On-Site Energy Supply at Synapses through Monocarboxylate Transporters Maintains Excitatory Synaptic Transmission

• DOI: 10.1523/jneurosci.4687-12.2014
• Publication Date: 2014-02-12T17:28:13Z
• Authors: Masashi Nagase; Yukari Takahashi; Ayako M. Watabe; Yoshihiro Kubo; Fusao Kato
• Keywords: Male; Monocarboxylic Acid Transporters; 0301 basic medicine; Patch-Clamp Techniques; Xenopus; Excitatory Postsynaptic Potentials; Synaptic Transmission; Rats; 03 medical and health sciences; Organ Culture Techniques; Synapses; Solitary Nucleus; Animals; Female; Rats, Wistar; Energy Metabolism

ATP production through oxidative phosphorylation in the mitochondria is most efficient way to provide energy various energy-consuming activities of neurons. These processes require a large amount molecules be maintained. Of these, synaptic transmission consuming. Here we report that lactate transported monocarboxylate transporters (MCTs) at excitatory synapses constitutively supports transmission, even under conditions which sufficient supply glucose and intracellular are present. We analyzed effects MCT inhibition on neuronal using whole-cell recordings brain slices rats nucleus solitary tract. inhibitors (α-cyano-4-hydroxycinnamic acid (4-CIN), phloretin, d-lactate) significantly decreased amplitude EPSCs without reducing release probability. Although 4-CIN reduced currents mediated by heterologously expressed AMPA-Rs oocytes (a novel finding this study), IC50 inhibitory effect EPSC was ∼3.8 times smaller than AMPA-R oocytes. Removal potentiated with manner counteracted addition. In addition, extracellular rescued aglycemic suppression EPSC, prevented 4-CIN. Inhibition MCTs also NMDA-R-mediated and, lesser extent, IPSC. The reduction γ-d-glutamylglycine enhanced 4-CIN, suggesting quantal content. conclude "on-site" astrocyte-neuron transport presynaptic postsynaptic elements necessary for integrity transmission.