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epileptic tissue (Beck et al. 2000). Along this line, we have recently obtained data indicating
that saturation of LA-LTP, assessed through repeated spaced delivery of HFS, occurred at
lower levels in kindled as compared to sham-implanted animals, consistent with the
hypothesis of reduced capacity of further synaptic strengthening (Fig. 4). Similar data we
have found after alcohol withdrawal (see above).
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kindled [n = 6]
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Figure 4. Saturation in kindled and control animals. Different saturation level of LA-LTP in kindled
rats and in sham-implanted animals (control) in response to repeated spaced high frequency stimulation
of afferents within the LA (four times 2 x 100 Hz, interval 30 s with the spaced interval of 20 min).
Data points represent averaged amplitudes (mean ± SEM) of field potential amplitudes normalized with
respect to baseline values
It is commonly observed that repeated delivery of HFS leads to a gradually increasing
degree of induction of LTP up to saturation, and that an excessively large number of stimulus
trains is deleterious to LTP (Abraham and Huggett 1997). Therefore, for the first time we
have shown that the kindling procedure acts like a depotentiation process in the LA. Given
the phenomenon of metaplasticity, that is the capacity for LTP itself to change (Abraham and
Bear 1996), our data show that the kindling procedure as kind of metaplasticity influences the
saturation level in the amygdala. It has been shown for the hippocampal CA1 region that
over-stimulation transiently inhibits subsequent LTP induction through activation of VGCC
and of NMDA receptors (Abraham and Huggett 1997). A potential mechanism for this LTP
inhibition might be a long-lasting reduction in NMDA receptor-mediated responses by prior
stimulation. Our electrophysiological data in kindled rats provide an interesting parallel to the
conditioning deficits seen after kindling (Hannesson and Corcoran 2000; Ripley et al. 2003).
The entire set of electrophysiological and behavioral data might be reconciled by suggesting
that kindling increases efficiency of synaptic connections, leading to reduced capacity for
further plasticity. Furthermore, theta pulse stimulation (TPS) elicited LA-LTD in controls,
whereas the same stimulation protocol caused LTP in kindled rats (Schubert et al. 2005).
Similar results we have found in the hippocampal region CA1. In controls, TPS-induced LTD
can be reversed by HFS, whereas in kindled animals the strength of TPS-induced LA-LTP
was further increased by the subsequent HFS.
