Theta phase-locking correlates with successful DNMS performance (Hyman et al, 2010, 2011), and in similar spatial working memory tasks, cannabinoid agonists impaired theta phase-locking of medial prefrontal cortical neurons to hippocampal LFP (Kucewicz et al, 2011), decreased theta power, and reduced temporal coordination of hippocampal principal cell ensembles (Robbe et al, 2006). In humans, THC reduces EEG theta power and synchrony (Ilan et al, 2005), working memory speed (Böcker et al, 2010), accuracy, (Ilan et al, 2004), and activation of the working memory network (Bossong et al, 2012). Interesting, it was shown that decreased frontal theta power correlates with increased default mode network (DMN) activity (Scheeringa et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Multifractal analysis of information processing in hippocampal neural ensembles during working memory under Δ9-tetrahydrocannabinol administration

Fetterhoff

Opriş

Simpson

et al. 2015

Journal of Neuroscience Methods

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Background Multifractal analysis quantifies the time-scale-invariant properties in data by describing the structure of variability over time. By applying this analysis to hippocampal interspike interval sequences recorded during performance of a working memory task, a measure of long-range temporal correlations and multifractal dynamics can reveal single neuron correlates of information processing. New method Wavelet leaders-based multifractal analysis (WLMA) was applied to hippocampal interspike intervals recorded during a working memory task. WLMA can be used to identify neurons likely to exhibit information processing relevant to operation of brain–computer interfaces and nonlinear neuronal models. Results Neurons involved in memory processing (“Functional Cell Types” or FCTs) showed a greater degree of multifractal firing properties than neurons without task-relevant firing characteristics. In addition, previously unidentified FCTs were revealed because multifractal analysis suggested further functional classification. The cannabinoid-type 1 receptor partial agonist, tetrahydrocannabinol (THC), selectively reduced multifractal dynamics in FCT neurons compared to non-FCT neurons. Comparison with existing methods WLMA is an objective tool for quantifying the memory-correlated complexity represented by FCTs that reveals additional information compared to classification of FCTs using traditional z-scores to identify neuronal correlates of behavioral events. Conclusion z-Score-based FCT classification provides limited information about the dynamical range of neuronal activity characterized by WLMA. Increased complexity, as measured with multifractal analysis, may be a marker of functional involvement in memory processing. The level of multifractal attributes can be used to differentially emphasize neural signals to improve computational models and algorithms underlying brain–computer interfaces.

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Effects of Δ9-Tetrahydrocannabinol on Human Working Memory Function

Cited by 81 publications

References 51 publications

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

Multifractal analysis of information processing in hippocampal neural ensembles during working memory under Δ9-tetrahydrocannabinol administration

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