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V. G ENDER D IFFERENCES
Most of the studies in the amygdala neglected female rats . However, since hippocampal
LTP and fear conditioning is known to differ in males and females (Maren et al. 1994) we
were interested in getting insight in a possible gender-dependence of neuronal plasticity
within the LA. We were not able to demonstrate gender specific differences in HFS-induced
LA-LTP (Drephal et al. 2006) or in LFS-induced LA-LTD (Kaschel et al. 2004). However, in
agreement with data obtained in the dentate gyrus of urethane anesthetized rats (Maren et al.
1994; Maren 1995) we could demonstrate gender specific differences in LA-LTP magnitude
when TBS was applied (Drephal et al. 2006). The small, but significant higher magnitude of
TBS-induced LA-LTP in females in comparison to males was also found in the BLA when
TBS was applied to induce LTP (Krezel et al. 2001). It is known that TBS is more sensitive to
pharmacological manipulations and age-dependent factors than HFS (Diamond et al. 1996;
Hellner et al. 2005; Moore et al. 1993). It is further known that gonadal steroids have a
profound impact on the morphology of dendrites and patterns of synaptic connectivity (Cooke
and Woolley 2005; Pozzo-Miller et al. 1999; Romeo et al. 2005). Comparable to the results
obtained in the hippocampus, we have shown that the magnitude of LA-LTP depends on the
phase of the estrus cycle (Schubert et al. 2007). Additionally, we found gender-dependent
changes in the magnitude of LA-LTP after stimulation of kainate GLU K5 receptors by the
specific agonist ATPA.
Kainate receptors are hetero-oligomeric receptor channels composed of the subunits
glutamate receptor GLU K5 , GLU K6 , GLU K7 , GLU K1 and GLU K2 (Huettner 2003). They appear
to play a specific role in the regulation of synaptic network activity, such as mediation of
excitatory synaptic transmission (Clarke and Collingridge 2002; Li and Rogawski 1998) or
the modulation of neurotransmitter release (Braga et al. 2003; Frerking and Nicoll 2000).
GLU K5 kainate receptors are, compared to the hippocampus, highly expressed in the adult
amygdala (Bettler et al. 1990; Li et al. 2001). Low concentrations of ATPA reduced high-
frequency-induced LA-LTP in males, while it enhanced LTP in females during certain phases
of the estrus cycle. The ATPA-induced changes of LA-LTP could be blocked with the
specific GLU K5 kainate receptor antagonist UBP296. The gender-specific effects of ATPA on
LA-LTP could be due to the influences of sex hormones, which may alter GLU K5 receptor
expression or GLU K5 -induced currents. Thus, our results could be interpreted as molecular
and neurophysiological correlates of gender- and hormone-specific alterations in behavior and
functional memory, and may represent one explanation for gender differences seen in
epilepsy (Christensen et al. 2005). In addition, Mitsushima and co-authors have found sex
differences in the extracellular levels of serotonin and dopamine in the BLA and their
responses to restraint stress. For instance, the mean extracellular levels of serotonin or
dopamine in the BLA were higher in male than in female rats (Mitsushima et al. 2006). These
differences may not only contribute to the sex-specific emotional response at the behavioural
level, but also to sex-specific differences in mechanisms of learning and memory.
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