Biology Reference
In-Depth Information
climbing fibers. Pairing depolarization of a Purkinje cell with activation of a strongly-
innervating climbing fiber induces homosynaptic LTP, whereas that with activation of a
weakly-innervating climbing fiber induces homosynaptic LTD [82]. LTP and LTD in P6-9
rats were suggested to be involved in the developmental reduction of number of innervating
climbing fibers.
The suppression mechanism of transmitter release from parallel fibers, climbing fibers or
inhibitory interneurons triggered in a postsynaptic Purkinje cell has also been reported. When
a Purkinje cell is depolarized and/or the postsynaptic mGluR1 is activated, an
endocannabinoid called 2-arachidonoyl glycerol (2-AG) is released from the Purkinje cell
[83-87]. 2-AG suppresses the transmitter release through activation of presynaptic type 1
cannabinoid receptor (CB1R) for several tens of seconds. CB1R couples to heterotrimeric G
protein, which downregulates the voltage-gated Ca
2+
channel and increases the K
+
conductance through GIRK channel in the presynaptic terminal [88,89]. The depolarization-
induced suppression of glutamate release from parallel or climbing fibers is called DSE
(depolarization-induced suppression of excitation), and that of GABA from inhibitory
interneurons is called DSI (depolarization-induced suppression of inhibition). 2-AG is
catalyzed from DAG by DAG lipase, which is expressed in dendrites of a Purkinje cell
[90,91]. The release of 2-AG depends on the depolarization-induced elevation of Ca
2+
for
DSE and DSI, and on activation of the mGluR1/PLCβ signaling cascade for the suppression
induced by parallel-fiber activity [83-85,92]. Intracellular Ca
2+
elevation to a micromolar
range is required for DSE [93]. However, when mGluR1 is activated during depolarization,
less intracellular Ca
2+
elevation is sufficient to induce DSE [92]. PLCβ, which is
cooperatively activated by G
αq
and Ca
2+
, plays the integrative role [94].
There is also short-term (lasting for about 10 minutes) potentiation of GABA release
from inhibitory interneurons induced by depolarization of a postsynaptic Purkinje cell [95].
This phenomenon is called depolarization-induced potentiation of inhibition (DPI). DPI
induction depends on activation of the presynaptic NMDA receptor. Glutamate is released
from a Purkinje cell in response to depolarization, and serves as a retrograde messenger.
Glutamate causes the increase in intracellular Ca
2+
concentration in presynaptic terminals
through activation of NMDA receptor, facilitating the transmitter release [95,96].
LTP has also been reported at a mossy fiber - granule cell synapse. The high frequency
activation of mossy fibers paired with depolarization of the postsynaptic granule cell induces
LTP [97,98]. The LTP induction requires postsynaptic activation of NMDA receptor and the
consequent Ca
2+
influx. Implication of mGluR and PKC has also been reported. This form of
LTP is accompanied with the increase in amplitudes of both AMPA and NMDA receptor-
mediated current. The time course of NMDA receptor-mediated current is prolonged during
LTP, which could lead to the increased time window for temporal summation [97,99].
S
YNAPTIC
P
LASTICITY IN THE
DCN
A Purkinje cell directly inhibits neurons in DCN through GABAergic synapses. Both
LTP and LTD are reported at this synapse [100-102]. A DCN neuron exhibits rebound
depolarization and spike bursts after the offset of hyperpolarizing current [103]. This rebound
depolarization is mediated by low-threshold voltage-gated Ca
2+
channel [104]. A Purkinje cell
