Endocannabinoid-Mediated Depolarization-Induced Suppression of Inhibition in Hilar Mossy Cells of the Rat Dentate Gyrus

Hofmann, Mackenzie E.; Nahir, Ben; Frazier, Charles J.

doi:10.1152/jn.00310.2006

Cited by 24 publications

(44 citation statements)

References 62 publications

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“…2 D, arrows). DGL␣ mRNA in MCs is likely consistent with depolarization-induced suppression of inhibition (DSI) in MCs (Hofmann et al, 2006). We also found low levels of DGL␣ mRNA in some interneurons expressing GAD67 mRNA (30 of 44 cells expressing GAD67 mRNA) (Fig.…”

Section: Dgl␣ Highly Accumulates In the Neck Portion Of Gc Spinessupporting

confidence: 69%

Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell–Granule Cell Synapses in the Dentate Gyrus

Uchigashima¹,

Yamazaki²,

Yamasaki³

et al. 2011

J. Neurosci.

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2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of neurotransmission in the brain. In the present study, we investigated the 2-AG signaling system at mossy cell (MC)-granule cell (GC) synapses in the mouse dentate gyrus, an excitatory recurrent circuit where endocannabinoids are thought to suppress epileptogenesis. First, we showed by electrophysiology that 2-AG produced by diacylglycerol lipase ␣ (DGL␣) mediated both depolarization-induced suppression of excitation and its enhancement by group I metabotropic glutamate receptor activation at MC-GC synapses, as they were abolished in DGL␣-knock-out mice. Immunohistochemistry revealed that DGL␣ was enriched in the neck portion of GC spines forming synapses with MC terminals, whereas cannabinoid CB 1 receptors accumulated in the terminal portion of MC axons. On the other hand, the major 2-AG-degrading enzyme, monoacylglycerol lipase (MGL), was absent at MC-GC synapses but was expressed in astrocytes and some inhibitory terminals. Serial electron microscopy clarified that a given GC spine was innervated by a single MC terminal and also contacted nonsynaptically by other MC terminals making synapses with other GC spines in the neighborhood. MGL-expressing elements, however, poorly covered GC spines, amounting to 17% of the total surface of GC spines by astrocytes and 4% by inhibitory terminals. Our findings provide a basis for 2-AG-mediated retrograde suppression of MC-GC synaptic transmission and also suggest that 2-AG released from activated GC spines is readily accessible to nearby MC-GC synapses by escaping from enzymatic degradation. This molecular-anatomical configuration will contribute to adjust network activity in the dentate gyrus after enhanced excitation.

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Section: Dgl␣ Highly Accumulates In the Neck Portion Of Gc Spinessupporting

confidence: 69%

Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell–Granule Cell Synapses in the Dentate Gyrus

Uchigashima¹,

Yamazaki²,

Yamasaki³

et al. 2011

J. Neurosci.

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“…The DSI in granule cells, mossy cells, and cultured hippocampal neurons was confirmed to be Ca 2ϩ dependent and CB 1 dependent (227,242,394). As for the ability of inhibitory neurons to induce DSI, different results have been reported.…”

Section: Hippocampusmentioning

confidence: 97%

“…By measuring spontaneous or evoked IPSCs/ IPSPs, neurophysiologists have shown that DSI can be induced in various hippocampal neurons including CA1 pyramidal cells (426,564), CA3 pyramidal cells (362), dentate granule cells (242), hilar mossy cells (227), CCKpositive interneurons (7), and cultured hippocampal neurons (394,397).…”

Section: Hippocampusmentioning

confidence: 99%

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Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,314

1,431

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The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

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“…Hilar mossy cells were identified using a number of anatomical and physiological characteristics, as previously described (Frazier et al 2003;Hofmann et al 2006). Briefly, a typical mossy cell appeared significantly larger than neighboring hilar cells when visualized under IR DIC, had a whole cell capacitance Ͼ200 pF, and displayed at least some large-amplitude (usually Ͼ100 pA) spontaneous excitatory postsynaptic currents (sEPSCs) when voltage clamped at Ϫ70 mV in the absence of glutamate receptor antagonists.…”

Section: Identification Of Mossy Cellsmentioning

confidence: 99%