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Miriam Melis"Endocannabinoids in the Ventral tegmental Area: from neuromodulation to neuroprotection".

Abstract :

ndocannabinoids form a novel class of retrograde messengers that modulate short- and long-term synaptic plasticity. I will present my recent data on the physiological conditions under which these molecules are released in vitro and in vivo by dopamine cells. In fact, physiologically relevant patterns of synaptic activity induce a transient suppression of excitatory transmission onto dopamine neurons. This phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol (2-AG), which activates presynaptic CB1 receptors.

In addition, 2-AG (as well as other endocannabinoids) are released by dopamine cells following intense stimulation protocols (resembling those occurring during intense synaptic activity) and transiently suppress neurotransmitter (both glutamate and GABA) release through activation of presynaptic CB1 receptors.

As a result, I will present one (among others) condition under which these molecules are released in order to limit the synaptic drive onto VTA dopamine cells, and to prevent their pathological overexcitation. Taken together, these data indicate that dopamine neurons can release endocannabinoids to modulate (to shape afferent activity, and ultimately their own firing pattern) and protect (to limit the damage from ischemia) DA cells .

This novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear relevance in the pathogenesis of discrete disorders such as schizophrenia, Parkinson's disease and addiction. 

Selected publications

M.Melis, M. Pistis, S. Perra, A.L. Muntoni, G. Pillolla, G.L. Gessa (2004)
Endocannabinoids mediate pre-synaptic inhibition of glutamatergic transmission in rat VTA DA neurons through activation of CB1 receptors.
J Neurosci 24(1):53-62.
Melis M, Perra S, Muntoni AL, Pillolla G, Lutz B, Marsicano G, Di Marzo V, Gessa GL, Pistis M.
Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons.
J Neurosci. 2004 Nov 24;24(47):10707-15.

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