Timing dependence of the induction of cerebellar LTD

Safo, Patrick; Regehr, Wade G.

doi:10.1016/j.neuropharm.2007.05.029

Cited by 88 publications

(108 citation statements)

References 31 publications

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“…LTP is most often studied at room temperature using a prolonged low frequency stimulation (8 Hz for 15 s) (Salin et al 1996;van Beugen et al 2006). For our high temperature experiments and PF stimuli (bursts of 10 stimuli at 100 Hz), the extent of LTP is ϳ10%, seemingly insufficient to mask LTD (Safo and Regehr 2008).…”

Section: Discussionmentioning

confidence: 80%

Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses

Carey

Myoga

McDaniels

et al. 2011

Journal of Neurophysiology

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Endocannabinoids are potent regulators of synaptic strength. They are generally thought to modify neurotransmitter release through retrograde activation of presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs regulate several forms of synaptic plasticity at synapses onto Purkinje cells, including presynaptically expressed short-term plasticity and, somewhat paradoxically, a postsynaptic form of long-term depression (LTD). Here we have generated mice in which CB1Rs were selectively eliminated from cerebellar granule cells, whose axons form parallel fibers. We find that in these mice, endocannabinoid-dependent short-term plasticity is eliminated at parallel fiber, but not inhibitory interneuron, synapses onto Purkinje cells. Further, parallel fiber LTD is not observed in these mice, indicating that presynaptic CB1Rs regulate long-term plasticity at this synapse.

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Section: Discussionmentioning

confidence: 80%

Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses

Carey

Myoga

McDaniels

et al. 2011

Journal of Neurophysiology

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“…The study on eCB-STD clearly demonstrated that the endocannabinoid release was sharply dependent on the timing of PF and CF activation (51). The eCB-LTD exhibited a similar timing dependence, and LTP was most effectively induced when CF activity followed PF activity by ϳ80 ms (454). These data strongly suggest that the property of endocannabinoid release determines the timing dependence of cerebellar LTD.…”

Section: Cerebellummentioning

confidence: 78%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,268

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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“…LTD was induced in the current-clamp mode for 5 min with the protocol of 30 repeated parallel fiber bursts and single climbing fiber pairing every 10 s (Safo and Regehr, 2008). In the presence of SKF96365, LTD was blocked ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression

et al. 2012

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In the cerebellum, synaptic strength at the synapses between parallel fibers and Purkinje cells is best known to be modulated via metabotropic glutamate receptor 1 (mGluR1)-dependent cerebellar long-term depression (LTD). An increase in intracellular calcium levels plays an important role in inducing mGluR1-dependent cerebellar LTD. Downstream of mGluR1, there are two major sources of calcium: transient receptor potential canonical (TRPC) channels and inositol trisphosphate receptors (IP 3 R). IP 3 R triggers a calcium release from the intracellular calcium store. Here, we show that TRPC channels mediate mGluR1-evoked slow currents to regulate cerebellar LTD in Sprague Dawley rats. We found that the inhibition of TRPC channels blocks the induction of cerebellar LTD. Moreover, we show that processes known to underlie cerebellar LTD induction, such as increases in intracellular calcium concentration, the activation of protein kinase C, and the internalization of GluR2, are also hindered by blocking TRPC. These results suggest that the mGluR1-evoked activation of TRPC channels is required for the induction of cerebellar LTD.

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Timing dependence of the induction of cerebellar LTD

Cited by 88 publications

References 31 publications

Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses

Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses

Endocannabinoid-Mediated Control of Synaptic Transmission

Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression

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