Understanding the molecular and cellular mechanisms
underlying learning and memory is one of the most exciting topics in
the field of Neuroscience. Learning is thought to occur through
activity-dependent synaptic modification in the neuronal network. The
hippocampus, is an excellent structure to study synaptic plasticity
and learning, because of its anatomy and network. Most of the studies
in this thesis were performed on the hippocampus to unravel the
molecular and cellular mechanisms underlying spatial learning.
Molecular and cellular studies of mechanisms underlying mammalian
learning and memory have focused almost exclusively on postsynaptic
function. However, in chapter 2 we reveal a presynaptic mechanism
that modulates learning and synaptic plasticity in mice. Using
transgenic mice expressing a constitutively active form of H-ras (H-
rasG12V), we studied the H-Ras/ERK/Syn I pathway and showed that in
these mice ERK-dependent phosphorylation of synansin I is increased
and causes several presynaptic changes.
Calcium-calmodulin dependent protein kinase II (CaMKII) is a protein
kinase, which detects Ca2+ signals and can phosphorylate many target
proteins as well as itself. This auto-phosphorylation is critical for
its role in LTP and learning. However, in chapter 3 we show that
although CaMKII is required for normal presynaptic function, its
ability to phospho
