Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum

Motokazu Uchigashima, Madoka Narushima, Masahiro Fukaya, I. Katona, Masanobu Kano, Masahiko Watanabe

Research output: Contribution to journalArticle

269 Citations (Scopus)

Abstract

Endogenous cannabinoids (endocannabinoids) mediate retrograde signals for short- and long-term suppression of transmitter release at synapses of striatal medium spiny (MS) neurons. An endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is synthesized from diacylglycerol (DAG) after membrane depolarization and Gq-coupled receptor activation. To understand 2-AG-mediated retrograde signaling in the striatum, we determined precise subcellular distributions of the synthetic enzyme of 2-AG, DAG lipase-α (DAGLα), and its upstream metabotropic glutamate receptor 5 (mGluR5) and muscarinic acetylcholine receptor 1 (M1). DAGLα, mGluR5, and M1 were all richly distributed on the somatodendritic surface of MS neurons, but their subcellular distributions were different. Although mGluR5 and DAGLα levels were highest in spines and accumulated in the perisynaptic region, M1 level was lowest in spines and was rather excluded from the mGluR5-rich perisynaptic region. These subcellular arrangements suggest that mGluR5 and M1 might differentially affect endocannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) and depolarization- induced suppression of excitation (DSE) in MS neurons. Indeed, mGluR5 activation enhanced both DSI and DSE, whereas M1 activation enhanced DSI only. Importantly, DSI, DSE, and receptor-driven endocannabinoid-mediated suppression were all abolished by the DAG lipase inhibitor tetrahydrolipstatin, indicating 2-AG as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons. Accordingly, CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neurons and parvalbumin-positive interneurons and at low levels on excitatory corticostriatal afferents. Thus, endocannabinoid signaling molecules are arranged to modulate the excitability of the MS neuron effectively depending on cortical activity and cholinergic tone as measured by mGluR5 and M1 receptors, respectively.

Original languageEnglish
Pages (from-to)3663-3676
Number of pages14
JournalJournal of Neuroscience
Volume27
Issue number14
DOIs
Publication statusPublished - Apr 4 2007

Fingerprint

Metabotropic Glutamate 5 Receptor
Cannabinoids
Neurons
Lipoprotein Lipase
Lipase
Synapses
Spine
Corpus Striatum
Cannabinoid Receptor CB1
Parvalbumins
Diglycerides
Presynaptic Terminals
Muscarinic Receptors
Interneurons
2-arachidonylglycerol
Cholinergic Agents
Membranes
Enzymes

Keywords

  • 2-arachidonoyl-glycerol (2-AG)
  • CB
  • Diacylglycerol lipase (DAGL)
  • Endocannabinoid
  • Immunohistochemistry
  • mGluR5
  • Mouse
  • Muscarinic acetylcholine receptor M
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. / Uchigashima, Motokazu; Narushima, Madoka; Fukaya, Masahiro; Katona, I.; Kano, Masanobu; Watanabe, Masahiko.

In: Journal of Neuroscience, Vol. 27, No. 14, 04.04.2007, p. 3663-3676.

Research output: Contribution to journalArticle

Uchigashima, Motokazu ; Narushima, Madoka ; Fukaya, Masahiro ; Katona, I. ; Kano, Masanobu ; Watanabe, Masahiko. / Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 14. pp. 3663-3676.
@article{ca4f8aec59ea4490b1454f9be0745761,
title = "Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum",
abstract = "Endogenous cannabinoids (endocannabinoids) mediate retrograde signals for short- and long-term suppression of transmitter release at synapses of striatal medium spiny (MS) neurons. An endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is synthesized from diacylglycerol (DAG) after membrane depolarization and Gq-coupled receptor activation. To understand 2-AG-mediated retrograde signaling in the striatum, we determined precise subcellular distributions of the synthetic enzyme of 2-AG, DAG lipase-α (DAGLα), and its upstream metabotropic glutamate receptor 5 (mGluR5) and muscarinic acetylcholine receptor 1 (M1). DAGLα, mGluR5, and M1 were all richly distributed on the somatodendritic surface of MS neurons, but their subcellular distributions were different. Although mGluR5 and DAGLα levels were highest in spines and accumulated in the perisynaptic region, M1 level was lowest in spines and was rather excluded from the mGluR5-rich perisynaptic region. These subcellular arrangements suggest that mGluR5 and M1 might differentially affect endocannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) and depolarization- induced suppression of excitation (DSE) in MS neurons. Indeed, mGluR5 activation enhanced both DSI and DSE, whereas M1 activation enhanced DSI only. Importantly, DSI, DSE, and receptor-driven endocannabinoid-mediated suppression were all abolished by the DAG lipase inhibitor tetrahydrolipstatin, indicating 2-AG as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons. Accordingly, CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neurons and parvalbumin-positive interneurons and at low levels on excitatory corticostriatal afferents. Thus, endocannabinoid signaling molecules are arranged to modulate the excitability of the MS neuron effectively depending on cortical activity and cholinergic tone as measured by mGluR5 and M1 receptors, respectively.",
keywords = "2-arachidonoyl-glycerol (2-AG), CB, Diacylglycerol lipase (DAGL), Endocannabinoid, Immunohistochemistry, mGluR5, Mouse, Muscarinic acetylcholine receptor M, Striatum",
author = "Motokazu Uchigashima and Madoka Narushima and Masahiro Fukaya and I. Katona and Masanobu Kano and Masahiko Watanabe",
year = "2007",
month = "4",
day = "4",
doi = "10.1523/JNEUROSCI.0448-07.2007",
language = "English",
volume = "27",
pages = "3663--3676",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "14",

}

TY - JOUR

T1 - Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum

AU - Uchigashima, Motokazu

AU - Narushima, Madoka

AU - Fukaya, Masahiro

AU - Katona, I.

AU - Kano, Masanobu

AU - Watanabe, Masahiko

PY - 2007/4/4

Y1 - 2007/4/4

N2 - Endogenous cannabinoids (endocannabinoids) mediate retrograde signals for short- and long-term suppression of transmitter release at synapses of striatal medium spiny (MS) neurons. An endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is synthesized from diacylglycerol (DAG) after membrane depolarization and Gq-coupled receptor activation. To understand 2-AG-mediated retrograde signaling in the striatum, we determined precise subcellular distributions of the synthetic enzyme of 2-AG, DAG lipase-α (DAGLα), and its upstream metabotropic glutamate receptor 5 (mGluR5) and muscarinic acetylcholine receptor 1 (M1). DAGLα, mGluR5, and M1 were all richly distributed on the somatodendritic surface of MS neurons, but their subcellular distributions were different. Although mGluR5 and DAGLα levels were highest in spines and accumulated in the perisynaptic region, M1 level was lowest in spines and was rather excluded from the mGluR5-rich perisynaptic region. These subcellular arrangements suggest that mGluR5 and M1 might differentially affect endocannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) and depolarization- induced suppression of excitation (DSE) in MS neurons. Indeed, mGluR5 activation enhanced both DSI and DSE, whereas M1 activation enhanced DSI only. Importantly, DSI, DSE, and receptor-driven endocannabinoid-mediated suppression were all abolished by the DAG lipase inhibitor tetrahydrolipstatin, indicating 2-AG as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons. Accordingly, CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neurons and parvalbumin-positive interneurons and at low levels on excitatory corticostriatal afferents. Thus, endocannabinoid signaling molecules are arranged to modulate the excitability of the MS neuron effectively depending on cortical activity and cholinergic tone as measured by mGluR5 and M1 receptors, respectively.

AB - Endogenous cannabinoids (endocannabinoids) mediate retrograde signals for short- and long-term suppression of transmitter release at synapses of striatal medium spiny (MS) neurons. An endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is synthesized from diacylglycerol (DAG) after membrane depolarization and Gq-coupled receptor activation. To understand 2-AG-mediated retrograde signaling in the striatum, we determined precise subcellular distributions of the synthetic enzyme of 2-AG, DAG lipase-α (DAGLα), and its upstream metabotropic glutamate receptor 5 (mGluR5) and muscarinic acetylcholine receptor 1 (M1). DAGLα, mGluR5, and M1 were all richly distributed on the somatodendritic surface of MS neurons, but their subcellular distributions were different. Although mGluR5 and DAGLα levels were highest in spines and accumulated in the perisynaptic region, M1 level was lowest in spines and was rather excluded from the mGluR5-rich perisynaptic region. These subcellular arrangements suggest that mGluR5 and M1 might differentially affect endocannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) and depolarization- induced suppression of excitation (DSE) in MS neurons. Indeed, mGluR5 activation enhanced both DSI and DSE, whereas M1 activation enhanced DSI only. Importantly, DSI, DSE, and receptor-driven endocannabinoid-mediated suppression were all abolished by the DAG lipase inhibitor tetrahydrolipstatin, indicating 2-AG as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons. Accordingly, CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neurons and parvalbumin-positive interneurons and at low levels on excitatory corticostriatal afferents. Thus, endocannabinoid signaling molecules are arranged to modulate the excitability of the MS neuron effectively depending on cortical activity and cholinergic tone as measured by mGluR5 and M1 receptors, respectively.

KW - 2-arachidonoyl-glycerol (2-AG)

KW - CB

KW - Diacylglycerol lipase (DAGL)

KW - Endocannabinoid

KW - Immunohistochemistry

KW - mGluR5

KW - Mouse

KW - Muscarinic acetylcholine receptor M

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=34147145848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147145848&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0448-07.2007

DO - 10.1523/JNEUROSCI.0448-07.2007

M3 - Article

VL - 27

SP - 3663

EP - 3676

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 14

ER -