Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area.
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength. Inhibition of the serine/threonine kinase Akt increased baseline γ oscillations and partially blocked its nicotinic enhancement. We propose that the PKA-NMDAR-PI3K-ERK pathway modifies cellular properties required for the nicotinic enhancement of γ oscillations, dependent on a PKC-ERK mediated pathway. These signaling pathways provide clues for restoring γ oscillations in pathological conditions affecting cognition. The suppression of γ oscillations at 100 μM nicotine was only dependent on PKA-NMDAR activation and may be due to very high intracellular calcium levels.
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical UniversityXinxinang, China; Department of Pathophysiology, Xinxiang Medical UniversityXinxinang, China.
JianGang
J
Wang
Key Laboratory of Neuronal Oscillation and Disease, Yantze University Medical School JingZhou, China.
XiaoLong
X
He
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical UniversityXinxinang, China; Department of Neurobiology and Physiology, Xinxiang Medical UniversityXinxinang, China.
Fangli
F
Guo
Department of Laboratory Medicine, Yantze University Affiliated Hospital JingZhou, China.
XiangLin
X
Cheng
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical UniversityXinxinang, China; Department of Neurobiology and Physiology, Xinxiang Medical UniversityXinxinang, China.
Yali
Y
Wang
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University Xinxinang, China.
XiaoFang
X
Wang
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University Xinxinang, China.
ZhiWei
Z
Feng
Department of Psychology, Xinxiang Medical UniversityXinxinang, China; School of Life Sciences, Birmingham City UniversityBirmingham, UK.
Martin
M
Vreugdenhil
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical UniversityXinxinang, China; Key Laboratory of Neuronal Oscillation and Disease, Yantze University Medical SchoolJingZhou, China; Department of Neurobiology and Physiology, Xinxiang Medical UniversityXinxinang, China.
ChengBiao
C
Lu
Akt; ERK1/2; PI3 kinase; PKA; PKC; hippocampus; nAChR; γ oscillations