AUTHOR=Humble James , Kozloski James R. 

TITLE=Cannabinoid signaling and risk in Huntington's disease

JOURNAL=Frontiers in Computational Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2022.903947

DOI=10.3389/fncom.2022.903947

ISSN=1662-5188

ABSTRACT=<p>Dysregulated endocannabinoid (eCB) signaling and the loss of cannabinoid receptors (<italic>CB</italic>1<italic>R</italic>s) are important phenotypes of Huntington's disease (HD) but the precise contribution that eCB signaling has at the circuit level is unknown. Using a computational model of spiking neurons, synapses, and eCB signaling, we demonstrate that eCB signaling functions as a homeostatic control mechanism, minimizing excess glutamate. Furthermore, our model demonstrates that metabolic risk, quantified by excess glutamate, increases with cortico-striatal long-term depression (LTD) and/or increased cortico-striatal activity, and replicates a progressive loss of cannabinoid receptors on inhibitory terminals as a function of the excitatory/inhibitory ratio.</p>