Presynaptic mechanisms determining the dynamic range of neurotransmitter release in the lateral amygdala

The amygdala is a central brain structure receiving sensory information from diverse regions
of the central nervous system. Cortical and thalamic axons converge to the lateral amygdala
(LA) which is thought to be the main site for fear-induced plasticity and associative learning.
Several years ago, a new form of presynaptic long-term potentiation (LTP) was identified at
the cortico-LA synapse. This heterosynaptic associative LTP (LTPHA) is triggered by the
activation of presynaptic NMDA receptors (NMDAR) at cortical presynaptic terminals, with
the request of thalamic activation. However, nothing was known so far on the molecular
mechanism involved. During my thesis, I could show that LTPHA is mediated by an increase
in the probability of vesicular release. Downstream to NMDAR opening, the activation of the
adenylyl cyclase (AC) / protein kinase A (PKA) pathway recruits the synaptic protein Rim1α.
The L-type voltage-dependent calcium channels (VDCCs) are also necessary for LTPHA
expression. The activation of PKA and the functional interaction between Rim1α and L-type
VDCCs appear to be essential for the expression of presynaptic LTP, but could also play a
role for baseline synaptic transmission in the amygdala.