Metabolic cost of neuronal activity

• Applicant: Privatdozent Dr. Lars Kunz
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413134986

• Final Report Year: 2023

Final Report Abstract

Neuronal metabolism is of great interest, because the brain uses a substantial fraction of the body’s energy. However, the relation between ATP need and electrical activity is studied for only some brain regions. We chose auditory brainstem nuclei for mainly two reasons: (1) they represent biophysical extremes as prerequisite for their physiological functions; (2) they harbour only one major neuron type allowing for a simple correlation. We have studied the medial nucleus of the trapezoid body (MNTB), which represents a central hub in the auditory pathway faithfully transmitting signals over a wide range of firing frequencies. We compared the MNTB to the lateral superior olive (LSO), another auditory nucleus. LSO neurons exhibit a similarly broad range of firing frequencies and a very low membrane resistance. In our main project, we studied the metabolic adaptation of MNTB neurons to their broad firing frequency range. We monitored NADH and FAD by autofluorescence imaging and O2 concentrations in acute brainstem slices of the Mongolian gerbil (Meriones unguiculatus). When studying short-term metabolic changes in response to electrical activity, we found that oxidative phosphorylation (OxPhos) represents a major pathway for ATP generation in MNTB neurons. However, with increasing firing frequency, other metabolic pathways become important. Such a finding is relevant to the interpretation of functional neuroimaging that is often based upon changes in O2 levels. We studied metabolic responses not only during electrical activity, but also in quiet periods without firing. This is important, since our calculations of ATP consumption have clearly shown that auditory neurons use by far more ATP for maintaining their resting membrane potential than for firing. We found that the energetically demanding auditory brainstem nuclei showed different reactions to removing glucose. This points at nucleus specific specialities in neuronal metabolism – a finding important for the interpretation of functional neuroimaging. In both nuclei, lactate supplementation can rescue from glucose deprivation; with a stronger effect in the LSO. This supports the idea of lactate as brain nutrient in auditory neurons. As metabolic responses have shown to be very complex, we have developed a computational model of neuronal metabolism taking into account the biophysical specialities of auditory neurons. This model could describe metabolism both in quiescence and during stimulated activity and will substantially contribute to a better understanding and planning of future metabolic experiments. We suggest that our data are not only relevant for the interpretation of functional brain imaging data, but also for various neuropathologies with metabolic aspect.

Publications

• Relationship between oxygen consumption and neuronal activity in a defined neural circuit. BMC Biology, 18(1).
  Özugur, Suzan; Kunz, Lars & Straka, Hans
  
• Green oxygen power plants in the brain rescue neuronal activity. iScience, 24(10), 103158.
  Özugur, Suzan; Chávez, Myra N.; Sanchez-Gonzalez, Rosario; Kunz, Lars; Nickelsen, Jörg & Straka, Hans
  
• Transcardial injection and vascular distribution of microalgae in Xenopus laevis as means to supply the brain with photosynthetic oxygen. STAR Protocols, 3(2), 101250.
  Özugur, Suzan; Chávez, Myra N.; Sanchez-Gonzalez, Rosario; Kunz, Lars; Nickelsen, Jörg & Straka, Hans