Abstract
The metabolism of glucose is a nearly exclusive source of energy for maintaining neuronal survival, synaptic transmission and information processing in the brain. Two glucose metabolism pathways have been reported, direct neuronal glucose uptake and the astrocyte-neuron lactate shuttle (ANLS), which can be involved in these functions simultaneously or separately. Although ANLS in the dorsal hippocampus (DH) has been proved to be required for memory consolidation, the specific metabolic pathway involved during memory acquisition remains unclear. The DH and amygdala are two key brain regions for acquisition of contextual fear conditioning (CFC). In 2-NBDG experiments, we observed that 2-NBDG-positive neurons were significantly increased during the acquisition of CFC in the DH. However, in the amygdala and cerebellum, 2-NBDG-positive neurons were not changed during CFC training. Strikingly, microinjection of a glucose transporter (GLUT) inhibitor into the DH decreased freezing values during CFC training and 1 h later, while injection of a monocarboxylate transporter (MCT) inhibitor into the amygdala also reduced freezing values. Therefore, we demonstrated that direct neuronal glucose uptake was the primary means of energy supply in the DH, while ANLS might supply energy in the amygdala during acquisition. Furthermore, knockdown of GLUT3 by a lentivirus in the DH impaired the acquisition of CFC. Taken together, the results indicated that there were two different glucose metabolism pathways in the DH and amygdala during acquisition of contextual fear memory and that direct neuronal glucose uptake in the DH may be regulated by GLUT3.
Highlights
It is well known that a highly active brain accounts for at least 20% of the body’s daily energy consumption
We found that direct neuronal glucose uptake was the primary energy supply method in the dorsal hippocampus (DH), while astrocyte-neuron lactate shuttle (ANLS) was involved in the amygdala during memory acquisition
We found that during the basal stage and contextual fear conditioning (CFC) training, 2-NBDG-positive cells in the DH were nearly completely merged with NeuN-positive cells (Figure 1B) and rarely overlapped with GFAP-positive cells (Supplementary Figure S1A), suggesting that 2-NBDG tends to be absorbed by neurons in the DH
Summary
It is well known that a highly active brain accounts for at least 20% of the body’s daily energy consumption. In the central nervous system, the nearly exclusive source of energy is glucose aerobic metabolism Most of this energy is utilized to sustain synaptic transmission, neuronal survival and information processing underlying multiple behaviors such as learning and memory, emotion and sensorimotor activity (Benarroch, 2014). The precise connection of neurons, astrocytes and endothelial cells plays a crucial role in coupling energy supply with neuronal activity (Magistretti and Allaman, 2015). To maintain these high energy demands, neurons can take up Energy Metabolism during Fear Acquisition glucose directly; alternatively, astrocytes can convert glucose into lactate and supply it to neurons (Suzuki et al, 2011; Lundgaard et al, 2015). The exact methods of energy supply during different stages of neuronal function and in different brain areas remain unclear (DiNuzzo et al, 2010; Bélanger et al, 2011; Mangia et al, 2011)
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