title: Plasticity of the GABAergic phenotype of the "glutamatergic" granule cells of the rat dentate gyrus.
abstract: The "glutamatergic" granule cells of the dentate gyrus transiently express a GABAergic phenotype when a state of hyperexcitability is induced in the adult rat. Consequently, granule cell (GC) activation provokes monosynaptic GABAergic responses in their targets of area CA3. Because GABA exerts a trophic action on neonatal CA3 and mossy fibers (MF) constitute its main input, we hypothesized that the GABAergic phenotype of the MF could also be transiently expressed early in life. We addressed this possibility with a multidisciplinary approach. Electrophysiological recordings in developing rats revealed that, until day 22-23 of age, glutamate receptor antagonists block the excitatory response evoked in pyramidal cells by GCs, isolating a fast metabotropic glutamate receptor-sensitive GABAergic response. In a clear-cut manner from day 23-24 of age, GC activation in the presence of glutamatergic antagonists was unable to evoke synaptic responses in CA3. Immunohistological experiments showed the presence of GABA and GAD67 (glutamate decarboxylase 67 kDa isoform) in the developing GCs and their MF, and, using reverse transcription-PCR, we confirmed the expression of vesicular GABA transporter mRNA in the developing dentate gyrus and its downregulation in the adult. The GABAergic markers were upregulated and MF inhibitory transmission reappeared when hyperexcitability was induced in adult rats. Our data evidence for the first time a developmental and activity-dependent regulation of the complex phenotype of the GC. At early ages, the GABAergic input from the MF may add to the interneuronal input to CA3 to foster development, and, in the adult, it can possibly protect the system from enhanced excitability.
authors.affiliation: Departamento de Fisiología, Biofìsica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México 07000. grafael@fisio.cinvestav.mx
authors.forename: Rafael
authors.initials: R
authors.lastname: Gutiérrez
authors.forename: Héctor
authors.initials: H
authors.lastname: Romo-Parra
authors.forename: Jasmín
authors.initials: J
authors.lastname: Maqueda
authors.forename: Carmen
authors.initials: C
authors.lastname: Vivar
authors.forename: Mónica
authors.initials: M
authors.lastname: Ramìrez
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Morales
authors.forename: Mónica
authors.initials: M
authors.lastname: Lamas
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D027361:Organic Anion Transporters; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid