Debate has raged over the last few years as to whether
cortical neurons transmit information primarily in their
average firing rates or in the precise timing of their
spikes. I will address the related question of which features
of spike trains control plasticity at cortical synapses.
Using paired recording in slices we have developed a
quantitative and predictive description of the joint dependence
of cortical plasticity on the rate and relative timing
of pre- and postsynaptic firing. The results hold important
implications for which parts of the neural code are most
readily stored for later retrieval. In addition, we have
examined the complimentary question of how plasticity
changes the coding properties of cortical synapses. Prior
work suggested that LTP in neocortex acts mainly by changing
short-term plasticity, which changes the way cortical
spike trains are read out by their postsynaptic targets.
In contrast, work in the hippocampus suggests that LTP
affects mainly the gain of transmission, without altering
synaptic dynamics. We find that neocortical LTP has mixed
effects, altering both short-term plasticity and the overall
gain of transmission. In contrast, LTD has essentially
pure effects on response dynamics. Finally, we have identified
the signaling pathways required for induction of spike-timing-dependent
LTD. Surprisingly, this form of plasticity appears to
require retrograde signaling by endogenous cannabinoids.
Not only do blockers of cannabinoid receptors block LTD,
but agonists at these receptors induce LTD when paired
with presynaptic activity. The requirement for presynaptic
activity is due to activation of presynaptic NMDA receptors
since activity dependent LTD induced by cannabinoid agonists
is still NMDA-dependent. Our experiments suggest a model
in which the coincident activation of presynaptic CB1
and NMDA receptors leads to a reduction in subsequent
transmitter release.
