Biology Reference
In-Depth Information
Considering the Mas receptor as one of the receptors for Ang-(1-7), it is important to note
that Mas can hetero-oligomerize with the AT1 receptor and, by doing so, inhibits the actions
of Ang II (Kostenis et al. 2005). This is a novel demonstration that a G-protein-coupled
receptor acts as a physiological antagonist of a previously characterized receptor. These data
also support our results obtained in the LA. We analyzed whether field potentials are altered
by Ang II in brain slices. Opposite actions of Ang II were obtained in mice lacking the Mas-
protooncogene, in comparison to wildtype mice. The use of different angiotensin receptor
antagonists provided the in vitro evidence for a functional interaction between the Mas-
protooncogene and the AT1 receptor (von Bohlen und Halbach et al. 2000). Consequently,
the AT1-Mas complex could be of great importance as a target for pharmacological
intervention in cardiovascular diseases. Our experiments also revealed that both NO and
COX-2 are involved in the mediation of angiotensin 1-7-induced effect on LA-LTP (Albrecht
2007).
In summary, based on the enhanced cognitive performance mediated by ACE inhibitors
(see for review von Bohlen und Halbach and Albrecht 2006), capable of crossing the blood-
brain barrier, manipulation of the CNS angiotensin system might be considered as a novel
therapeutic target in the treatment of cognitive dysfunctions.
IX.
C
ONCLUSION
The present paper has presented a review of the current status of our knowledge of the
mechanisms of plasticity changes in the lateral amygdala. Though this knowledge is still
fragmentary, much more is known about the neuroscience of Pavlovian conditioning than
about any other form of learning and memory. We show that most of the mechanisms
responsible for plasticity changes in the LA have great similarities with that of CA1 region of
the hippocampus, including the main mechanisms of induction and persistence of LA-LTP
and LA-LTD. Therefore, we cannot agree with the generalized statement that, concerning the
synaptic plasticity and synaptic physiology, the amygdala is not the hippocampus (Chapman
2001). This conclusion was mainly based on the experiments done by Li et al. (2001). These
authors have shown that LFS of EC afferents to basolateral amygdala neurons results in
enduring enhancement of excitatory synaptic responses. The induction of this form of
synaptic plasticity was eliminated by one of the selective antagonists of kainate GLU
K5
receptors and could be mimicked by the GLU
K5
agonist ATPA. As described above
,
the level
of GLU
K5
receptors is higher in the amygdala than that in the hippocampus. A LFS-induced
enhancement of excitatory synaptic responses in the LA can be only obtained when very high
concentrations of ATPA (10 µM) are used. In drug-free control slices
,
LFS of EC fibers did
not provoke LTP-like changes in EPSP amplitude in our experiments. However, as shown
recently (Huang and Kandel 2007b; Huang and Kandel 2007a) we often observed a late
(about 50 min after LFS), long-lasting facilitation lasting >5 h in slice recordings.
The forthcoming
years will undoubtedly bring further clarification to diverse LTP and
LTD mechanisms in the amygdala and will allow getting more insight in the mode how they
contribute to adaptive brain function. Understanding the synaptic adaptations elicited and
regulated by different transmitter systems will not only provide mechanistic information
about how neural circuit modifications mediate experience-dependent plasticity but also will
