title: Investigation of synapse formation and function in a glutamatergic-GABAergic two-neuron microcircuit.
abstract: Neural circuits are composed of mainly glutamatergic and GABAergic neurons, which communicate through synaptic connections. Many factors instruct the formation and function of these synapses; however, it is difficult to dissect the contribution of intrinsic cell programs from that of extrinsic environmental effects in an intact network. Here, we perform paired recordings from two-neuron microculture preparations of mouse hippocampal glutamatergic and GABAergic neurons to investigate how synaptic input and output of these two principal cells develop. In our reduced preparation, we found that glutamatergic neurons showed no change in synaptic output or input regardless of partner neuron cell type or neuronal activity level. In contrast, we found that glutamatergic input caused the GABAergic neuron to modify its output by way of an increase in synapse formation and a decrease in synaptic release efficiency. These findings are consistent with aspects of GABAergic synapse maturation observed in many brain regions. In addition, changes in GABAergic output are cell wide and not target-cell specific. We also found that glutamatergic neuronal activity determined the AMPA receptor properties of synapses on the partner GABAergic neuron. All modifications of GABAergic input and output required activity of the glutamatergic neuron. Because our system has reduced extrinsic factors, the changes we saw in the GABAergic neuron due to glutamatergic input may reflect initiation of maturation programs that underlie the formation and function of in vivo neural circuits.
authors.affiliation: Neuroscience Research Center, Graduate Program in Medical Neuroscience, and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany, and Departments of Neuroscience and Molecular and Human Genetics and Jan and Dan Duncan Neurological Research Institute, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chang
authors.forename: Thorsten
authors.initials: T
authors.lastname: Trimbuch
authors.forename: Hsiao-Tuan
authors.initials: HT
authors.lastname: Chao
authors.forename: Julia-Christine
authors.initials: JC
authors.lastname: Jordan
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Herman
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000254:growth & development; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000254:growth & development*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D018698:Glutamic Acid
keywords: GABAergic neuron; activity dependent; cell autonomous; cell culture; release probability; synapse formation