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Article: Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence.

Rico-Barrio, Irantzu / Peñasco, Sara / Lekunberri, Leire / Serrano, Maitane / Egaña-Huguet, Jon / Mimenza, Amaia / Soria-Gomez, Edgar / Ramos, Almudena / Buceta, Ianire / Gerrikagoitia, Inmaculada / Mendizabal-Zubiaga, Juan / Elezgarai, Izaskun / Puente, Nagore / Grandes, Pedro

Biomedicines

2021 Volume 9, Issue 7

Abstract: Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, ... ...

Abstract	Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.
Language	English
Publishing date	2021-07-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9070825
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Article ; Online: Suppression of Presynaptic Glutamate Release by Postsynaptic Metabotropic NMDA Receptor Signalling to Pannexin-1.

Bialecki, Jennifer / Werner, Allison / Weilinger, Nicholas L / Tucker, Catharine M / Vecchiarelli, Haley A / Egaña, Jon / Mendizabal-Zubiaga, Juan / Grandes, Pedro / Hill, Matthew N / Thompson, Roger J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2019 Volume 40, Issue 4, Page(s) 729–742

Abstract: The impact of pannexin-1 (Panx1) channels on synaptic transmission is poorly understood. Here, we show that selective block of Panx1 in single postsynaptic hippocampal CA1 neurons from male rat or mouse brain slices causes intermittent, seconds long ... ...

Abstract	The impact of pannexin-1 (Panx1) channels on synaptic transmission is poorly understood. Here, we show that selective block of Panx1 in single postsynaptic hippocampal CA1 neurons from male rat or mouse brain slices causes intermittent, seconds long increases in the frequency of sEPSC following Schaffer collateral stimulation. The increase in sEPSC frequency occurred without an effect on evoked neurotransmission. Consistent with a presynaptic origin of the augmented glutamate release, the increased sEPSC frequency was prevented by bath-applied EGTA-AM or TTX. Manipulation of a previously described metabotropic NMDAR pathway (i.e., by preventing ligand binding to NMDARs with competitive antagonists or blocking downstream Src kinase) also increased sEPSC frequency similar to that seen when Panx1 was blocked. This facilitated glutamate release was absent in transient receptor potential vanilloid 1 (TRPV1) KO mice and prevented by the TRPV1 antagonist, capsazepine, suggesting it required presynaptic TRPV1. We show presynaptic expression of TRPV1 by immunoelectron microscopy and link TRPV1 to Panx1 because Panx1 block increases tissue levels of the endovanilloid, anandamide. Together, these findings demonstrate an unexpected role for metabotropic NMDARs and postsynaptic Panx1 in suppression of facilitated glutamate neurotransmission.
MeSH term(s)	Animals ; Calcium Chelating Agents/pharmacology ; Connexins/metabolism ; Egtazic Acid/analogs & derivatives ; Egtazic Acid/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Glutamic Acid/metabolism ; Hippocampus/drug effects ; Hippocampus/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Presynaptic Terminals/drug effects ; Presynaptic Terminals/metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Sodium Channel Blockers/pharmacology ; Synapses/drug effects ; Synapses/metabolism ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; Tetrodotoxin/pharmacology ; src-Family Kinases/metabolism
Chemical Substances	Calcium Chelating Agents ; Connexins ; Nerve Tissue Proteins ; Panx1 protein, mouse ; Receptors, N-Methyl-D-Aspartate ; Sodium Channel Blockers ; TRPV Cation Channels ; TRPV1 protein, mouse ; Glutamic Acid (3KX376GY7L) ; Tetrodotoxin (4368-28-9) ; Egtazic Acid (526U7A2651) ; EGTA acetoxymethyl ester (99590-86-0) ; src-Family Kinases (EC 2.7.10.2)
Language	English
Publishing date	2019-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0257-19.2019
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Article ; Online: Visualization by high resolution immunoelectron microscopy of the transient receptor potential vanilloid-1 at inhibitory synapses of the mouse dentate gyrus.

Canduela, Miren-Josune / Mendizabal-Zubiaga, Juan / Puente, Nagore / Reguero, Leire / Elezgarai, Izaskun / Ramos-Uriarte, Almudena / Gerrikagoitia, Inmaculada / Grandes, Pedro

PloS one

2015 Volume 10, Issue 3, Page(s) e0119401

Abstract: We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the ... ...

Abstract	We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML). In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (∼60% of total immunoparticles) at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.
MeSH term(s)	Animals ; Cell Body/metabolism ; Dendrites/metabolism ; Dentate Gyrus/metabolism ; Female ; Gene Knockout Techniques ; Inhibitory Postsynaptic Potentials ; Male ; Mice ; Microscopy, Immunoelectron ; Synapses/metabolism ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0119401
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Article ; Online: The transient receptor potential vanilloid-1 is localized at excitatory synapses in the mouse dentate gyrus.

Puente, Nagore / Reguero, Leire / Elezgarai, Izaskun / Canduela, Miren-Josune / Mendizabal-Zubiaga, Juan / Ramos-Uriarte, Almudena / Fernández-Espejo, Emilio / Grandes, Pedro

Brain structure & function

2015 Volume 220, Issue 2, Page(s) 1187–1194

Abstract: The transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that plays an important role in pain perception and modulates neurotransmitter release and synaptic plasticity in the brain. TRPV1 function must lay on its ... ...

Abstract	The transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that plays an important role in pain perception and modulates neurotransmitter release and synaptic plasticity in the brain. TRPV1 function must lay on its anatomical distribution in the peripheral and central nervous system regions involved in the physiological roles of the channel. However, the anatomical localization of TRPV1 is well established in the periphery, but in the brain it is a matter of debate. While some studies support the presence of TRPV1 in several brain regions, recent evidences suggest a restricted distribution of the channel in the central nervous system. To investigate to what extent central TRPV1 function stands on a precise brain distribution of the channel, we examined the mouse hippocampal dentate molecular layer (ML) where TRPV1 mediates long-term synaptic plasticity. Using pre-embedding immunocytochemistry for high resolution electron microscopy, we show that TRPV1 immunoparticles are highly concentrated in postsynaptic dendritic spines to asymmetric perforant path synapses in the outer 2/3 of the ML. However, TRPV1 is poorly expressed at the excitatory hilar mossy cell synapses in the inner 1/3 of this layer. Importantly, the TRPV1 pattern distribution disappeared in the ML of TRPV1-knockout mice. Taken together, these findings support the notion of the presence of TRPV1 in a brain region where the channel has been shown to have a functional role, such as the perforant path synapses in the hippocampal dentate ML.
MeSH term(s)	Animals ; Dentate Gyrus/cytology ; Dentate Gyrus/metabolism ; Dentate Gyrus/ultrastructure ; Electrical Synapses/metabolism ; Electrical Synapses/ultrastructure ; Excitatory Postsynaptic Potentials ; Female ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Perforant Pathway/cytology ; Perforant Pathway/metabolism ; Perforant Pathway/ultrastructure ; TRPV Cation Channels/deficiency ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse
Language	English
Publishing date	2015-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-014-0711-2
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Article: The underside of the cerebral cortex: layer V/VI spiny inverted neurons.

Mendizabal-Zubiaga, Juan L / Reblet, Concepcion / Bueno-Lopez, Jose L

Journal of anatomy

2007 Volume 211, Issue 2, Page(s) 223–236

Abstract: This paper presents an account of past and current research on spiny inverted neurons--alternatively also known as 'inverted pyramidal neurons'--in rats, rabbits and cats. In our laboratory, we have studied these cells with a battery of techniques suited ...

Abstract	This paper presents an account of past and current research on spiny inverted neurons--alternatively also known as 'inverted pyramidal neurons'--in rats, rabbits and cats. In our laboratory, we have studied these cells with a battery of techniques suited for light and electron microscopy, including Nissl staining, Golgi impregnation, dye intracellular filling and axon retrograde track-tracing. Our results show that spiny inverted neurons make up less than 8.5 and 5.5% of all cortical neurons in the primary and secondary rabbit visual cortex, respectively. Infragranular spiny inverted neurons constitute 15 and 8.5% of infragranular neurons in the same animal and areas. Spiny inverted neurons congregate at layers V-VI in all studied species. Studies have also revealed that spiny inverted neurons are excitatory neurons which furnish axons for various cortico-cortical, cortico-claustral and cortico-striatal projections, but not for non-telencephalic centres such as the lateral and medial geniculate nuclei, the colliculi or the pons. As a group, each subset of inverted cells contributing to a given projection is located below the pyramidal neurons whose axons furnish the same centre. Spiny inverted neurons are particularly conspicuous as a source of the backward cortico-cortical projection to primary visual cortex and from this to the claustrum. Indeed, they constitute up to 82% of the infragranular cells that furnish these projections. Spiny inverted neurons may be classified into three subtypes according to the point of origin of the axon on the cell: the somatic basal pole which faces the cortical outer surface, the somatic flank and the reverse apical dendrite. As seen with electron microscopy, the axon initial segments of these subtypes are distinct from one another, not only in length and thickness, but also in the number of received synaptic boutons. All of these anatomical features together may support a synaptic-input integration which is peculiar to spiny inverted neurons. In this way, two differently qualified streams of axonal output may coexist in a projection which arises from a particular infragranular point within a given cortical area; one stream would be furnished by the typical pyramidal neurons, whereas spiny inverted neurons would constitute the other source of distinct information flow.
MeSH term(s)	Animals ; Axons/physiology ; Axons/ultrastructure ; Cats ; Cerebral Cortex/anatomy & histology ; Cerebral Cortex/cytology ; Membrane Potentials/physiology ; Pyramidal Cells/cytology ; Pyramidal Cells/physiology ; Rabbits ; Rats ; Synapses/physiology ; Synapses/ultrastructure
Language	English
Publishing date	2007-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2955-5
ISSN	1469-7580 ; 0021-8782
ISSN (online)	1469-7580
ISSN	0021-8782
DOI	10.1111/j.1469-7580.2007.00779.x
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Article ; Online: Cognitive and neurobehavioral benefits of an enriched environment on young adult mice after chronic ethanol consumption during adolescence.

Rico-Barrio, Irantzu / Peñasco, Sara / Puente, Nagore / Ramos, Almudena / Fontaine, Christine J / Reguero, Leire / Giordano, Maria Elvira / Buceta, Ianire / Terradillos, Itziar / Lekunberri, Leire / Mendizabal-Zubiaga, Juan / Rodríguez de Fonseca, Fernando / Gerrikagoitia, Inmaculada / Elezgarai, Izaskun / Grandes, Pedro

Addiction biology

2018 Volume 24, Issue 5, Page(s) 969–980

Abstract: Binge drinking (BD) is a common pattern of ethanol (EtOH) consumption by adolescents. The brain effects of the acute EtOH exposure are well-studied; however, the long-lasting cognitive and neurobehavioral consequences of BD during adolescence are only ... ...

Abstract	Binge drinking (BD) is a common pattern of ethanol (EtOH) consumption by adolescents. The brain effects of the acute EtOH exposure are well-studied; however, the long-lasting cognitive and neurobehavioral consequences of BD during adolescence are only beginning to be elucidated. Environmental enrichment (EE) has long been known for its benefits on the brain and may serve as a potential supportive therapy following EtOH exposure. In this study, we hypothesized that EE may have potential benefits on the cognitive deficits associated with BD EtOH consumption. Four-week-old C57BL/6J male mice were exposed to EtOH following an intermittent 4-day drinking-in-the-dark procedure for 4 weeks. Then they were exposed to EE during EtOH withdrawal for 2 weeks followed by a behavioral battery of tests including novel object recognition, novel location, object-in-place, rotarod, beam walking balance, tail suspension, light-dark box and open field that were run during early adulthood. Young adult mice exposed to EE significantly recovered recognition, spatial and associative memory as well as motor coordination skills and balance that were significantly impaired after adolescent EtOH drinking with respect to controls. No significant permanent anxiety or depressive-like behaviors were observed. Taken together, an EE exerts positive effects on the long-term negative cognitive deficits as a result of EtOH consumption during adolescence.
MeSH term(s)	Alcohol Drinking/adverse effects ; Alcohol Drinking/physiopathology ; Animals ; Binge Drinking/complications ; Binge Drinking/physiopathology ; Central Nervous System Depressants/pharmacology ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/physiopathology ; Darkness ; Ethanol/pharmacology ; Exploratory Behavior/drug effects ; Housing, Animal ; Lighting ; Male ; Mice, Inbred C57BL ; Postural Balance/drug effects ; Psychomotor Disorders/chemically induced ; Psychomotor Disorders/physiopathology ; Random Allocation ; Sensation Disorders/chemically induced ; Sensation Disorders/physiopathology
Chemical Substances	Central Nervous System Depressants ; Ethanol (3K9958V90M)
Language	English
Publishing date	2018-08-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1324314-7
ISSN	1369-1600 ; 1355-6215
ISSN (online)	1369-1600
ISSN	1355-6215
DOI	10.1111/adb.12667
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Zs.A 4586: Show issues

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Article ; Online: Precise localization of the voltage-gated potassium channel subunits Kv3.1b and Kv3.3 revealed in the molecular layer of the rat cerebellar cortex by a pre-embedding immunogold method.

Puente, Nagore / Mendizabal-Zubiaga, Juan / Elezgarai, Izaskun / Reguero, Leire / Buceta, Ianire / Grandes, Pedro

Histochemistry and cell biology

2010 Volume 134, Issue 4, Page(s) 403–409

Abstract: A proper motor activity relies on a correct cerebellar function. The Kv3.1 and Kv3.3 voltage-gated potassium channels are key proteins involved in cerebellar function and dysfunction, as the lack of these causes severe motor deficits. Both channel ... ...

Abstract	A proper motor activity relies on a correct cerebellar function. The Kv3.1 and Kv3.3 voltage-gated potassium channels are key proteins involved in cerebellar function and dysfunction, as the lack of these causes severe motor deficits. Both channel subunits are coexpressed in granule cells and are rapidly activated at relatively positive potentials to support the generation of fast action potentials. However, the contribution of each subunit to the molecular architecture of the parallel fibers, the granule cell axons, is so far unknown. The goal of this study was to elucidate the relative distribution of Kv3.1b and Kv3.3 in specific compartments of the rat parallel fibers by using a pre-embedding immunocytochemical method for electron microscopy. Numerous Kv3.1b and Kv3.3 silver-intensified gold particles were associated with membranes of parallel fiber synaptic terminals and their intervaricose segments. Kv3.1b was found in about 85% of parallel fiber synaptic terminals and in about 47% of their intervaricose portions. However, only 28% of intervaricosities and 23% of parallel fiber presynaptic boutons were Kv3.3 immunopositive. The analysis also revealed that 54% of Purkinje cell dendritic spines localized Kv3.3. Although both potassium channel subunits share localization in the same presynaptic parallel fiber compartments, the present results with the method used indicate that there are a higher percentage of parallel fibers labeled for Kv3.1b than for Kv3.3, and that the labeling intensity for each subunit is higher in specific subcompartments analyzed than in others.
MeSH term(s)	Animals ; Cerebellar Cortex/chemistry ; Cerebellar Cortex/metabolism ; Immunohistochemistry/methods ; Microscopy, Electron ; Nerve Fibers/metabolism ; Nerve Tissue Proteins/metabolism ; Neurons/chemistry ; Neurons/metabolism ; Presynaptic Terminals/metabolism ; Purkinje Cells/metabolism ; Rats ; Rats, Sprague-Dawley ; Shaw Potassium Channels/metabolism
Chemical Substances	Kcnc1 protein, rat ; Kcnc3 protein, rat ; Nerve Tissue Proteins ; Shaw Potassium Channels
Language	English
Publishing date	2010-09-21
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1222930-1
ISSN	1432-119X ; 0301-5564 ; 0948-6143
ISSN (online)	1432-119X
ISSN	0301-5564 ; 0948-6143
DOI	10.1007/s00418-010-0742-6
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Article: Cannabinoid CB

Mendizabal-Zubiaga, Juan / Melser, Su / Bénard, Giovanni / Ramos, Almudena / Reguero, Leire / Arrabal, Sergio / Elezgarai, Izaskun / Gerrikagoitia, Inmaculada / Suarez, Juan / Rodríguez De Fonseca, Fernando / Puente, Nagore / Marsicano, Giovanni / Grandes, Pedro

Frontiers in physiology

2016 Volume 7, Page(s) 476

Abstract: The cannabinoid type 1 ( ... ...

Abstract	The cannabinoid type 1 (CB
Language	English
Publishing date	2016-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2016.00476
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Article ; Online: Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus.

Glia

2018 Volume 66, Issue 7, Page(s) 1417–1431

Abstract: Astroglial type-1 cannabinoid ( ... ...

Abstract	Astroglial type-1 cannabinoid (CB
MeSH term(s)	Animals ; Astrocytes/metabolism ; Astrocytes/ultrastructure ; Glial Fibrillary Acidic Protein/genetics ; Glial Fibrillary Acidic Protein/metabolism ; Hippocampus/metabolism ; Hippocampus/ultrastructure ; Immunoenzyme Techniques ; Mice, Knockout ; Microscopy, Immunoelectron ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Receptor, Cannabinoid, CB1/genetics ; Receptor, Cannabinoid, CB1/metabolism
Chemical Substances	CNR1 protein, mouse ; Glial Fibrillary Acidic Protein ; Receptor, Cannabinoid, CB1 ; glial fibrillary astrocytic protein, mouse
Language	English
Publishing date	2018-02-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639414-0
ISSN	1098-1136 ; 0894-1491
ISSN (online)	1098-1136
ISSN	0894-1491
DOI	10.1002/glia.23314
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Article ; Online: GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

Reguero, Leire / Puente, Nagore / Elezgarai, Izaskun / Mendizabal-Zubiaga, Juan / Canduela, Miren Josune / Buceta, Ianire / Ramos, Almudena / Suárez, Juan / Rodríguez de Fonseca, Fernando / Marsicano, Giovanni / Grandes, Pedro

PloS one

2011 Volume 6, Issue 10, Page(s) e26167

Abstract: 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 ... ...

Abstract	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 nucleus. 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.
MeSH term(s)	Animals ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; GABAergic Neurons/metabolism ; Glutamic Acid/metabolism ; Immunohistochemistry ; Mice ; Mice, Knockout ; Presynaptic Terminals/metabolism ; Presynaptic Terminals/ultrastructure ; Receptor, Cannabinoid, CB1/metabolism ; Ventromedial Hypothalamic Nucleus/cytology ; Ventromedial Hypothalamic Nucleus/metabolism ; Ventromedial Hypothalamic Nucleus/ultrastructure ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Receptor, Cannabinoid, CB1 ; Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2011-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0026167
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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

Order via subito

Full text online

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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

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