Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Abstract

Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABA B synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.

Alterations to pre-pulse inhibition (PPI) in chronic cannabis users are secondary to sustained attention deficits

“…Such a contention could explain the lack of significant differences between controls and cannabis users in the study by Quednow et al (2004) which used an uninstructed PPI task. A number of recent studies have shown that sensory gating of the P50 response (a psychophysiological measure that has been likened to PPI) is disrupted by administration of cannabinoids in humans (Rentzch et al 2007) and in rats (Hajos et al 2008;Zachariou et al 2008), suggesting that cannabinoids disrupt early information processing or gating. However, drug conditions may have differing effects on PPI and P50 gating (e.g.…”

Large-scale neural dynamics: Simple and complex

“…There are a number of natural extensions to neural field models to incorporate ever more biological realism, including the incorporation of slow intrinsic currents that underlie bursting behaviour in single neurons [86,11], synaptic depression and adaptation [87], dendritic processing [61], neuromodulation, say by endo-cannabinoids [88], and anaesthetic drug action [66,89,68,90]. Moreover, it is possible to gener-alise such models even further to treat feature selectivity such as that observed in visual cortex for orientation [10], spatial frequency [91] and texture [92].…”

Role of cannabis and endocannabinoids in the genesis of schizophrenia

“…This wave, known as N40, is considered a homolog to the P50 wave recorded in humans (Adler et al 1986). The cannabinoid agonist WIN55,212-2 disrupts auditory gating in rats, in the hippocampus (CA3, dentate gyrus) and the medial prefrontal cortex (mPFC), and this disruption is prevented by the CB 1 antagonist SR141716A Zachariou et al 2008). The CB 1 agonist CP-55940 has been reported not only to impair PPI in rats but also auditory gating and neuronal synchrony in limbic areas such as the hippocampus and entorhinal cortex, as evaluated through theta field potential oscillations (Hajós et al 2008).…”