Type: Response Essays
Sample donated: Annie Buchanan
Last updated: September 12, 2019
The brainhas high energy requirements and neuronal activity is associated with a remarkableincrease in metabolic activity. Synapses consume the majority of neuronal energy,but are located at considerable distance from the metabolic machinery in the cellbody. Local mechanisms must exist to sense increased synaptic activity andprovide appropriate energy substrates to the synapse.
Ashrafi et al. (2017) identify such a mechanism1. They reportthat synapses rely on the glucose transporter GLUT4 to meet the activity-drivenincrease in energy. Action potential firing triggers insertion of GLUT4 intothe presynaptic membrane, which increases the ability of the neuron to captureglucose and generate energy.
In contrast, ablation of GLUT4 leads to an arrestof presynaptic vesicle recycling and inhibition of synaptic transmission duringsustained action potential firing. This discovery demonstrates on demand neuronalmetabolism, to ensure accurate and continuous synaptic function. These recentfindings are of tremendous importance as they identify synapses as criticalsites of metabolic control and indicate that the energy supply for neurons canbe generated locally in neuronal compartments. Divakaruni et al. (2017) question the concept that neurons depend on glucosemetabolism and use glutamate only as a neurotransmitter2. Performing13C tracer analysis in neuronal cell culture and brain slices,Divakaruni et al. found that neurons could switch to glutamate oxidation as analternative to glucose.
Amongst other things, they reason that this metabolicmechanism protects against glutamate excitotoxicity. Glutamate is releasedspecifically from presynaptic terminals. This implies that the metabolicswitching is likely active within the presynaptic terminal.
I foundthese publications particularly exciting, as they progress our understanding ofthe metabolic mechanisms at synapses and their contribution to synaptictransmission in response to neuronal activity. Converging evidence indicates anassociation of neurodegenerative diseases with metabolic deficits. Furtherresearch concerning metabolic mechanisms in the different neuronal compartmentswill help us to gain a coherent view of brain energy metabolism. Ultimately, abetter understanding of these metabolic processes will help to tackle diseasemechanisms.