Firing mode-dependent synaptic plasticity in rat neocortical pyramidal neurons.

Pyramidal cells in the mammalian neocortex can emit action potentials either as series of individual spikes or as distinct clusters of high-frequency bursts. However, why two different firing modes exist is largely unknown. In this study, we report that in layer V pyramidal cells of the rat somatosensory cortex, in vitro associations of EPSPs with spike bursts delayed by +10 msec led to long-term synaptic depression (LTD), whereas pairings with individual action potentials at the same delay induced long-term potentiation. EPSPs were evoked extracellularly in layer II-III and recorded intracellularly in layer V neurons with the whole-cell or nystatin-based perforated patch-clamp technique. Bursts were evoked with brief somatic current injections, resulting in three to four action potentials with interspike frequencies of approximately 200 Hz, characteristic of intrinsic burst firing. Burst-firing-associated LTD (Burst-LTD) was robust over a wide range of intervals between -100 and +200 msec, and depression was maximal (approximately 50%) for closely spaced presynaptic and postsynaptic events. Burst-LTD was associative and required concomitant activation of low voltage-activated calcium currents and metabotropic glutamate receptors. Conversely, burst-LTD was resistant to blockade of NMDA receptors or inhibitory synaptic potentials. Burst-LTD was also inducible at already potentiated synapses. We conclude that intrinsic burst firing represents a signal for resetting excitatory synaptic weights.