Defective hippocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice.
Mossy fiber long-term potentiation (mfLTP) was compared in hippocampal slices prepared from wild-type mice and mice lacking functional endothelial nitric oxide synthase (eNOS(-/-) mice) using field potential recording. In the presence of D-2-amino-5-phosphonovaleric acid (AP5, 50 microM), the mfLTP induced by tetanic stimulation (100 Hz, 1 sec) was significantly reduced in knockouts (n = 8) in comparison with wild-type (n = 8). Similarly, potentiation induced by forskolin (30 microM) or 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP, 100 microM) was less pronounced in knockouts. However, in wild-types the mfLTP-induced in the presence of the nonselective pharmacological inhibitor of NOS (N-nitro-L-Arginine, 100 microM, n = 6) was not significantly different from control (n = 8). Thus, eNOS is not directly involved in mfLTP, but lack of eNOS during development leads to a deficit downstream of adenylyl cyclase.
Doreulee
N
N
Institut für Neurophysiologie, Heinrich-Heine-Universität, D-40001 Düsseldorf, Germany.
Brown
R E
RE
Yanovsky
Y
Y
Gödecke
A
A
Schrader
J
J
Haas
H L
HL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005576:Colforsin; D019335:Nitroarginine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000262:Adenylyl Cyclases