A fascinating aspect of the learning and memory process is its
biological basis. Both short- and long-term memories are thought to be
expressed by changes in the efficacy of synaptic transmission. In long-term
memory, these changes, which are associated with structural modifications
of synapses, depend on an initial and brief temporal phase during which
gene expression is essential (consolidation phase). This is a universal
feature of long-term memory processes, found in several different forms of
memory and conserved throughout evolution.
Which classes of genes are essential for the formation of long-term synaptic plasticity and which are important for the consolidation of long-term memory?
In the invertebrate system, Aplysia californica, I have identified a
regulatory immediate early gene which is essential for the consolidation
phase of long-term synaptic plasticity related to a simple form of
learning. In mammals, in contrast, far less is known about the genes
important for the formation of long-term memory and this is the main goal
of the lab. We are taking the following approaches to identify and
characterize genes critical in long-term synaptic plasticity and long-term
memory consolidation in the mammalian brain: 1) We are screening the
mammalian brain for homologues of the invertebrate genes which we already
know to be important in some forms of memory storage in Aplysia; 2) we hope
to identify molecules associated with long-term synaptic plasticity (in
vitro and in vivo) and with the establishment of long-term memory
(behavioral) in mammals by gene differential screenings and recombinant
gene expression.
C.M. Alberini, M. Ghirardi, R.Metz, E.R. Kandel. C\EBP is an
immediate early gene required for the consolidation of long-term
facilitation in Aplysia. Cell 76, 1099. 1994.
C.M. Alberini, M. Ghirardi, Y. Huang, P.V. Nguyen, E.R. Kandel. A
molecular switch for the consolidation of long-term memory: cAMP inducible
gene expression. Annals of the New York Acad. Sci. Vol. 758, 261. 1995.
The gene control region of a typical eucaryotic gene.
The promoter is the DNA sequence where the general transcription factors
and the polymerase assemble. The regulatory sequences serve as binding
sites for gene regulatory proteins, whose presence on the DNA affects the
rate of transcription initiation. We are now focusing on the
characterization of regulatory proteins that control gene expression in
long-term synaptic plasticity and long-term memory.