Biology Reference
In-Depth Information
fear conditioning (Rodrigues et al. 2001), mutant mice lacking NR2A exhibit normal
responses to tone-dependent, hippocampal-independent fear response (Kiyama et al. 1998).
Synapses in the LA contain receptors composed of both NR2A and NR2B subunits (Sah
and Lopez 2003). It has been shown that LA-LTP is dependent on NR2B subunits, since the
selective antagonist ifenprodil impaired tetanus-induced LTP at thalamic input synapses
(Bauer et al. 2002). Using
different NMDA subunit antagonists (NVP-AAM 077, Co 101244,
Ro 04-5595), we have demonstrated in horizontal slices derived from adult mice that NR2B
and
NR2A subunits are involved in LA-LTP at cortical input synapses and that LA-LTD is
dependent on NR2B and to a lesser extent on NR2A subunits (unpublished observations).
In horizontal slices, EC-induced LA-LTP was also dependent on L-type voltage-gated
calcium channels (Drephal et al. 2006), whereas LA-LTP induced by stimulation of fibers
within the LA was not altered by the L-type calcium antagonist nifedipine. These results
support data obtained in coronal slices indicating that plasticity changes in the amygdala
show input-specific properties.
By application of the glutamate antagonist APV we showed for the first time that NMDA
receptors are required for the LFS-induced LTD in the LA (Kaschel et al. 2004). In addition,
our group (Kaschel et al. 2004) and others (Heinbockel and Pape 2000) could show that LA-
LTD is dependent on group II mGluRs in both, horizontal and coronal brain slices.
In coronal slices an involvement of VGCCs in spike-timing dependent LA-LTD has been
suggested (Humeau et al. 2005). Using in horizontal slices we were able to demonstrate that
L-type calcium channels are involved in the mechanisms of LFS-induced LTD-induction,
since nifedipine nearly completely blocks the intranuclear-induced LA-LTD (Tchekalarova
and Albrecht 2007).
Comparable results were obtained in the CA1 region of the hippocampus. Induction of
homosynaptic LTD depends on postsynaptic increases in calcium (Bear and Abraham 1996;
Bear and Malenka 1994; Kerr and Abraham 1996) brought about by different mechanisms
that include activation of NMDA receptors (Abraham and Wickens 1991; Mulkey and
Malenka 1992) or mGlu receptors (Oliet et al. 1997) Similarly, LFS of the LA induces two
distinct forms of LTD in the BLA, which depend either on the Ca
2+
influx through NMDARs
(Wang and Gean 1999) or on the activation of mGluRs (Lin et al. 2000). Concerning the
BLA, it has been also shown that a preconditioning HFS operating via activation of group II
mGluR altered the response to LFS from the induction of NMDAR-dependent LTP to LTD
(Li et al. 1998). These data represent an example of metaplasticity in the amygdala, since the
induction of synaptic plasticity could be modulated by previous/preconditioning synaptic
activity.
It has been evidenced that metabotrop glutamate 5 receptors (mGLUR5) are localized to
dendritic shafts and spines in the LA and are postsynaptic to auditory thalamic inputs
(Rodrigues et al. 2002). In the thalamo-amygdala pathway mGluR5 are involved in LA-LTP
induction (Rodrigues et al. 2002) besides NMDA receptors and L-type calcium channels,
whereas the mGluR1 antagonist CPCCOEt failed to show any effects on LA-LTP induction
(Lee et al. 2002). In a similar approach induction of LA-TP but not synaptic transmission was
disrupted by the mGLUR5 receptor antagonist MPEP (Fendt and Schmid 2002).
