Presence of depolarization-induced suppression of inhibition in a fraction of GABAergic synaptic connections in rat neocortical cultures

Storozhuk, Maksim; Іванова, Світлана; Piomelli, Daniele

doi:10.1007/s11055-006-0077-x

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…Activation of CB 1 receptors by endocannabinoids is known to inhibit GABA release, thus accounting for the phenomenon of depolarization‐induced suppression of inhibition (DSI) (Pitler & Alger, 1994; Hájos et al, 2000; Yoshida et al, 2002; Storozhuk et al, 2006). A high GABAergic tone in the VBTNs facilitates the generation of SWDs (McCormick & Bal, 1997).…”

Section: Discussionmentioning

confidence: 99%

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

et al. 2010

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SUMMARYPurpose: Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB 1 ) receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of ''presymptomatic'' 2-month old and ''symptomatic'' 8-month-old WAG/Rij rats relative to agematched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB 1 receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB 1 receptor agonist, R(+)WIN55,212-2 (3-12 mg/kg, s.c.), given alone or combined with the CB 1 receptor antagonist/inverse agonist, AM251 (12 mg/kg, s.c.).Results: Data showed a reduction of CB 1 receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB 1 receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB 1 receptor agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB 1 receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB 1 receptors are targeted by novel antiabsence drugs.

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Section: Discussionmentioning

confidence: 99%

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

et al. 2010

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“…DSI has been reported in several types of cortical neurons, including layer 2/3 pyramidal cells (161,516,517) and layer 2 and 5 pyramidal cells (44) of the sensory cortex and cultured cortical neurons (488).…”

Section: Cerebral Cortexmentioning

confidence: 99%

“…The authors suggested that the majority of inhibitory inputs to layer 5 pyramidal cells are insensitive to cannabinoids. Storozhuk et al (488) reported DSI of cultured neocortical neurons. Depolarization (to Ϫ10 mV for 5 s) of postsynaptic neurons induced a transient suppression of unitary IPSCs, which was accompanied by an increase in the paired-pulse ratio.…”

Section: Cerebral Cortexmentioning

confidence: 99%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,298

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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TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling

Storozhuk

Zholos

2018

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Background: Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocannabinoid system may be a useful approach to pain alleviation. Classically, the system includes G protein-coupled receptors of the CB1 and CB2 subtypes and their endogenous ligands. More recently, several subtypes of the large superfamily of cation TRP channels have been coined as “ionotropic cannabinoid receptors”, thus highlighting their role in cannabinoid signalling. Thus, the aim of this review was to explore the intimate connection between several “painful” TRP channels, endocannabinoids and nociceptive signalling.Methods: Research literature on this topic was critically reviewed allowing us not only summarize the existing evidence in this area of research, but also propose several possible cellular mechanisms linking nociceptive and cannabinoid signaling with TRP channels.Results: We begin with an overview of physiology of the endocannabinoid system and its major components, namely CB1 and CB2 G protein-coupled receptors, their two most studied endogenous ligands, anandamide and 2-AG, and several enzymes involved in endocannabinoid biosynthesis and degradation. The role of different endocannabinoids in the regulation of synaptic transmission is then discussed in detail. The connection between the endocannabinoid system and several TRP channels, especially TRPV1-4, TRPA1 and TRPM8, is then explored, while highlighting the role of these same channels in pain signalling.Conclusion: There is increasing evidence implicating several TRP subtypes not only as an integral part of the endocannabinoid system, but also as promising molecular targets for pain alleviation with the use of endo- and phytocannabinoids, especially when the function of these channels is upregulated under inflammatory conditions.

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Presence of depolarization-induced suppression of inhibition in a fraction of GABAergic synaptic connections in rat neocortical cultures

Cited by 3 publications

References 24 publications

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

Endocannabinoid-Mediated Control of Synaptic Transmission

TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling

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Presence of depolarization-induced suppression of inhibition in a fraction of GABAergic synaptic connections in rat neocortical cultures

Cited by 3 publications

References 24 publications

WAG/Rij rats show a reduced expression of CB1 receptors in thalamic nuclei and respond to the CB1 receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

WAG/Rij rats show a reduced expression of CB1 receptors in thalamic nuclei and respond to the CB1 receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

Endocannabinoid-Mediated Control of Synaptic Transmission

TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling

Contact Info

Product

Resources

About

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges

WAG/Rij rats show a reduced expression of CB₁ receptors in thalamic nuclei and respond to the CB₁ receptor agonist, R(+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges