Phosphorylation of CREB and DARPP-32 during late LTP at hippocampal to prefrontal cortex synapses in vivo.
Specific patterns of stimulation applied in the ventral hippocampus produce long-term potentiation (LTP) of postsynaptic synapses in the prefrontal cortex in vivo. The induction of LTP is dependent on NMDA receptors and cAMP-dependant kinase (PKA) activation. Yet little is known concerning the cellular mechanisms underlying the expression of this neocortical form of LTP. In the present study, we tested whether LTP at hippocampal to prefrontal cortex synapses leads to activation of DARPP-32 and CREB as well as defined the temporal regulation of the phosphorylation states of both proteins. Our data indicate a peak in CREB and DARPP-32 phosphorylation during the late phase of prefrontal LTP (2 h posttetanus). These findings support the hypothesis that prolonged expression of hippocampal-prefrontal cortex LTP depends on a synergistic mechanism involving phosphorylation of both CREB and DARPP-32 via activation of the cAMP/PKA-dependent pathway.
Hotte
Maïté
M
INSERM, U796, Pathophysiology of Psychiatric Disorders, University Paris Descartes, Faculty of Medecine Paris Descartes, 2ter rue d'Alésia, Paris F-75014, France.
Thuault
Sébastien
S
Dineley
Kelly T
KT
Hemmings
Hugh C
HC
Nairn
Angus C
AC
Jay
Thérèse M
TM
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32