The CB2 receptor is part of the endocannabinoid system (ECS). This family of receptors and signaling substances exists in many organisms including humans. It is a biochemical control system which is involved in the regulation of numerous physiological processes. Its name refers to the fact that chemicals derived from the cannabis plant bind to receptors of the ECS. So far, there are two known types of these receptors: The CB2 receptor has no psychoactive effect. Hence, the mind-altering effects triggered by the consumption of cannabis are ascribed to the "cannabinoid type 1 receptor".

 "Until now, this receptor was considered part of the immune system without function in nerve cells. However, our study shows that it also plays an important role in the signal processing of the brain," explains senior author of the study published in the journal Neuron.

As the researchers demonstrated in an animal model, the CB2 receptor raises the excitation threshold of nerve cells in the hippocampus. They found that action potential-driven (endocannabinoids) eCB release leads to a long-lasting membrane potential hyperpolarization in hippocampal principal cells that is independent of CB₁Rs.

The hyperpolarization, which is specific to CA3 and CA2 pyramidal cells (PCs), depends on the activation of neuronal CB₂Rs, as shown by a combined pharmacogenetic and immune-histochemical approach. Upon activation, they modulate the activity of the sodium-bicarbonate co-transporter, leading to a hyperpolarization of the neuron. CB₂R activation occurred in a purely self-regulatory manner, robustly altered the input/output function of CA3 PCs, and modulated gamma oscillations in vivo. 

The results of the current study could contribute to a better understanding of disease mechanisms and provide a starting point for novel medications. "Brain activity is disturbed in schizophrenia, depression, Alzheimer's disease and other neuropsychiatric disorders. Pharmaceuticals that bind to the CB2 receptor could possibly influence the activity of brain cells and thus become part of a therapy," author concludes.

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