The properties and implications of NMDA spikes in neocortical pyramidal cells

Integration of synaptic input in dendritic trees is a nonlinear process in which excitatory input may elicit spikes localized within the branch receiving input. In addition to membrane current-driven events, a type of dendritic spike has recently been described that instead depends on NMDA receptor current. These NMDA spikes enable superlinear integration among inputs targeted close together on a single branch. Here a compartment model of a layer 5 pyramidal cell was used to examine the mechanisms underlying NMDA spikes and to test properties not directly accessible experimentally. The results indicate the following: initiation of an NMDA spike in a tertiary dendrite in 1 mm [Mg2+] requires an NMDA conductance density equivalent to 6-8 nS within a 25-microm-long dendritic subsegment; dendritic membrane currents are not required for NMDA spike production; and targeted dendritic (but not somatic) inhibitory input is exquisitely suited to veto an NMDA spike if it arrives within a 30 ms window in time. Finally, an analysis of the spatial density of NMDA conductance required for NMDA spike production implies that, at least up to the age (postnatal day 35) that these events have been observed, most of the excitatory synaptic conductance arriving at pyramidal cells is NMDA mediated.