Pre-synaptic terminal dynamics in the hippocampus

This thesis work dealt with the study of synaptic plasticity in the adult brain. This is an area of
intensive investigation because instability of synapses is believed to underlie cognitive
processes like learning and memory in the CNS, and adaptation to injury or paralysis in the
PNS.
Structural changes involving large-scale growth and retraction of neuronal processes or finetuning
of connections are well documented in the developing nervous system and are thought
to naturally decrease in mature systems. Evidence for post-synaptic structural changes in the
adult brain is numerous. In contrast, rearrangements of pre-synaptic terminals are much less
studied and we simply do not know their capacity for plastic changes.
To investigate these issues we generated mice expressing membrane- and/or synaptic vesicletargeted
spectral variants of GFP in neuronal subsets to image identified presynaptic terminals.
This unique tool allowed us, for the first time, to follow individual presynaptic terminals over
long periods of time by confocal and conventional time-lapse microscopy. Because of its
prominent role in learning and memory we have chosen the hippocampus as a model system.
The use of in vitro and ex vivo preparations (hippocampal slice culture and whole mount
preparations) enabled us to investigate the molecular mechanisms of pre-synaptic terminal
plasticity in the hippocampus. Our main findings are:
1) Pre-synaptic terminal numbers in mature hippocampal networks are in a state of dynamic
equilibrium. 2) Mature mossy fibers display short-term dynamic behaviors resembling those
typical during development. 3) Distinct types of terminals of the same neuron exhibit unique
dynamic properties. 4) Stable terminals can be reversibly converted into dynamic ones by
patterned electrical activity. 5) This process is mediated through AMPA-receptor activation,
PKA and protein synthesis. We conclude that stable presynaptic terminals in mature
hippocampal networks can be converted into dynamic ones by synaptic activity, demonstrating
regulated pre-synaptic rearrangements in these networks.
The usefulness of the targeted-GFP transgenic mice for many fields of neuroscience research
was also demonstrated in several additional experimental designs and applications.