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.