Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of the rat substantia nigra by endogenous stimulation of vanilloid receptors
J. Neurosci.. 2003-04-15; 23(8): 3136-3144
DOI: 10.1523/jneurosci.23-08-03136.2003
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1. J Neurosci. 2003 Apr 15;23(8):3136-44. doi:
10.1523/JNEUROSCI.23-08-03136.2003.
Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of
the rat substantia nigra by endogenous stimulation of vanilloid receptors.
Marinelli S(1), Di Marzo V, Berretta N, Matias I, Maccarrone M, Bernardi G,
Mercuri NB.
Author information:
(1)Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia,
University of Tor Vergata, 00179 Rome, Italy.
Growing evidence regarding the function of vanilloid receptor-1 (VR1) in the
brain suggests potential central roles of this receptor, previously described to
occur primarily in peripheral sensory neurons. In the present study, we used
electrophysiological and biochemical techniques to investigate the function and
the endogenous stimulation of VR1 in dopaminergic neurons of the substantia
nigra pars compacta (SNc). The VR1 agonist capsaicin increased the frequency of
both TTX-sensitive and -insensitive spontaneous EPSCs (sEPSCs) without affecting
their amplitude, suggesting a presynaptic site of action. In contrast, no effect
was detected with regard to GABAergic transmission. No increase in sEPSC
frequency was observed in the presence of cadmium chloride, while the
voltage-dependent calcium channel antagonist omega-conotoxin MVIIC did not
prevent capsaicin action. The VR1 antagonists capsazepine and
iodoresiniferatoxin (IRTX) blocked the effects of capsaicin. Importantly, IRTX
per se reduced sEPSC frequency, suggesting a tonic activity of VR1. The
endogenous VR1 agonist anandamide (AEA) produced an IRTX-sensitive increase in
the frequency of sEPSCs on dopaminergic neurons that was more pronounced when
protein kinase A had been activated. Furthermore, mass spectrometric analyses
and binding experiments revealed high levels of endogenous AEA and specific
binding of AEA to VR1 receptors in the SNc. These data suggest a tonic
facilitation of glutamate release exerted by VR1 in the SNc through a
stimulation of VR1 by endovanilloids, including anandamide. The increase in
sEPSC frequency by VR1 onto midbrain dopaminergic neurons suggests the
involvement of these receptors in motor and cognitive functions involving the
dopaminergic system.
DOI: 10.1523/JNEUROSCI.23-08-03136.2003
PMCID: PMC6742307
PMID: 12716921 [Indexed for MEDLINE]