The Journal of Neuroscience, June 22, 2005, 25(25):5894-5902; doi:10.1523/JNEUROSCI.0502-05.2005
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Cellular/Molecular
Encoding and Decoding of Dendritic Excitation during Active States in Pyramidal Neurons
Stephen R. Williams
Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
Neocortical neurons spontaneously fire action potentials during active network states; how are dendritic synaptic inputs integrated into the ongoing action potential output pattern of neurons? Here, the efficacy of barrages of simulated EPSPs generated at known dendritic sites on the rate and pattern of ongoing action potential firing is determined using multisite whole-cell recording techniques from rat layer 5 neocortical pyramidal neurons in vitro. Under quiescent conditions, the somatic impact of proximal (253 ± 15 µm from soma; n = 28) dendritic barrages of simulated EPSPs was 4.7-fold greater than identical barrages of EPSPs generated from distal (572 ± 13 µm from soma) sites. In contrast, barrages of proximal simulated EPSPs enhanced the rate of ongoing action potential firing, evoked by somatic simulated EPSPs, by only 1.6-fold more than distal simulated EPSPs. This relationship was apparent across a wide frequency range of action potential firing (6-22 Hz) and dendritic excitation (100-500 Hz). The efficacy of distal dendritic EPSPs was formed by the recruitment of active dendritic processes that transformed the ongoing action potential firing pattern, promoting action potential burst firing. Paired recordings (n = 42) revealed that patterns of action potential firing generated by concerted somatic and distal dendritic excitation reliably and powerfully drove postsynaptic excitation as a result of enhanced reliability of transmitter release during bursts of action potential firing. During active states, therefore, distal excitatory synaptic inputs decisively control the excitatory synaptic output of layer 5 neocortical pyramidal neurons and so powerfully influence network activity in the neocortex.
Key words: EPSP; action potential; neocortex; dendrite; sodium channel; HCN channel
Received Feb 7, 2005;
revised May 17, 2005;
accepted May 17, 2005.
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