GABA(B) receptor activation inhibits neuronal excitability and spatial learning in the entorhinal cortex by activating TREK-2 K+ channels.
The entorhinal cortex (EC) is regarded as the gateway to the hippocampus and thus is essential for learning and memory. Whereas the EC expresses a high density of GABA(B) receptors, the functions of these receptors in this region remain unexplored. Here, we examined the effects of GABA(B) receptor activation on neuronal excitability in the EC and spatial learning. Application of baclofen, a specific GABA(B) receptor agonist, inhibited significantly neuronal excitability in the EC. GABA(B) receptor-mediated inhibition in the EC was mediated via activating TREK-2, a type of two-pore domain K(+) channels, and required the functions of inhibitory G proteins and protein kinase A pathway. Depression of neuronal excitability in the EC underlies GABA(B) receptor-mediated inhibition of spatial learning as assessed by Morris water maze. Our study indicates that GABA(B) receptors exert a tight control over spatial learning by modulating neuronal excitability in the EC.
Deng
Pan-Yue
PY
Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
Xiao
Zhaoyang
Z
Yang
Chuanxiu
C
Rojanathammanee
Lalida
L
Grisanti
Laurel
L
Watt
John
J
Geiger
Jonathan D
JD
Liu
Rugao
R
Porter
James E
JE
Lei
Saobo
S
D054758:A Kinase Anchor Proteins / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods
D054758:A Kinase Anchor Proteins; C119530:AKAP3 protein, human; D018755:GABA Agonists; C503444:Kcnk10 protein, rat; D024683:Potassium Channels, Tandem Pore Domain; D018080:Receptors, GABA-B; D017868:Cyclic AMP-Dependent Protein Kinases; D001418:Baclofen