title: Activity-dependent expression of simultaneous glutamatergic and GABAergic neurotransmission from the mossy fibers in vitro.
abstract: GABAergic transmission in the mossy fiber (MF) projection of the hippocampus is not normally detected in the rat. However, seizures induce simultaneous glutamatergic and GABAergic transmission in this projection, which coincides with an overexpression of GAD(67) and vesicular GABA transporter (VGAT) mRNA in the dentate gyrus (DG) and MF. To test whether this plastic change could be induced in an activity-dependent fashion in the absence of seizures, I recorded intracellularly from slices/cells that served as their own control, before and after direct or synaptic kindling of the DG in vitro. As expected, synaptic responses of CA3 pyramidal cells to test pulse DG stimulation were blocked by perfusion of N-methyl-D-aspartate (NMDA) and non-NMDA receptors' antagonists. However, after kindling the perforant path (3 1-s trains of 0.1-ms pulses at 100 Hz, 1 min apart from each other every 15 min for 3 h), which potentiated synaptic responses without inducing epileptiform activity, the perfusion of glutamatergic antagonists blocked the excitatory synaptic potential and isolated a fast bicuculline-sensitive inhibitory synaptic potential. Immunohistochemical experiments confirmed the overexpression of GAD(67) in the kindled slices. If kindling stimulation was provided just for 1 h or if it was completed in the presence of the protein synthesis inhibitor, cycloheximide, the expression of the GABAergic potential was prevented. Alternatively, when control synaptic responses of a given cell were first blocked, the direct kindling stimulation over the same site during perfusion of glutamatergic antagonists resulted in the induction of fast GABAergic potentials after 16.6 +/- 0.9 kindling trials. Furthermore, a high spacial specificity of this phenomenon was evidenced by recording synaptic responses of a given pyramidal cell to two different MF inputs. After blockade of all synaptic responses with the perfusion of glutamatergic antagonists, one of the inputs was kindled, while synaptic responses between the kindling trials were monitored by applying test pulse stimulation to both inputs. After 17 +/- 1 trials, test pulse stimulation provided over the kindled site evoked GABAergic potentials, whereas test pulse stimulation delivered to the alternative nonkindled parallel MF input remained ineffective. The DG-evoked GABAergic responses were inhibited by the activation of GABA(B)R and mGluR, whereby activation of group III mGluR with L-2-amino-4-phosphonobutyric acid (L-AP4) was significantly more effective than the activation of group II mGluR with DCG-IV. These data demonstrate that GABAergic transmission from the MF projection has distinctive features in the adult rat, and that its induction is dependent on protein synthesis responding in an activity-dependent fashion.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico D.F. 07000, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gutiérrez
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D019580:Perforant Pathway / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate