Biology Reference
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demonstrated by quantitative real-time PCR (Lepicard et al. 2006). These results suggest that
the CaMKIIN-alpha inhibitor has a physiological role in controlling CaMKII activity from an
early stage of memory consolidation.
B. AMPA receptors
Although AMPAR functions - dependent on their subunit composition, associated
proteins (TARPs) and interacting proteins - could be very diverse, there is compelling
evidence that trafficking of AMPA receptors to and away from the synapse alters synaptic
strengths and plays an essential role in both, LTP and LTD (Malenka 2003). LTP at
hippocampal synapses is thought to involve the insertion of AMPA receptors into the
postsynaptic membrane. There is evidence implicating postsynaptic as well as presynaptic
changes in this process. These changes include:
(i)
addition of AMPA channels to the extrasynaptic membrane and diffusional
equilibrium of extrasynaptic receptors with synaptic receptors,
(ii)
sudden addition of AMPA channels to the synapse in large groups,
(iii)
a change in the mode of glutamate release (presumably from kiss-and-run to full
fusion), and
(iv)
a delayed increase in the number of vesicles released (Lisman and Raghavachari
2006).
It now appears safe to state that one of the essential mechanisms for the expression of
LA-LTP involves increasing the number of AMPARs in the membrane at synapses via
activity-dependent changes in AMPAR trafficking. Fear conditioning, for example, drives
AMPA receptors into the synapse of a large fraction of postsynaptic neurons in the LA
(Rumpel et al. 2005). Furthermore, Rumpel and colleagues have demonstrated that memory
was reduced if AMPA receptor synaptic incorporation was blocked in as few as 10 to 20% of
LA neurons.
Concerning the composition of the AMPA receptors, immunoreactivity for different
subunits of the AMPA receptor (GluR1, GluR2/3, and GluR4) has been shown for the
amygdala
.
Immunoreactivity for GluR1 and Glu2/3 is predominantly localized to dendritic
shafts and seems to be more intense than that of GluR4 due to heavy labeling of proximal
portions of dendrites. The distribution of GluR4 immunoreactivity is very similar to that of
NMDAR1: GluR4 was seen in presynaptic terminals, glia, and dendrites and was primarily
localized to spines (Farb et al. 1995). Whereas high expression of GluR2 mRNA has been
correlated with low calcium entry, recent work reveals that LTP in the amygdala and
Pavlovian fear conditioning induce similar changes in postsynaptic AMPA-type glutamate
receptors and that occluding these changes by viral-mediated overexpression of a dominant-
negative GluR1 construct attenuates both LTP and fear memory in rats (Maren 2005).
Furthermore, it recently has been shown in GluR1 and GluR3 gene deficient mice that GluR1
and GluR3 contributed to LTP in the cortico-LA pathway
,
whereas LTP at thalamic inputs to
LA projection neurons and at glutamatergic synapses in the basal amygdala was completely
absent in GluR1
-/-
mice
(Humeau et al. 2007). Since both auditory and contextual fear
conditioning were selectively impaired in GluR1
-/-
, but not GluR3
-/-
mice, the authors
