GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

Leire Reguero, Nagore Puente, Izaskun Elezgarai, Juan Mendizabal-Zubiaga, Miren Josune Canduela, Ianire Buceta, Almudena Ramos, Juan Suárez, Fernando Rodríguez de Fonseca, Giovanni Marsicano, Pedro Grandes
PLoS ONE. 2011-10-11; 6(10): e26167
DOI: 10.1371/journal.pone.0026167

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1. PLoS One. 2011;6(10):e26167. doi: 10.1371/journal.pone.0026167. Epub 2011 Oct 11.

GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1
cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

Reguero L(1), Puente N, Elezgarai I, Mendizabal-Zubiaga J, Canduela MJ, Buceta I,
Ramos A, Suárez J, Rodríguez de Fonseca F, Marsicano G, Grandes P.

Author information:
(1)Department of Neurosciences, Faculty of Medicine and Dentistry, Basque Country
University, Leioa, Spain.

BACKGROUND: Type-1 cannabinoid receptors (CB(1)R) are enriched in the
hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that
participates in homeostatic and behavioral functions including food intake.
Although CB(1)R activation modulates excitatory and inhibitory synaptic
transmission in the brain, CB(1)R contribution to the molecular architecture of
the excitatory and inhibitory synaptic terminals in the VMH is not known.
Therefore, the aim of this study was to investigate the precise subcellular
distribution of CB(1)R in the VMH to better understand the modulation exerted by
the endocannabinoid system on the complex brain circuitries converging into this
METHODOLOGY/PRINCIPAL FINDINGS: Light and electron microscopy techniques were
used to analyze CB(1)R distribution in the VMH of CB(1)R-WT, CB(1)R-KO and
conditional mutant mice bearing a selective deletion of CB(1)R in cortical
glutamatergic (Glu-CB(1)R-KO) or GABAergic neurons (GABA-CB(1)R-KO). At light
microscopy, CB(1)R immunolabeling was observed in the VMH of CB(1)R-WT and
Glu-CB(1)R-KO animals, being remarkably reduced in GABA-CB(1)R-KO mice. In the
electron microscope, CB(1)R appeared in membranes of both glutamatergic and
GABAergic terminals/preterminals. There was no significant difference in the
percentage of CB(1)R immunopositive profiles and CB(1)R density in terminals
making asymmetric or symmetric synapses in CB(1)R-WT mice. Furthermore, the
proportion of CB(1)R immunopositive terminals/preterminals in CB(1)R-WT and
Glu-CB(1)R-KO mice was reduced in GABA-CB(1)R-KO mutants. CB(1)R density was
similar in all animal conditions. Finally, the percentage of CB(1)R labeled
boutons making asymmetric synapses slightly decreased in Glu-CB(1)R-KO mutants
relative to CB(1)R-WT mice, indicating that CB(1)R was distributed in cortical
and subcortical excitatory synaptic terminals.
CONCLUSIONS/SIGNIFICANCE: Our anatomical results support the idea that the VMH is
a relevant hub candidate in the endocannabinoid-mediated modulation of the
excitatory and inhibitory neurotransmission of cortical and subcortical pathways
regulating essential hypothalamic functions for the individual’s survival such as
the feeding behavior.

DOI: 10.1371/journal.pone.0026167
PMCID: PMC3191179
PMID: 22022550 [Indexed for MEDLINE]

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