Spatio-temporal activation of cyclic AMP response element-binding protein, activity-regulated cytoskeletal-associated protein and brain-derived nerve growth factor: a mechanism for pontine-wave generator activation-dependent two-way active-avoidance memory processing in the rat.
The present study explored possible physiological and molecular mechanisms of pontine-wave (P-wave) generator activation-dependent memory processing in the rat using a two-way active-avoidance learning paradigm. The results show that learning training increased rapid eye movement sleep and activated brainstem cells in the P-wave generator. During this period, there was a time-dependent increase in phosphorylation of cAMP response element-binding protein (CREB) in the dorsal hippocampus and amygdala and increased synthesis of activity-regulated cytoskeletal-associated protein (Arc) in the dorsal hippocampus, amygdala, frontal cortex and occipital cortex. Learning training also increased synthesis of brain-derived nerve growth factor (BDNF) in the occipital cortex, amygdala and dorsal hippocampus at different time intervals. During this time, the levels of nerve growth factor did not change. The results also show that the increase in rapid eye movement sleep P-wave density during the post-training 3-h recording session is positively correlated with the increased levels of phosphorylated CREB, BDNF and Arc in the dorsal hippocampus. These results suggest that memory processing of two-way active-avoidance learning may involve excitation of P-wave-generating cells in the brainstem and increased expression of phosphorylated CREB, Arc and BDNF in a time-dependent manner in the forebrain. These dynamic changes in cellular and molecular features provide considerable insight into the mechanisms of the P-wave generator activation-dependent memory consolidation process.
Ulloor
Jagadish
J
Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Datta
Subimal
S
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D003598:Cytoskeletal Proteins; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004585:Electrooculography; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010766:Phosphorylation; D011149:Pons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D020932:Nerve Growth Factor