Defective hippocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice

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.