Cannabinoid signaling and risk in Huntington’s disease

Published on September 2, 2022

Imagine your body is a circuit board, and every connection needs to be regulated to function properly. In Huntington’s disease (HD), there’s a disruption in the communication system due to dysregulated endocannabinoid (eCB) signaling and the loss of cannabinoid receptors. Scientists have created a computational model to understand this phenomenon better. It turns out that eCB signaling acts like a powerful homeostatic control mechanism, keeping excess glutamate in check. Excess glutamate, a molecule responsible for transmitting brain signals, poses a metabolic risk in HD. This risk increases when certain factors like cortico-striatal long-term depression (LTD) and increased cortical-striatal activity are present. The model also mimics the progressive loss of cannabinoid receptors on inhibitory terminals as the excitatory/inhibitory ratio changes. These findings provide valuable insights into HD and how cannabinoids play a crucial role in maintaining neural balance. To delve deeper into this fascinating research, check out the full article!

Dysregulated endocannabinoid (eCB) signaling and the loss of cannabinoid receptors (CB1Rs) 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.

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