Mossy fiber long-term potentiation (mfLTP) was compared in hippocampal slic
es prepared from wild-type mice and mice lacking functional endothelial nit
ric oxide synthase (eNOS(-/-) mice) using field potential recording. In the
presence of D-2-amino-5-phosphonovaleric acid (AP5, 50 muM), the mfLTP ind
uced by tetanic stimulation (100 Hz, 1 sec) was significantly reduced in kn
ockouts (n = 8) in comparison with wild-type (n = 8). Similarly, potentiati
on induced by forskolin (30 muM) or 8-bromo-cyclic adenosine monophosphate
(8-Br-cAMP, 100 muM) was less pronounced in knockouts. However, in wild-typ
es the mfLTP-induced in the presence of the nonselective pharmacological in
hibitor of NOS (N-nitro-L-Arginine, 100 muM, n = 6) was not significantly d
ifferent from control (n = 8). Thus, eNOS is not directly involved in mfLTP
, but lack of eNOS during development leads to a deficit downstream of aden
ylyl cyclase. Synapse 41:191-194,2001. (C) 2001 Wiley-Liss, Inc.