Layer-specific NO dependence of long-term potentiation and biased NO release in layer V in the rat auditory cortex

1. We investigated the role of nitric oxide (NO) in the induction of long-t erm potentiation (LTP) in slices prepared from the rat auditory cortex. 2. Tetanic stimulation of layer IV elicited LTP of field potentials in laye r II-III (LTPII-III) and in layer V (LTPV). The magnitude of LTPII-III meas ured at 30 min after tetanic stimulation was 171 +/- 9 % (n = 15, mean +/- S.E.M.) Of the control measured before tetanic stimulation, while that of L TP, was 138 +/- 3 % (n = 17). 3. NO synthase (NOS) inhibitors had no apparent effect on LTPII-III, but LT P, was significantly suppressed (P < 0.001). This suppression of LTP, was s ignificantly antagonized by a NO donor (P < 0.001) or a cGMP analogue (P < 0.001). 4. Small non-pyramidal neurones in the auditory cortex were stained viith a n anti-neuronal NOX antibody. More neurones were stained with the antibody in the deeper cortical layers. 5. We measured neocortical NO release with electrochemical NO probes. Layer IV stimulation elicited significantly more NO release in layer V than in l ayer II-III (P < 0.001). The amplitude of the increase in NO concentration elicited by stimulation at 20 Hz for 5 s was 380 +/- 14 pM (n = 55) in laye r V and 55 +/- 8 pM (n = 5) in layer II-III. 6. NO release in layer V was partially but significantly suppressed by non- NMDA (P < 0.002) or NMDA (P < 0.002) receptor antagonists. Simultaneous app lication of the antagonists of the two types blocked NO release almost comp letely. 7. These results clearly indicate the NO dependence of the induction of LTP V, and the greater NO release in the deeper layer of the rat auditory corte x.