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kindled animals 48 hours after the last of 7 consecutive stage-five seizures. In our
experiments the stimulation of GLU
K5
kainate receptors by ATPA caused a decrease in LA-
LTP in slices derived from male control animals. However, ATPA rescues kindling-induced
impairment of LA-LTP. The partial blockade of GABAergic transmission enhanced the
induction of LA-LTP in controls, but did not compensate for kindling-induced changes in the
magnitude of LTP (Schubert and Albrecht 2007). The LTP-enhancing effect of ATPA in
kindled animals suggests an up-regulation of GLU
K5
kainate receptors on projection neurons
similar to that described for the kainate model of epilepsy in the hippocampus (Ullal et al.
2005). As shown in Figure 5, we did not find that GLU
K5
stimulation enhanced LA-LTP in
pilocarpine-treated rats. Therefore, the LTP-enhancing effect of ATPA seems to be specific to
the kindling procedure.
C. The CNS renin-angiotensin system (RAS)
Aside from the classical functions of the renin-angiotensin system (RAS)
in salt and
water homeostasis and in the regulation of blood pressure, the RAS
in the CNS is also
involved in the regulation of multiple functions in the brain, including processes of sensory
information, learning and memory as well as regulation of emotional responses. Moreover,
there are growing evidences that the RAS is also involved in several neurodegenerative
diseases.
We could demonstrate that angiotensin II (Ang II) binds to neurons in the LA (von
Bohlen und Halbach and Albrecht 1998d). Furthermore, the presence of AT1 (von Bohlen
und Halbach and Albrecht 1998b), AT2 (Albrecht et al. 2000) and AT4 receptors within the
LA has been described (von Bohlen und Halbach and Albrecht 2000). Neuronal AT1
receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake,
and secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the
stimulation of apoptosis and as being antagonistic to AT1 receptors. In accordance with the
role of AT2 receptors in development, we have shown that cell densities in the LA are higher
in adult AT2-deficient in comparison to wildtype mice (von Bohlen und Halbach et al. 2001).
The amygdala is discussed in terms of its role in receiving afferent sensory input and in
processing information related to hydromineral balance. Angiotensin acts on and through the
amygdala to stimulate thirst and sodium appetite (Johnson and Thunhorst 1997). In
normotensive Sprague-Dawley rats, iontophoretically ejected Ang II induced a significant
increase in the discharge rate in responsive amygdaloid neurons. In contrast, in hypertensive,
transgenic [TGR(mREN-2)27] rats with higher brain Ang II level, Ang II more often caused
inhibitory effects on the amygdaloid firing rate in comparison to controls. Moreover, we have
shown that the responsiveness of amygdaloid neurons was significantly higher in transgenic
rats in comparison to controls (Albrecht et al. 2000). In addition, we have observed that Ang
II causes a suppression of LA-LTP (Albrecht et al. 2003; von Bohlen und Halbach and
Albrecht 1998a) as well as of LA-LTD (Tchekalarova and Albrecht 2007), whereas
angiotensin-(1-7) enhances LA-LTP (Albrecht 2007) through the G-protein-coupled receptor
Mas (Hellner et al. 2005). Actions of the RAS on synaptic plasticity seems not to be restricted
to the amygdala, since it has been shown that Ang II and angiotensin IV also influence
hippocampal LTP (Armstrong et al. 1996; Denny et al. 1991; Kramar et al. 2001; Wayner et
al. 2001).
