Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons. Issue 4 (1st August 2018)

• Record Type: Journal Article
• Authors: Müller, Peter; Draguhn, Andreas; Egorov, Alexei V.
• Is Part Of: Journal of neurochemistry. Volume 146:Issue 4(2018)
• Page Start: 446
• Page End: 458
• Publication Date: 2018-08-01
• Subjects: axon -- ectopic action potential -- hippocampal slice -- persistent sodium current -- phenytoin -- riluzole; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14479
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Axonal excitability is an important determinant for the accuracy, direction, and velocity of neuronal signaling. The mechanisms underlying spike generation in the axonal initial segment and transmitter release from presynaptic terminals have been intensely studied and revealed a role for several specific ionic conductances, including the persistent sodium current (IN aP ). Recent evidence indicates that action potentials can also be generated at remote locations along the axonal fiber, giving rise to ectopic action potentials during physiological states (e.g., fast network oscillations) or in pathological situations (e.g., following demyelination). Here, we investigated how ectopic axonal excitability of mouse hippocampal CA1 pyramidal neurons is regulated by IN aP . Recordings of field potentials and intracellular voltage in brain slices revealed that electrically evoked antidromic spikes were readily suppressed by two different blockers of IN aP, riluzole and phenytoin. The effect was mediated by a reduction of the probability of ectopic spike generation while latency was unaffected. Interestingly, the contribution of IN aP to excitability was much more pronounced in axonal branches heading toward the entorhinal cortex compared with the opposite fiber direction toward fimbria. Thus, excitability of distal CA1 pyramidal cell axons is affected by persistent sodium currents in a direction‐selective manner. This mechanism may be of importance for ectopic spike generation in oscillating network states as well as in pathological situations. Abstract : The excitability of axons determines timing and reliability of neuronal signaling. The underlying mechanisms are incompletely understood. Here, we show that blocking the persistent sodium current (IN aP ) with riluzole reduces the probability of spike generation in axons of mouse hippocampal CA1 pyramidal neurons. Population spikes were stronger affected in fibers heading toward the entorhinal cortex than to the fimbria, showing an asymmetric regulation of axonal excitability.