P.J. Sjöström*, G.G. Turrigiano, and S.B. Nelson
Department of Biology and Volen Center for Complex Systems, 415 South Street, Waltham, MA 02454-9110
Prior studies in neocortical layer-5 (L5) pyramidal pairs found changes in short-term depression (STD) on induction of LTP or LTD, consistent with presynaptic expression. Here, we examine LTP in visual cortical L5 pairs.
Strong pre- and postsynaptic depolarizations (200 ms, 0.5-1.8 nA) reliably induced LTP (162±7.4%, n=31; p<0.01). STD increased in 17 of 31 pairs, suggesting LTP was not always presynaptic. Similarly, analysis of the coefficient of variation (CV) indicated presynaptic LTP in 12 pairs. Furthermore, the results of STD and CV analysis were correlated (r=0.70). LTP may thus be pre- and postsynaptic to varying degrees in individual pairs.
Nitric oxide (NO) is necessary for presynaptic LTP in several brain regions. We found LTP was reduced by the NO synthase blocker L-NAME (134±12%, n=8; p<0.05) and the membrane impermeable NO scavenger cPTIO (144±9.3%, n=6; p<0.05), and the remaining LTP was postsynaptic both by STD and CV analysis. Our results are consistent with the need for extracellular NO signalling in presynaptic, but not postsynaptic, LTP.
With high-frequency firing, presynaptic LTP may be partially masked by simultaneously induced LTD. In agreement, blockade of presynaptic LTD with the CB1 antagonist AM251 increased LTP (213±22%, n=9; p<0.01).
Probability of release (Prel) may saturate, suggesting presynaptic LTP may also saturate. In agreement, presynaptic LTP depended on paired-pulse facilitation (PPF, which is associated with Prel): Changes in PPF were correlated with initial PPF (r=-0.68), suggesting presynaptic LTP did not occur at synapses with maximized release.
Others have shown that PPF increases with age. We also found PPF and age were correlated (P12-P16; r=0.55). We investigated the possibility that presynaptic LTP is robust in old animals. Indeed, presynaptic LTP (assessed by the change in PPF) was obtained in slices from animals aged P15 or older (PPF after/before=-0.13±0.047, n=18), but not younger (0.0066±0.042, n=13; p<0.05). Interestingly, eyes open at P14, suggesting a link between plasticity and eye opening.