Although action potential initiation and propagation are essential to neuronal function, the small size of central neuron axons and collaterals have precluded direct characterization of these properties with traditional electrode recordings. Optical techniques for tracking membrane potential transients show immense promise for overcoming the low spatial resolution of patch electrode recording; however, low sensitivity previously prevented applying these techniques to questions related to phenomena too rapid or too complex to be studied by signal averaging. A recent enhancement in single cell voltage-sensitive dye (VSD) imaging enables high signal-to-noise, single-trial recordings from axons and axon collaterals with fine spatial (1–4 µm) and temporal (50–100 µs) resolution. Using this technique, we directly measured the spatio-temporal patterns of action potential initiation and propagation of cerebellar Purkinje neurons and layer 5 cortical pyramidal neurons, the principal output neurons of these structures. First, we found that action potentials in these neurons initiate in the axon initial segment and propagate in a saltatory manner. Secondly, with the exception of short-delay complex spikelets, which frequently died prior the first node, action potentials propagated reliably throughout all branches of local axonal arbors for physiologically relevant firing frequencies, 1 to 500 Hz. Furthermore, by combining single-cell VSD with pharmacological manipulations, we discovered that Kv1 subunit containing ion channels are important for repolarizing action potentials in cortical pyramidal axon collaterals and en passant presynaptic terminals. Finally, somatic depolarization of layer 5 pyramidal neurons elicited action potential broadening in collaterals and boutons in a distance dependent fashion. Moreover, this effect was blocked with Kv1 antagonists, indicating that D-current could play an important role in local circuit analog signal transmission. These findings mark significant advancements in our understanding of the relationship between morphology, signal integration, and propagation of action potentials in CNS axonal arbors.
|Advisor:||McCormick, David A.|
|School Location:||United States -- Connecticut|
|Source:||DAI-B 73/12(E), Dissertation Abstracts International|
|Keywords:||Action potential, Axon, Ion channels, Neuron axonal arbors, Voltage-sensitive dyes|
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