Brief Trains of Action Potentials Enhance Pyramidal Neuron Excitability Via Endocannabinoid-Mediated Suppression of Inhibition

Fortin, Dale A.; Trettel, Joseph; Levine, Eric S.

doi:10.1152/jn.00351.2004

Cited by 69 publications

(59 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DSI of CCh-sIPSPs was similarly abolished in WIN-treated cells (data not shown). This confirms previous findings that CCh-sIPSPs are predominantly generated by interneurons with the CB 1 receptor Varma et al, 2001;Fortin et al, 2004), and represents the first evidence that CCK-sIPSPs are generated by interneurons lacking the CB 1 receptor.…”

Section: Cannabinoid Sensitivitysupporting

confidence: 91%

See 1 more Smart Citation

Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

2008

View full text Add to dashboard Cite

Cholecystokinin (CCK) is the most abundant neuropeptide in the central nervous system. In the hippocampal CA1 region, CCK is co-localized with GABA in a subset of interneurons that synapse on pyramidal cell somata and apical dendrites. CCK-containing interneurons also uniquely express a high level of the cannabinoid receptor, CB 1 , and mediate the retrograde signaling process called DSI. Reported effects of CCK on inhibitory post-synaptic potentials (IPSPs) in hippocampus are inconsistent, and include both increases and decreases in activity. Hippocampal interneurons are very heterogeneous, and these results could be reconciled if CCK affected different interneurons in different ways. To test this prediction, we used sharp microelectrode recordings from pyramidal cells with ionotropic glutamate receptors blocked, and investigated the effects of CCK on pharmacologically distinct groups of IPSPs during long-term recordings. We find that CCK, acting via the CCK 2 receptor, increases some IPSPs and decreases others, and most significantly, that the affected IPSPs can be classified into two groups by their pharmacological properties. IPSPs that are increased by carbachol (CCh-sIPSPs), are depressed by CCK, ω-conotoxin GVIA, and endocannabinoids. IPSPs that are enhanced by CCK (CCK-sIPSPs) are blocked by ω-agatoxin IVA, and are unaffected by carbachol or endocannabinoids. Interestingly, a CCK 2 antagonist enhances CCh-sIPSPs, suggesting normally they may be partially suppressed by endogenous CCK. In summary, our data are compatible with the hypothesis that CCK has opposite actions on sIPSPs that originate from functionally distinct interneurons.

show abstract

Section: Cannabinoid Sensitivitysupporting

confidence: 91%

“…DSI dramatically reduces CCh-sIPSP/Cs (Pitler & Alger, 1992b;Alger et al, 1996;Martin & Alger, 1999;Fortin et al, 2004;Reich et al, 2005) an effect we confirmed in all 18 cells that were tested (e.g., Fig. 3A1).…”

Section: Cannabinoid Sensitivitysupporting

confidence: 72%

Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

2008

View full text Add to dashboard Cite

show abstract

“…This view is strengthened by the abundant perisomatic expression of CB 1 Rs in neocortical and PFC interneurons (Tsou et al, 1998;Marsicano and Lutz, 1999). Also, cannabinoids have been shown to increase cortical excitatory transmission and net spiking probability of pyramidal neurons in vivo (Pistis et al, 2001;Fortin et al, 2004), consistent with a concurrent increment of basal glutamate levels and decrement of basal GABA levels in prefrontocortical microdialysis experiments observed in anesthetized (Pistis et al, 2002) and awake (Ferraro et al, 2001) rats, as well as in prefrontocortical in vitro culture (Ferraro et al, 2001;Tomasini et al, 2002).…”

Section: Discussionmentioning

confidence: 66%

“…The action of WIN55,212-2 may be explained by an enhanced feedforward excitatory input along mPFC-DR monosynaptic projections to 5-HT neurons possibly driven by disinhibiting pyramidal neurons (Fortin et al, 2004). Disinhibition was likely engaged by CB 1 R inhibitory control of cortical interneurons (Trettel and Levine, 2002), in agreement with the G i/o -proteinlinked transduction mechanism known to be associated with it and the resultant inhibition of voltage-sensitive calcium channels Figure 6.…”

Section: Discussionmentioning

confidence: 66%

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Bambico¹,

Katz²,

Debonnel³

et al. 2007

J. Neurosci.

293

213

View full text Add to dashboard Cite

Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB 1 receptors (CB 1 Rs). The action of CB 1 R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB 1 R agonist WIN55, 212-2 [R(ϩ)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB 1 R dependent because it was blocked by the CB 1 R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB 1 R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB 1 R-independent mechanism. The CB 1 R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB 1 R-dependent antidepressantlike effect in the FST. These results demonstrate that CB 1 R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.

show abstract

“…Therefore, one of the most important challenges is to determine possible physiological modes of DSE-DSI induction. Hence, studies aimed at establishing the physiological patterns of synaptic activity required to induce endocannabinoid release have just started (Brown et al, 2003;Hampson et al, 2003;Fortin et al, 2004;Galante and Diana, 2004). Dopamine (DA) neurons of the ventral tegmental area (VTA) play a central role in motivation, reward-related behaviors, and cognition (Schultz, 2002).…”

Section: Introductionmentioning

confidence: 99%

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

Melis¹,

Perra²,

Muntoni³

et al. 2004

J. Neurosci.

230

179

View full text Add to dashboard Cite

Endocannabinoids form a novel class of retrograde messengers that modulate short-and long-term synaptic plasticity. Depolarizationinduced suppression of excitation (DSE) and inhibition (DSI) are the best characterized transient forms of endocannabinoid-mediated synaptic modulation. Stimulation protocols consisting of long-lasting voltage steps to the postsynaptic cell are routinely used to evoke DSE-DSI. Little is known, however, about more physiological conditions under which these molecules are released in vitro. Moreover, the occurrence in vivo of such forms of endocannabinoid-mediated modulation is still controversial. Here we show that physiologically relevant patterns of synaptic activity induce a transient suppression of excitatory transmission onto dopamine neurons in vitro. Accordingly, in vivo endocannabinoids depress the increase in firing and bursting activity evoked in dopamine neurons by prefrontal cortex stimulation. This phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol (2-AG), which activates presynaptic cannabinoid type 1 receptors. 2-AG synthesis involves activation of metabotropic glutamate receptors and Ca 2ϩ mobilization from intracellular stores. These findings indicate that dopamine neurons release 2-AG to shape afferent activity and ultimately their own firing pattern. This novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear relevance in the pathogenesis of neuropsychiatric disorders such as schizophrenia and addiction.

show abstract

Brief Trains of Action Potentials Enhance Pyramidal Neuron Excitability Via Endocannabinoid-Mediated Suppression of Inhibition

Cited by 69 publications

References 60 publications

Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

Contact Info

Product

Resources

About