NMDA spikes in basal dendrites of cortical pyramidal neurons

Abstract

Basal dendrites are a major target for synaptic inputs innervating cortical pyramidal neurons. At present little is known about signal processing in these fine dendrites. Here we show that coactivation of clustered neighbouring basal inputs initiated local dendritic spikes, which resulted in a 5.9 +/- 1.5 mV (peak) and 64.4 +/- 19.8 ms (half-width) cable-filtered voltage change at the soma that amplified the somatic voltage response by 226 +/- 46%. These spikes were accompanied by large calcium transients restricted to the activated dendritic segment. In contrast to conventional sodium or calcium spikes, these spikes were mediated mostly by NMDA (N-methyl-D-aspartate) receptor channels, which contributed at least 80% of the total charge. The ionic mechanism of these NMDA spikes may allow 'dynamic spike-initiation zones', set by the spatial distribution of glutamate pre-bound to NMDA receptors, which in turn would depend on recent and ongoing activity in the cortical network. In addition, NMDA spikes may serve as a powerful mechanism for modification of the cortical network by inducing long-term strengthening of co-activated neighbouring inputs.

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

“…Basal spiny dendrites of neocortical pyramidal neurons exhibit regenerative Ca 2+ spikes mediated by NMDARs (Schiller et al, 2000), which could contribute to the observed Ca 2+ signals during coincident EPSP-bAP trains described here [in addition to the recently described spikes in radial oblique dendrites of CA1 neurons by Losonczy and Magee (2006), see above]. In addition, BDNF rapidly enhances NMDA-induced currents in cultured hippocampal neurons, primarily through receptors containing NR2B subunits (Levine and Kolb, 2000).…”

Initiation of Sodium Spikelets in Basal Dendrites of Neocortical Pyramidal Neurons

“…Recently, Ariav et al, (2003) used calcium imaging to determine the origin of fast spikes in CA1 hippocampal neurons. It is well known that the slow component of the synapticallyevoked or glutamate-evoked transient causes strong calcium elevations in thin dendritic branches of neocortical (Schiller et al, 2000) and hippocampal pyramidal neurons (Regehr & Tank, 1990;Wei et al, 2001). Calcium ions stream into the dendritic cytosol through either NMDA receptor channels (Schiller et al, 2000), voltage-gated calcium channels (VGCC) (Oakley, Schwindt & Crill, 2001a;Wei et al, 2001), or both, NMDA and VGCC channels.…”

“…It is well known that the slow component of the synapticallyevoked or glutamate-evoked transient causes strong calcium elevations in thin dendritic branches of neocortical (Schiller et al, 2000) and hippocampal pyramidal neurons (Regehr & Tank, 1990;Wei et al, 2001). Calcium ions stream into the dendritic cytosol through either NMDA receptor channels (Schiller et al, 2000), voltage-gated calcium channels (VGCC) (Oakley, Schwindt & Crill, 2001a;Wei et al, 2001), or both, NMDA and VGCC channels. Because fast spikes were always accompanied by a slow component, the calcium imaging data by Ariav et al, (2003) cannot be used to determine the site of origin, or to describe any other characteristics of fast spikes in the dendrites.…”

“…Local glutamate stimulation was used in earlier studies of basal function (Schiller et al, 2000;Oakley, Schwindt & Crill, 2001b), but fast spikes were not previously detected in basal dendrites of neocortical pyramidal cells. Recently, Ariav et al, (2003) used calcium imaging to determine the origin of fast spikes in CA1 hippocampal neurons.…”

Complexity of calcium signaling in synaptic spines

“…Note that Sjö strö m and colleagues were able to induce LTP with low frequency pairing when the soma was mildly depolarized. (34) Although the chemical consequences at the synapse remain unknown, it is tempting to imagine that this depolarization leads to calcium spikes in dendritic branchlets, (87,88) such that the frequency-dependence of CaM activation is dramatically altered by an additional mode of Ca 2þ entry. Future direction Clearly, this model does yet not explain the differences between the intracellular Ca 2þ dynamics required for the induction of LTP and LTD, or the critical time-window of STDP.…”