Chevaleyre V, Takahashi KA, Castillo PE. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29: 37-76
ABSTRACT Changes in synaptic efficacy are thought to be crucial to experience-dependent modifications of neural function. The diversity of mechanisms underlying these changes is far greater than previously expected. In the last five years, a new class of use-dependent synaptic plasticity that requires retrograde signaling by endocannabinoids (eCB) and presynaptic CB1 receptor activation has been identified in several brain structures. eCB-mediated plasticity encompasses many forms of transient and long-lasting synaptic depression and is found at both excitatory and inhibitory synapses. In addition, eCBs can modify the inducibility of non-eCB-mediated forms of plasticity. Thus, the eCB system is emerging as a major player in synaptic plasticity. Given the wide distribution of CB1 receptors in the CNS, the list of brain structures and synapses expressing eCB-mediated plasticity is likely to expand.
- SourceAvailable from: Eckhard Friauf
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- "Endocannabinoids are powerful key modulators of synaptic function, acting through retrograde signaling. Postsynaptic depolarizing activity results in synthesis and release of endocannabinoids (2-AG, 2-arachidonoyl glycerol) that activate presynaptic cannabinoid type receptors (CB1Rs, which are G protein-coupled receptors) and suppress neurotransmitter release by lowering P r via inactivation of I pCa at various Ca v channels (Chevaleyre et al. 2006; Regehr et al. 2009). The period of endocannabinoid-induced low P r can be brief (maximum at ~5–10 s; t 1/2 ~15–20 s) or last tens of minutes (Kreitzer and Regehr 2001; Chevaleyre et al. 2007). "
ABSTRACT: Synaptic transmission via chemical synapses is dynamic, i.e., the strength of postsynaptic responses may change considerably in response to repeated synaptic activation. Synaptic strength is increased during facilitation, augmentation and potentiation, whereas a decrease in synaptic strength is characteristic for depression and attenuation. This review attempts to discuss the literature on short-term and long-term synaptic plasticity in the auditory brainstem of mammals and birds. One hallmark of the auditory system, particularly the inner ear and lower brainstem stations, is information transfer through neurons that fire action potentials at very high frequency, thereby activating synapses >500 times per second. Some auditory synapses display morphological specializations of the presynaptic terminals, e.g., calyceal extensions, whereas other auditory synapses do not. The review focuses on short-term depression and short-term facilitation, i.e., plastic changes with durations in the millisecond range. Other types of short-term synaptic plasticity, e.g., posttetanic potentiation and depolarization-induced suppression of excitation, will be discussed much more briefly. The same holds true for subtypes of long-term plasticity, like prolonged depolarizations and spike-time-dependent plasticity. We also address forms of plasticity in the auditory brainstem that do not comprise synaptic plasticity in a strict sense, namely short-term suppression, paired tone facilitation, short-term adaptation, synaptic adaptation and neural adaptation. Finally, we perform a meta-analysis of 61 studies in which short-term depression (STD) in the auditory system is opposed to short-term depression at non-auditory synapses in order to compare high-frequency neurons with those that fire action potentials at a lower rate. This meta-analysis reveals considerably less STD in most auditory synapses than in non-auditory ones, enabling reliable, failure-free synaptic transmission even at frequencies >100 Hz. Surprisingly, the calyx of Held, arguably the best-investigated synapse in the central nervous system, depresses most robustly. It will be exciting to reveal the molecular mechanisms that set high-fidelity synapses apart from other synapses that function much less reliably.Cell and Tissue Research 04/2015; 361(1). DOI:10.1007/s00441-015-2176-x · 3.57 Impact Factor
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- "Because many forms of eCB-mediated LTD require mGluR signaling (for review, see Chevaleyre et al., 2006; Kano et al., 2009), we examined the effects of 7× TBS during bath application of the group I/group II mGluR antagonist E4CPG (500 µM). Interestingly, blocking mGluR signaling did not prevent 7× TBS from inducing iLTD at layer 2/3 inhibitory synapses (Fig. 2A). "
ABSTRACT: The endogenous cannabinoid (endocannabinoid) system is an important regulator of synaptic function. Endocannabinoids acutely modulate inhibitory and excitatory transmission, and also mediate long-term depression at GABAergic and glutamatergic synapses. Typically, endocannabinoid synthesis and release is stimulated by depolarization-induced calcium influx and/or activation of phospholipase-C (PLC) signaling triggered by mGluR activation. Recently it has been shown that brain-derived neurotrophic factor (BDNF) can also induce endocannabinoid release. Although there is growing evidence for cross-talk between BDNF and endocannabinoid signaling, little is known about the functional relevance of these interactions. In the present studies, we examined BDNF - endocannabinoid interactions in regulating activity-dependent long-term depression at inhibitory synapses (iLTD). We found that theta burst stimulation (TBS) in layer 2/3 of mouse somatosensory cortical slices can induce a form of endocannabinoid-mediated iLTD that is independent of metabotropic glutamate receptor (mGluR) activation. This endocannabinoid-dependent iLTD, however, requires endogenous BDNF-trkB signaling, as it is blocked by a trk tyrosine kinase inhibitor and by a trkB receptor antagonist, and also requires activation of diacylglycerol lipase (DAG-lipase, DGL). In addition, endocannabinoid-mediated iLTD can be induced by combining a subthreshold concentration of exogenous BDNF with weak TBS stimulation that by itself is insufficient to induce iLTD. Taken together, our results suggest that TBS can induce the release of endogenous BDNF, which triggers DGL-dependent endocannabinoid mobilization and cannabinoid receptor-dependent iLTD at layer 2/3 cortical synapses.02/2015; 2(2). DOI:10.1523/ENEURO.0029-14.2015
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- "Endocannabinoids are synthesized by postsynaptic neurons in response to increased Ca 2+ concentrations , action potential trains and metabotropic glutamate, dopamine, and acetylcholine receptor activation (Kano et al., 2009). Endocannabinoids travel retrogradely and activate CB1 receptor, a G-protein coupled receptor located mainly on presynaptic terminals, resulting in short or long term decreases in GABA release (Piomelli, 2003; Chevaleyre et al., 2006). Another form of desinhibition by retrograde signaling is mediated by postsynaptic somatodendritic glutamate release and activation of presynaptic metabotropic glutamate receptors (Zilberter, 2000). "
ABSTRACT: Inhibitory transmission through the neurotransmitter γ-aminobutyric acid (GABA) shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.Frontiers in Cellular Neuroscience 10/2014; 8. DOI:10.3389/fncel.2014.00327 · 4.29 Impact Factor