Bidirectional Regulation of the cAMP Response Element Binding Protein Encodes Spatial Map Alignment in Prism-Adapting Barn Owls

Abstract

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 minutes of hunting using phosphorylation state-specific (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 re-adapting 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, while others a signal that negatively regulated it. These changes were restricted to the sub-region of the inferior colliculus that received optically displaced input, the rostral ICX, and 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.

Auditory Processing, Plasticity, and Learning in the Barn Owl

“…These results support a model in which CREB provides a readout of instructive information (Nichols and DeBello 2008). While the specific gene products operating downstream of CREB are not known, transcriptome-wide analysis of actively adapting owls found downregulation of ubiquitin (Swofford and DeBello 2007), a key component of protein degradation machinery that has been implicated in activity-dependent synaptic turnover (Zhao et al 2003).…”

Endocannabinoid-Mediated Long-Term Depression in the Avian Midbrain Expressed Presynaptically and Postsynaptically

“…Furthermore, a recent report showed that cAMP response element binding protein (CREB), a downstream target of the cAMP/PKA pathway, is involved in remapping the inferior colliculus during prisminduced learning in barn owls (Nichols and DeBello, 2008). Our result that LTD at the CSh-EX synapse is mediated by a PKAdependent reduction of the NMDA/AMPA ratio is consistent with these findings.…”

Rapid and Widespread Effects of 17β-Estradiol on Intracellular Signaling in the Male Songbird Brain: A Seasonal Comparison

“…9198) for 24 h. Also, sections were incubated in secondary antibody for 18 h and DAB for 16 min. This pCREB antibody has been successfully used on avian brain (41), and zebra finch CREB mRNA is highly similar to mammalian CREB mRNA (42). This…”