Activation of phasic pontine-wave generator in the rat: a mechanism for expression of plasticity-related genes and proteins in the dorsal hippocampus and amygdala.
A number of behavioral studies have emphasized the importance of interactions between the pontine-wave (P-wave) generator and the dorsal hippocampus (DH) in two-way active avoidance (TWAA) memory processing; however, the direct involvement of the P-wave generator in the TWAA training trial-induced molecular events in the DH and amygdala has not been systematically evaluated. Here we demonstrate that the TWAA learning training trials activate P-wave generator, and increase phosphorylation of CREB (pCREB) and expression of activity-regulated cytoskeletal-associated (Arc) protein, as well as messenger ribonucleic acid (mRNAs) of Arc, brain-derived nerve growth factor (BDNF) and early growth response-1 (Egr-1) in the DH and amygdala. Selective elimination of P-wave-generating cells abolished P-wave activity and suppressed TWAA learning training trial-induced expression of pCREB and Arc proteins and Arc, BDNF and Egr-1 mRNAs in the DH and amygdala. Following a session of TWAA training, all rats were equal in terms of time spent in wakefulness, slow-wave sleep and rapid eye movement (REM) sleep irrespective of P-wave lesions. The second set of experiments demonstrated that localized cholinergic stimulation of the P-wave generator increased expression of Arc, BDNF and Egr-1 mRNAs in the DH. Together, these findings provide the first direct evidence that activation of P-wave-generating cells is critically involved in the TWAA training trial-induced expression of plasticity-related genes in the DH and amygdala. These findings are discussed in relation to the role of P-wave generator activation for the REM sleep-dependent development and cognitive functions of the brain.
Datta
Subimal
S
Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. subimal@bu.edu
Li
Guangmu
G
Auerbach
Sanford
S
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D050882:CREB-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D011149:Pons / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D050882:CREB-Binding Protein