Biology Reference
In-Depth Information
activates PKG, which in turn phosphorylates G-substrate. Phosphorylated G-substrate
suppresses protein phosphatases such as PP2A which counteracts kinases involved in the
LTD induction [48]. LTD is induced not only at synapses which are active during induction,
but also at nearby inactive synapses [49,50]. This heterosynaptic LTD is suggested to depend
on diffusion of nitric oxide [51,52].
Although δ2 subunit does not form an ion-conducting channel, it is grouped as an
ionotropic glutamate receptor according to its primary structure [53,54]. Extensive studies
have been conducted on this molecule. It is specifically expressed on the postsynaptic
membrane of parallel fiber - Purkinje cell synapses and is required for the LTD induction
[13,42,53-56]. δ2 knockout mouse shows not only LTD impairment but also reduced number
of parallel fiber synapses, motor incoordination and impaired motor learning [55,57-60].
Physiological ligand of δ2 has not been identified, although serine and glycine bind to δ2
[61,62]. LTD is also rescued in a δ2-null Purkinje cell by transfection of truncated δ2 subunit
that contains highly-charged membrane-proximal motif in the cytoplasmic region but not by
transfection of the mutant δ2 subunit without the charged motif [63]. δ2 subunit interacts with
PICK1 through this charged motif, and this interaction is required for the LTD induction.
Other studies demonstrated that the PDZ-binding motif in the C-terminus of δ2 subunit is also
required for the LTD induction [64,65]. Thus, δ2 seems to regulate the LTD induction
through the interaction with intracellular molecules, although the detail is enigmatic.
As described above, various molecules are involved in the LTD induction. However, it is
not clear how their interaction is regulated in the complex intracellular signaling cascade. A
computational simulation model of molecular signaling cascades involved in the LTD
induction has been constructed in an attempt to clarify the role of each molecule [37,66].
L
ONG
-T
ERM
P
OTENTIATION AND
O
THER
F
ORMS OF
S
YNAPTIC
P
LASTICITY
Synaptic plasticity in the cerebellar cortex
Long-term potentiation (LTP) is induced at the parallel fiber - Purkinje cell synapses by
repetitive stimulation of parallel fibers [8,67-71]. Two forms of LTP have been reported
(Figure 3).
One is accompanied with the increased glutamate release from the presynaptic terminal,
and the other with the increased postsynaptic glutamate responsiveness. The former is
induced by the 2-8 Hz repetitive stimulation, and the latter by the 1 Hz stimulation. While the
induction of presynaptic LTP depends on cyclic AMP (cAMP) in the presynaptic terminal,
the induction of postsynaptic LTP depends on NO and moderate increase in the postsynaptic
intracellular Ca
2+
concentration [69-71]. It is suggested that the postsynaptic LTP reverses the
cerebellar LTD by increasing the number of AMPA receptors on the postsynaptic membrane
[72].
Long-term synaptic plasticity is also reported at the GABAergic inhibitory synapses
between basket/stellate cells and a Purkinje cell. When a Purkinje cell is strongly depolarized,
for example by repetitive climbing fiber inputs, the efficacy of synaptic transmission is
potentiated for more than 30 minutes. [73]. This phenomenon is called rebound potentiation
