Biology Reference
In-Depth Information
Synaptic depression in the cerebellum has been observed at glutamatergic synapses. A similar
mechanism operates in the hippocampus. As in the cerebellum, activation of postsynaptic
group I mGluRs depresses neurotransmitter release through EC-mediated retrograde
activation of presynaptic CB1 receptors. In contrast to the cerebellum, however, synaptic
depression in the hippocampus has been observed at GABAergic rather than at glutamatergic
synapses.
In addition to group I mGluRs, other types of Gq-coupled receptors also induce EC
release. Muscarinic acetylcholine receptors, which are coupled to Gq protein[70], induced
transient suppression of inhibitory synaptic transmission is mediated through release of ECs
in the hippocampus [111]. In the dorsal raphe nucleus, orexin receptor, another Gq/11-
coupled receptor, was found to drive EC release [82].
It should be noted here that EC release driven by these Gq-coupled receptors is dependent
on tissue specific PLCβ isoenzymes (PLCβ1-4). In the hippocampus, activation of Gq-
coupled receptors, such as mGluR1/5 and M1/M3 muscarinic receptors, stimulates PLCβ1
and induces the production and release of 2-AG through DAGL activity (Fig 5A). 2-AG then
activates presynaptic CB1 receptors and suppresses the GABA release [89]. Activation of I
mGluRs stimulates PLCβ4 in cerebellar purkinje cells and yields DAG, which is then
converted to 2-AG by DAGL (Fig 5B). Then, 2-AG is released from the postsynaptic neuron,
activates presynaptic CB1 receptors, and suppresses the glutamate release [128].
(c) Ca2+-Assisted Receptor-Driven EC release
This is another form of EC-mediated short-term plasticity. It is driven by two distinct
stimuli, Gq-coupled receptor activation and Ca
2+
elevation, which facilitate PLCβ dependent
and independent pathways respectively. It was noted that simultaneous elevation of Ca
2+
and
activation of either group I mGluR or muscarinic receptors, the amount of ECs released was
several times higher than the simple sum of the amounts released by individual stimuli
applied separately [157, 160].
This is partly due to Ca
2+
dependency of PLCβ [89, 128] and
this effect was completely eliminated in PLCβ knockout mice[89]. This mode of EC release
seems physiologically important, because mild Ca
2+
elevation and mild receptor activation,
both of which are subthreshold for inducing EC release when applied alone, can effectively
induce EC release when applied conjointly. In this Ca
2+
-assisted receptor driven EC release,
PLCβ detects the coincidence of Ca
2+
elevation reflecting postsynaptic activity and the
receptor activation reflecting presynaptic activity. In this regard, PLCβ and the EC signal can
work as a coincidence detector and a coincidence signal, respectively, for activity-dependent
synaptic plasticity.
(d) Synaptically Triggered EC Release
EC release during short-term plasticity could be induced experimentally by the
aforementioned three stimulation protocols. Under physiological conditions, the EC signaling
should be triggered by synaptic activities. It is important to understand the kind of synaptic
activity and the type of pathway could facilitate physiological relevant EC release. There are
several studies that examined EC release during synaptic activity. In the cerebellum, brief
bursts of PF stimulation (for example,50-100 Hz, 10 pulses) induced EC release from PCs
and suppressed the transmitter release from PF terminals [30, 128]. This type of synaptic
suppression was dependent on both mGluR1 activation and postsynaptic Ca
2+
elevation [128].
