Biology Reference
In-Depth Information
VII.
M
ODULATION OF THE
M
AGNITUDE OF
LA-LTP
U
NDER
S
PECIAL
C
ONSIDERATION OF
S
TRESS
-R
ELATED
N
EUROMODULATORS
In addition to the signaling pathways described above, LTP in the basolateral complex of
the amygdala can be modulated by a variety of molecules (Table 1). Behavioral experiments
have shown the involvement of additional transmitters in amygdala-mediated learning
mechanisms (Adamec 1997; Guterman and Richter-Levin 2006; Izquierdo et al. 1995;
Rattiner et al. 2005; Roozendaal et al. 2007).
Extensive evidence indicates that stress hormones may affect memory storage and
memory consolidation via noradrenergic mechanisms in the amygdala. Dopamine increases
the excitability of inhibitory interneurons in the LA. Using whole-cell recordings from LA
projection neurons in coronal mouse brain slices, it has been found that dopamine strongly
increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs). In addition,
dopamine application induced low-frequency (2-6 Hz) oscillatory activity of inhibitory
circuits in the absence of excitatory input. The increase in sIPSC frequency required
activation of D1-like receptors. Unlike D1 receptor-mediated transmission in other brain
areas, this effect was independent of the cAMP/PKA signal transduction cascade, but
involved activation of the protein tyrosine kinase Src (Guarraci et al. 1999). Dopamine
transmission within the amygdala contributes to the acquisition and expression of Pavlovian
fear conditioning (Inglis and Moghaddam 1999). In addition, dopaminergic innervation of the
amygdala may be more responsive to stress than other dopamine-innervated regions of the
limbic system
(e.g. the prefrontal cortex), implicating that amygdaloid dopamine in normal
and pathophysiological processes subserves an organism's response to stress (Johnson et al.
2005).
It is known that the LA is a region specifically implicated in the formation of memories
for stressful experiences. Recent findings suggest that endocannabinoid CB1 receptors in the
BLA contribute to stress-induced analgesia (Connell et al. 2006). In addition, using electron
microscopy, glucocorticoid receptors has been found localized to non-genomic sites in rat
lateral amygdala, glia processes, presynaptic terminals, neuronal dendrites, and dendritic
spines including spine organelles and postsynaptic membrane densities (Goussakov et al.
2006). By studying the effects of stress and corticosterone in vivo, it could be demonstrated
that the BLA mediates the effects of stress on memory-related processes. The design of such a
study can be the following: rats were exposed to an acute elevated-platform stress and
administered with vehicle or 5 mg/kg, 10 mg/kg, or 25 mg/kg of corticosterone systemically.
Thereafter, they were anesthetized and prepared for field potential recording in the BLA, in
response to stimulation of the entorhinal cortex. Using such an approach, it could be
demonstrated that the elevated platform stress enhanced baseline responses in BLA and
plasma corticosterone but inhibited amygdaloid LTP (Kavushansky and Richter-Levin 2006).
In contrast, predator stress enhanced LTP in BLA (Vouimba et al. 2006). Thus, many factors,
including the type of stress, the phase of the stress response, the type of LTP, and the life
history of the organism determine in which direction LTP will be changed. These results may
have consequences for the understanding of the posttraumatic stress disorder or of depression,
considering that posttraumatic stress disorder is the pathological replay of emotional memory
formed in response to painful, life-threatening, or horrifying events, whereas depression is
often precipitated by more social context-related stressors (Post et al. 1998).
