Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures

Abstract

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever‐like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature‐sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage‐sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10–30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after‐potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature‐sensitive conduction failures above, but not below, normal body temperature, and the failure‐reducing effect of the spike's depolarizing after‐potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions.

Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission

“…Since one axon serves all synapses in an autaptic neuron, the disruption of action potential propagation before reaching the first synapses results in the complete loss of eEPSCs. Interestingly, it was reported that warming cortical slices (42 °C), which makes membranes more liquid, similarly to cholesterol depletion, also results in action potential propagation failure 47 . The search for the mechanism of the disruption of action potential propagation in cholesterol-depleted axons exceeds the scope of this study.…”

Infrared inhibition and waveform modulation of action potentials in the crayfish motor axon

“…A previous study using squid giant axons demonstrated that changes in steady state bath temperature profoundly altered the AP duration and amplitude [33]. A recent study using unmyelinated axons in the rat cerebellum and hippocampus showed that raising bath temperature reduced or blocked CAPs [39]. In general, the AP amplitude and duration decreased when the bath temperature was raised.…”

The Slow Depolarization Following Individual Spikes in Thin, Unmyelinated Axons in Mammalian Cortex

“…In such experiments, a failure at the first stimulus increased the failure rate at the second stimulus (changed from 50% to 75% failures at 30 ms interval), suggesting a slightly reduced excitability after a single stimulus. In contrast, a success on the first stimulus almost eliminated failures at the second stimulus (<0.1% failures, Pekala et al, 2016). This means that the excitability-increasing effect of a spike in the tested unit's axon was much stronger than the influence from adjacent synchronously activated axons.…”

“…To summarize, increases in population propagation speed and amplitude are robustly demonstrated in whole animals (Gardner-Medwin, 1972), cerebellar and hippocampal slices (Wigström and Gustafsson, 1981), at temperatures between 22 and 35°C (Soleng et al, 2004; Pekala et al, 2016), and in peripheral cold-sensitive C-fibers and sympathetic axon in humans (Bostock et al, 2003).…”

“…One way to better understand the impact of such stimulation is to activate a bundle of axons and record the antidromic spike at the soma of only one of them. Then it is possible to find the axonal activation threshold of the recorded unit, obtaining both successful activations and failures with the same stimulation strength, while maintaining a relatively constant number of activated axons (Pekala et al, 2016). In such experiments, a failure at the first stimulus increased the failure rate at the second stimulus (changed from 50% to 75% failures at 30 ms interval), suggesting a slightly reduced excitability after a single stimulus.…”