Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

Karson, Miranda A.; Whittington, Kevin C.; Alger, Bradley E.

doi:10.1016/j.neuropharm.2007.06.023

Cited by 51 publications

(53 citation statements)

References 62 publications

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“…This study revealed that CCK acts on the two types of inhibitory inputs in the opposite ways, namely, activation of one type and inhibition of the other. In agreement with this notion, it was reported that CCK selectively suppresses carbachol-induced spontaneous IPSPs, which reflect the inputs from CB 1 -and CCK-positive basket cells (259). The CB 1 dependency of this effect remains to be determined.…”

Section: Hippocampussupporting

confidence: 56%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,318

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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Section: Hippocampussupporting

confidence: 56%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,318

1,431

View full text Add to dashboard Cite

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“…According to the 'Cnr1 receptor hypothesis', CCK activation of CCKBR initiates endocannabinoid synthesis, activating pre-synaptic Cnr1 on CCK-containing interneurons to inhibit GABA transmission. Separately, CCK strongly depolarizes parvalbumin interneurons via CCKBR, increasing firing frequency of inhibitory currents (Foldy et al, 2007;Karson et al, 2008;. Although our results suggest that CCKBR is downstream of Cnr1, cell-type specific behavioral studies will better clarify the differences in our respective models of a Cnr1-CCKBR interaction.…”

Section: Discussionmentioning

confidence: 72%

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Bowers

Ressler

2014

Neuropsychopharmacol

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Post-traumatic stress disorder (PTSD) is thought to develop, in part, from improper inhibition of fear. Accordingly, one of the most effective treatment strategies for PTSD is exposure-based psychotherapy. Ideally, neuroscience would inform adjunct therapies that target the neurotransmitter systems involved in extinction processes. Separate studies have implicated the cholecystokinin (CCK) and endocannabinoid systems in fear; however, there is a high degree of anatomical colocalization between the cannabinoid 1 receptor (Cnr1) and CCK in the basolateral amygdala (BLA), a brain region critical for emotion regulation. Although most research has focused on GABA and GABAergic plasticity as the mechanism by which Cnr1 mediates fear inhibition, we hypothesize that a functional interaction between Cnr1 and CCKB receptor (CCKBR) is critical for fear extinction processes. In this study, systemic pharmacological manipulation of the cannabinoid system modulated cued fear expression in C57BL/6J mice after consolidation of auditory fear conditioning. Knockout of the CCKBR, however, had no effect on fear-or anxiety-like behaviors. Nonetheless, administration of a Cnr1 antagonist increased freezing behavior during a cued fear expression test in wild-type subjects, but had no effect on freezing behavior in CCKBR knockout littermates. In addition, we found that Cnr1-positive fibers form perisomatic clusters around CCKBR-positive cell bodies in the BLA. These CCKBR-positive cells comprise a molecularly heterogenous population of excitatory and inhibitory neurons. These findings provide novel evidence that Cnr1 contributes to cued fear expression via an interaction with the CCK system. Dysfunctional Cnr1-CCKBR interactions might contribute to the etiology of, or result from, fear-related psychiatric disease.

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“…Similarly, agatoxin enhances the relative magnitude, although not the absolute magnitude, of DSI by blocking interneurons that are not susceptible to DSI (Lenz et al 1998). Alternatively, the greater suppression of GABA A eIPSPs in agatoxin could reflect the removal of a presynaptic interaction between different kinds of s. radiatum interneurons, as recently suggested (Karson et al 2008).…”

Section: Iltd In Conotoxin and Enhancement Of Mglur-initiated Eipsp Smentioning

confidence: 80%

“…It is not fully understood how different interneurons are regulated, or how they interact with each other, although various hypotheses are emerging (e.g., Buzsaki 2002;Gillies et al 2002;Hefft and Jonas 2005;Glickfeld and Scanziani 2006;Karson et al 2008). Hoffman and Lupica (2000) showed that the GABA A (but not the GABA B ) component of an evoked inhibitory postsynaptic current was sensitive to an exogenous cannabinoid agonist, while both components were sensitive to the selective µOR agonist, [D-Ala2, NMePhe4, Gly-ol5]-enkephalin (DAMGO).…”

Section: Introductionmentioning

confidence: 99%

“…Functional interactions between conotoxin-and agatoxin-sensitive interneurons have recently been described (Karson et al 2008). If functional classes of interneurons correspond to CB1R-expressing, or µOR-expressing interneurons, this would be important, as there are many different reports that cannabinoids and opioids show a bidirectional interaction in some behavioral experiments (see Maldonado and Rodriguez 2002 for review).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus

Lafourcade

Alger

2007

Psychopharmacology

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Rationale-Hippocampal interneurons release γ-aminobutyric acid (GABA) and produce fast GABA A -and slow GABA B -inhibitory postsynaptic potentials (IPSPs). The regulation of GABA B eIPSPs or the interneurons that produce them are not well understood. In addition, while both µ-opioid receptors (µORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.Objectives-This study tests the hypotheses that: (1) all interneurons can initiate both GABA A and GABA B inhibitory postsynaptic potentials; (2) GABA B responses are insensitive to mGluRtriggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABA B responses are produced by interneurons that express µOR; and (4) CB1R-dependent and µOR-dependent response interact.Materials and methods-Pharmacological and electrophysiological approaches were used in acute rat hippocampal slices. High resistance microelectrode recordings were made from pyramidal cells, while interneurons were stimulated extracellularly.Results-GABA B responses were found to be produced by interneurons that release GABA via either presynaptic N-type or P/Q-type calcium channels but that they are insensitive to suppression by eCBs or eCB-mediated iLTD. GABA B IPSPs were sensitive to suppression by a µOR agonist, suggesting a major source of GABA B responses is the µOR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a µOR agonist in 6/13 slices.Conclusions-GABA B responses cannot be produced by all interneurons. CB1R or µOR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R-and µOR-mediated responses can interact.

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Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

Cited by 51 publications

References 62 publications

Endocannabinoid-Mediated Control of Synaptic Transmission

Endocannabinoid-Mediated Control of Synaptic Transmission

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus

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