Lights on Endocannabinoid-Mediated Synaptic Potentiation

Abstract

The endocannabinoid (eCB) system is a lipid-based neurotransmitter complex that plays crucial roles in the neural control of learning and memory. The current model of eCB-mediated retrograde signaling is that eCBs released from postsynaptic elements travel retrogradely to presynaptic axon terminals, where they activate cannabinoid type-1 receptors (CB 1 Rs) and ultimately decrease neurotransmitter release on a shortor long-term scale. An increasing body of evidence has enlarged this view and shows that eCBs, besides depressing synaptic transmission, are also able to increase neurotransmitter release at multiple synapses of the brain. This indicates that eCBs act as bidirectional regulators of synaptic transmission and plasticity. Recently, studies unveiled links between the expression of eCB-mediated long-term potentiation (eCB-LTP) and learning, and between its dysregulation and several pathologies. In this review article, we first distinguish the various forms of eCB-LTP based on their mechanisms, resulting from homosynaptically or heterosynaptically-mediated processes. Next, we consider the neuromodulation of eCB-LTP, its behavioral impact on learning and memory, and finally, eCB-LTP disruptions in various pathologies and its potential as a therapeutic target in disorders such as stress coping, addiction, Alzheimer's and Parkinson's disease, and pain. Cannabis is gaining popularity as a recreational substance as well as a medicine, and multiple eCB-based drugs are under development. In this context, it is critical to understand eCB-mediated signaling in its multi-faceted complexity. Indeed, the bidirectional nature of eCB-based neuromodulation may offer an important key to interpret the functions of the eCB system and how it is impacted by cannabis and other drugs.

Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles

“…[36][37][38] On the other hand, OXT-induced potentiation, while observable when combined with an electrical induction paradigm, 36,56,57 has not previously been linked to the eCB system. Even though eCB is usually associated with synaptic depression, its effects can be bi-directional depending on the concentration of eCB, the type of presynaptic neuron targeted (GABAergic versus glutamatergic), involvement of astrocytes, 58 and the precise timing of presynaptic-to-postsynaptic firing. 59 Thus, our finding of a pharmacologically induced, eCB-mediated, OXT-induced potentiation in pair-bonded females illustrates a new way for these neuromodulators to work together.…”

Spontaneous Acetylcholine Release Potentiation Induced by 2-Arachidonoylglycerol and Anandamide in Mouse Motor Synapses

“…Примеры облегчающих влияний эндоканнабиноидов на секрецию медиаторов, хотя и отмечены в литературе, но остаются немногочисленными [18,23]. Они рассматриваются сегодня как проявление значительно более широкого, чем предполагалось ранее, спектра функциональной активности эндоканнабиноидов в синапсах.…”

Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles

“…On the other hand, OXT-dependent potentiation, while observable when combined with an electrical induction paradigm (Ninan 2011; Yaseen et al 2019; Fang, Quan, and Kaba 2008), has not previously been linked to the eCB system. Interestingly, even though eCB itself is usually associated with synaptic depression, its effects can be bi-directional depending on the concentration of eCB, the type of presynaptic neuron targeted (GABAergic vs glutamatergic), the involvement of astrocytes (Piette et al 2020), and even the precise timing of presynaptic-to-postsynaptic firing (Cui, Perez, and Venance 2018). Thus, our finding of a pharmacologically induced, eCB-mediated, OXT-dependent potentiation in pair bonded females illustrates a new way for these neuromodulators to work together in the NAc.…”