Biology Reference
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The intracellular calcium concentration seems to be a crucial determinant of the polarity
and magnitude of long-term synaptic plasticity, in that low levels of calcium via activation of
calcium-dependent phosphatases facilitate LTD, whereas a shift towards higher calcium
levels triggers LTP via protein kinase pathways (Kirkwood and Bear 1995). Interestingly,
recently it has been shown that LFS also elicited a long-lasting potentiation in the LA in
slices derived from fear-conditioned rats (Schroeder and Shinnick-Gallagher 2004).
Therefore, kindling differentially affects the magnitude, saturation and polarity of LTP in LA
and CA1, respectively, most likely indicating an activity-dependent mechanism in the context
of synaptic metaplasticity. Kindling-evoked seizure activity may thus prime synapses via
calcium-dependent mechanisms, thereby affecting threshold, magnitude and saturation of
long-term plasticity at these synapses.
This sort of metaplasticity may then contribute to the
alteration in memory performance and emotional behaviour observed in TLE patients.
250
200
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50
control [n = 13]
2 µM ATPA [n = 13]
HFS
0
-30
-20
-10
0
10
20
30
40
50
60
min
Figure 5. Stimulation of kainate GLUK5 receptors by ATPA did not change the magnitude of LA-LTP
induced by high frequency stimulation of afferents within the LA of brain slices derived from
pilocarpine-treated, chronic epileptic rats. Data points represent averaged amplitudes (mean ± SEM)
normalized with respect to baseline values.
Although a significant reduction of cell density and the appearance of degenerated fibers
was evident in the LA after 15 times stage V seizures in BLA-kindled rats (von Bohlen und
Halbach et al. 2004), the observed impairment of LA-LTP in kindled animals might also be a
result of functional changes such as the up- or down-regulation of transmitter receptors,
involved in mediation of plasticity in the amygdala. Although different transmitter systems
are modified after kindling, we focused on the role of GLU
K5
kainate receptors in kindled
animals. It is known that GLU
K5
kainate receptor antagonists prevent hippocampal seizures
induced by pilocarpine or electrical stimulation in rats, both in vitro and in vivo (Smolders et
al. 2002). High concentrations of the selective GLU
K5
kainate receptor agonist ATPA induce
spontaneous epileptiform bursting in rat amygdala slices (Li et al. 2001) and limbic status
epilepticus when infused intravenously or when applied directly into the rat amygdala
(Kaminski et al. 2004; Rogawski et al. 2003). We used intra- and extracellular recordings of
LA neurons to study the role of kainate GLU
K5
receptors as modulators of synaptic
transmission and plasticity in brain slices derived from age-matched controls and from
