Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons.

1. J Neurosci. 2004 Nov 24;24(47):10707-15.

Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated
suppression of excitation in dopamine neurons.

Melis M(1), Perra S, Muntoni AL, Pillolla G, Lutz B, Marsicano G, Di Marzo V,
Gessa GL, Pistis M.

Author information:
(1)Center of Excellence Neurobiology of Addiction, Institute of Neuroscience,
University of Cagliari, 09042 Monserrato, CA, Italy.

Endocannabinoids form a novel class of retrograde messengers that modulate short-
and long-term synaptic plasticity. Depolarization-induced suppression of
excitation (DSE) and inhibition (DSI) are the best characterized transient forms
of endocannabinoid-mediated synaptic modulation. Stimulation protocols consisting
of long-lasting voltage steps to the postsynaptic cell are routinely used to
evoke DSE-DSI. Little is known, however, about more physiological conditions
under which these molecules are released in vitro. Moreover, the occurrence in
vivo of such forms of endocannabinoid-mediated modulation is still controversial.
Here we show that physiologically relevant patterns of synaptic activity induce a
transient suppression of excitatory transmission onto dopamine neurons in vitro.
Accordingly, in vivo endocannabinoids depress the increase in firing and bursting
activity evoked in dopamine neurons by prefrontal cortex stimulation. This
phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol
(2-AG), which activates presynaptic cannabinoid type 1 receptors. 2-AG synthesis
involves activation of metabotropic glutamate receptors and Ca2+ mobilization
from intracellular stores. These findings indicate that dopamine neurons release
2-AG to shape afferent activity and ultimately their own firing pattern. This
novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear
relevance in the pathogenesis of neuropsychiatric disorders such as schizophrenia
and addiction.

DOI: 10.1523/JNEUROSCI.3502-04.2004
PMID: 15564588 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus