The CRE/CREB pathway is transiently expressed in thalamic circuit development and contributes to refinement of retinogeniculate axons

The development of precise connections in the mammalian brain proceeds thro ugh refinement of initially diffuse patterns, a process that occurs largely within critical developmental windows. To elucidate the molecular pathways that orchestrate these early periods of circuit remodeling, we have examin ed the role of a calcium- and cAMP-regulated transcriptional pathway. We sh ow that there is a window of CRE/CREB-mediated gene expression in the devel oping thalamus, which precedes neocortical expression. In the LGN, this wav e of gene expression occurs prior to visual experience, but requires retina l function. Mutant mice with reduced CREB expression show loss of refinemen t of retinogeniculate projections. These results suggest an important role of the CRE/CREB transcriptional pathway in the coordination of experience-i ndependent circuit remodeling during forebrain development.