Endocannabinoids Modulate Olfactory System Development and Function

The endocannabinoid system is expressed in brain centers involved in a wide variety of functions which makes it an ideal target for disease therapy and prevention. Unlike major excitatory and inhibitory neurotransmitters such as glutamate and GABA, en-dogenously produced cannabinoids have been shown to play a complimentary role as neuromodulators by acting as gain regulators of neural signals. The endocannabinoid system consists of cannabinoid receptors, CB1R and CB2R, and endogenously generat-ed lipid-based neurotransmitters, 2-AG (2-arachidonoylglycerol) and anandamide, the endocannabinoids. In the central nervous system, these signaling molecules are re-leased from postsynaptic cells in an on-demand manner. This retrograde transmission from post- to presynaptic neurons and the binding of endocannabinoids onto the pre-synaptic CB1 receptors modulates the magnitude of release of glutamate and GABA, either enhanced or inhibited, depending on the brain area under study. Research has focused on the role of the endocannabinoid system in the limbic system such as the hippocampus and amygdala. Research is increasing regarding the role that endocan-nabinoids play in other brain centers such as the olfactory system with particular em-phasis on the role of the endocannabinoid system in neural networks of the main ol-factory bulb. This review aims to bring together research within the overlap of the ol-factory system and the endocannabinoid system. By better understanding the unique neuromodulator and neurodevelopmental role of endocannabinoids in the brain, in-sight into understanding how to mitigate disease states that result from aberrant re-lease of glutamate and GABA such as stroke, epilepsy, and schizophrenia is expected to be gained.