Endocannabinoid‐mediated neuromodulation in the main olfactory bulb at the interface of environmental stimuli and central neural processing

Abstract

The olfactory system has become an important functional gateway to understand and analyze neuromodulation since olfactory dysfunction and deficits have emerged as prodromal and, at other times, as first symptoms of many of neurodegenerative, neuropsychiatric and communication disorders. Considering olfactory dysfunction as outcome of altered, damaged and/or inefficient olfactory processing, in the current review, we analyze how olfactory processing interacts with the endocannabinoid signaling system. In the human body, endocannabinoid synthesis is a natural and on‐demand response to a wide range of physiological and environmental stimuli. Our current understanding of the response dynamics of the endocannabinoid system is based in large part on research advances in limbic system areas, such as the hippocampus and the amygdala. Functional interactions of this signaling system with olfactory processing and associated pathways are just emerging but appear to grow rapidly with multidimensional approaches. Recent work analyzing the crystal structure of endocannabinoid receptors bound to their agonists in a signaling complex has opened avenues for developing specific therapeutic drugs that could help with neuroinflammation, neurodegeneration, and alleviation/reduction of pain. We discuss the role of endocannabinoids as signaling molecules in the olfactory system and the relevance of the endocannabinoid system for synaptic plasticity.

Chemosensory Ability and Sensitivity in Health and Disease: Epigenetic Regulation and COVID-19

“…Our review of the published literature and analysis of the interactions of environmental factors with the chemical senses indicate a higher degree of vulnerability for these senses as a function of diverse effects of living conditions, including altered histopathology due to bacterial and viral infections. In day-to-day living, exposure to odorants imparts a significant impact on the autonomic nervous system with a decline in olfactory processing, perception of stress, and its resulting physiological outcomes [ 85 , 86 , 106 , 107 ]. Indeed, odorants come under the category of strong environmental stimuli, specifically in humans; and the sense of olfaction has a crucial impact on overall behavior, including feeding [ 108 ].…”

Special issue editorial: Cannabinoid signalling in the brain: New vistas

“…Another important brain region where CB1 receptors have been involved in the regulation of synaptic events is the olfactory bulb (Soria‐Gomez et al, 2014). In this regard, Heinbockel et al (2021) nicely review the role of endocannabinoids as signalling molecules in the olfactory system and the relevance of CB1 receptors for synaptic plasticity in this particular brain region.…”

Cannabinoids Regulate Sensory Processing in Early Olfactory and Visual Neural Circuits

“…While the basic signaling functions of the endocannabinoid system are understood relatively well in limbic structures such as the hippocampus and the amygdala, this signaling system is less well understood in the olfactory pathway (Terral et al, 2020;Heinbockel et al, 2021) and visual system. Here, we describe the early olfactory and visual pathways and compare and contrast endocannabinoids as signaling molecules in them and the relevance of the endocannabinoid system for synaptic plasticity.…”