Program & Abstract Book - EPFL Latsis Symposium 2009

EPFL Latsis Symposium 2009: Understanding Violence
P-22
76
February 11-13 2009
im p o r t a n c e o f cbp a n D torc1 in creb
t r a n s c r i p t i o n a l a c t i v a t i o n
Guidi, Raffaella1 2 ; Magistretti, Pierre J. 1 3 ; Halfon, Olivier2 ;
1 2
Cardinaux, Jean-René
1 Centre for Psychiatric Neuroscience, CHUV, Lausane; 2 Child and
Adolescent Psychiatry (SUPEA), Lausanne; 3 Brain Mind Institute,
EPFL, Lausanne
cAMP-response-element-binding protein (CREB) is a member of a family
of proteins that function as transcription factors. It is expressed in all cells
in the brain and its activation is known to play a crucial role in learning
and memory, as well as in several neuropsychiatric disorders. However,
depending on the brain region and the stimuli leading to its transcriptional
activation, neuronal functions may be affected in different manners. In
the context of addiction, CREB was shown to be critical. When CREB is
phosphorylated, it recruits a coactivator called CBP, and activates the expression
of a set of genes that modifies the properties of striatal medium
spiny neurons in the reward pathway. Moreover, we have recently shown
that another coactivator called Transducer Of Regulated CREB activity 1
(TORC1) functions as a calcium- and cAMP-sensitive coincidence detector
in neurons, and is involved in hippocampal long-term synaptic plasticity
(Kovacs et al., 2007.PNAS 104, 4700-4705). Given the importance of calcium
and cAMP signaling pathways for reward-related long-term memory
formation, we hypothesized that TORC1 could play a role in this process.
To determine the respective involvement of CBP and TORC1 in the regulation
of CREB-mediated transcription, we are developing different strategies
to selectively interfere with these CREB coactivators in mouse primary
neurons. Ultimately, we would like to better define the role of CREB, CBP
and TORC1 in reward-related learning and memory and drug addiction.