Reduction in Neural Performance following Recovery from Anoxic Stress Is Mimicked by AMPK Pathway Activation

Abstract

Nervous systems are energetically expensive to operate and maintain. Both synaptic and action potential signalling require a significant investment to maintain ion homeostasis. We have investigated the tuning of neural performance following a brief period of anoxia in a well-characterized visual pathway in the locust, the LGMD/DCMD looming motion-sensitive circuit. We hypothesised that the energetic cost of signalling can be dynamically modified by cellular mechanisms in response to metabolic stress. We examined whether recovery from anoxia resulted in a decrease in excitability of the electrophysiological properties in the DCMD neuron. We further examined the effect of these modifications on behavioural output. We show that recovery from anoxia affects metabolic rate, flight steering behaviour, and action potential properties. The effects of anoxia on action potentials can be mimicked by activation of the AMPK metabolic pathway. We suggest this is evidence of a coordinated cellular mechanism to reduce neural energetic demand following an anoxic stress. Together, this represents a dynamically-regulated means to link the energetic demands of neural signaling with the environmental constraints faced by the whole animal.

Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon

“…) that should increase excitability, which conflicts with the DCMD's decreased excitability during hypoxia (Money et al. ). It is possible the persistent sodium currents are more tightly regulated in the DCMD given that it can fully recover from anoxia, whereas hippocampal and cardiac tissue experience cell injury and death.…”

“…After anoxic stress, the DCMD axon conducts fewer and slower high‐frequency APs (Money et al. ). However, under hypoxic conditions, persistent sodium currents increase in hippocampal (Hammarstrom and Gage ) and cardiac tissue (Ju et al.…”

“…) and may account for the DCMD's recovery of CV from hypoxia after application of adenylate cyclase activator (Money et al. ).…”

“…Our model supports both functions for the persistent and resurgent sodium current and suggests a possible mechanism to decrease expensive, high-frequency signaling that occurs in the DCMD after metabolic stress. After anoxic stress, the DCMD axon conducts fewer and slower high-frequency APs (Money et al 2014). However, under hypoxic conditions, persistent sodium currents increase in hippocampal (Hammarstrom and Gage 2000) and cardiac tissue (Ju et al 1996) that should increase excitability, which conflicts with the DCMD's decreased excitability during hypoxia (Money et al 2014).…”

“…After anoxic stress, the DCMD axon conducts fewer and slower high-frequency APs (Money et al 2014). However, under hypoxic conditions, persistent sodium currents increase in hippocampal (Hammarstrom and Gage 2000) and cardiac tissue (Ju et al 1996) that should increase excitability, which conflicts with the DCMD's decreased excitability during hypoxia (Money et al 2014). It is possible the persistent sodium currents are more tightly regulated in the DCMD given that it can fully recover from anoxia, whereas hippocampal and cardiac tissue experience cell injury and death.…”