Abstract
Growing evidence supports the notion that brain-derived neurotrophic factor (BDNF) and lactate are potent modulators of mammalian brain function. The modulatory actions of those biomolecules influence a wide range of neuronal responses, from the shaping of neuronal excitability to the induction and expression of structural and synaptic plasticity. The biological actions of BDNF and lactate are mediated by their cognate receptors and specific transporters located in the neuronal membrane. Canonical functions of BDNF occur via the tropomyosin-related kinase B receptor (TrkB), whereas lactate acts via monocarboxylate transporters or the hydroxycarboxylic acid receptor 1 (HCAR1). Both receptors are highly expressed in the central nervous system, and some of their physiological actions are particularly well characterized in the hippocampus, a brain structure involved in the neurophysiology of learning and memory. The multifarious neuronal circuitry between the axons of the dentate gyrus granule cells, mossy fibers (MF), and pyramidal neurons of area CA3 is of great interest given its role in specific mnemonic processes and involvement in a growing number of brain disorders. Whereas the modulation exerted by BDNF via TrkB has been extensively studied, the influence of lactate via HCAR1 on the properties of the MF–CA3 circuit is an emerging field. In this review, we discuss the role of both systems in the modulation of brain physiology, with emphasis on the hippocampal CA3 network. We complement this review with original data that suggest cross-modulation is exerted by these two independent neuromodulatory systems.
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References
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Acknowledgements
The authors wish to thank Center for Research and Advanced Studies (Cinvestav) and the National Council of Humanities, Science and Technology (CONAHCyT) for the funding. Thanks are extended to Dr. Deisy Segura-Villalobos and Dr. Gabriel Herrera-López for their insightful comments and M.Sc. Roberto Olvera for his help in conducting some preliminary experiments.
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This work was supported by the National Council of Humanities, Science and Technology (CONAHCyT) Grant CB-2016-281617 to EJG. Additional funding was provided with doctoral fellowship 727269 (EG) by CONAHCyT.
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EG and EJG as senior authors contributed equally to the conceptualization and design of the review structure and manuscript writing. EG performed the literature search and prepared the figures. EJG supervised the project and provided critical revisions to the manuscript. Both authors reviewed and approved the final version of the manuscript for publication.
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Griego, E., Galván, E.J. BDNF and Lactate as Modulators of Hippocampal CA3 Network Physiology. Cell Mol Neurobiol 43, 4007–4022 (2023). https://doi.org/10.1007/s10571-023-01425-6
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DOI: https://doi.org/10.1007/s10571-023-01425-6