RT Journal Article
SR Electronic
T1 Bidirectional Regulation of the cAMP Response Element Binding Protein Encodes Spatial Map Alignment in Prism-Adapting Barn Owls
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9898
OP 9909
DO 10.1523/JNEUROSCI.1385-08.2008
VO 28
IS 40
A1 Grant S. Nichols
A1 William M. DeBello
YR 2008
UL http://www.jneurosci.org/content/28/40/9898.abstract
AB The barn owl midbrain contains mutually aligned maps of auditory and visual space. Throughout life, map alignment is maintained through the actions of an instructive signal that encodes the magnitude of auditory-visual mismatch. The intracellular signaling pathways activated by this signal are unknown. Here we tested the hypothesis that CREB (cAMP response element-binding protein) provides a cell-specific readout of instructive information. Owls were fitted with prismatic or control spectacles and provided rich auditory-visual experience: hunting live mice. CREB activation was analyzed within 30 min of hunting using phosphorylation state-specific CREB (pCREB) and CREB antibodies, confocal imaging, and immunofluorescence measurements at individual cell nuclei. In control owls or prism-adapted owls, which experience small instructive signals, the frequency distributions of pCREB/CREB values obtained for cell nuclei within the external nucleus of the inferior colliculus (ICX) were unimodal. In contrast, in owls adapting to prisms or readapting to normal conditions, the distributions were bimodal: certain cells had received a signal that positively regulated CREB and, by extension, transcription of CREB-dependent genes, whereas others received a signal that negatively regulated it. These changes were restricted to the subregion of the inferior colliculus that received optically displaced input, the rostral ICX, and were not evident in the caudal ICX or central nucleus. Finally, the topographic pattern of CREB regulation was patchy, not continuous, as expected from the actions of a topographically precise signal encoding discrete events. These results support a model in which the magnitude of CREB activation within individual cells provides a readout of the instructive signal that guides plasticity and learning.