title: Developmental downregulation of excitatory GABAergic transmission in neocortical layer I via presynaptic adenosine A(1) receptors.
abstract: Layer I of the developing cortex contains a dense GABAergic fiber plexus. These fibers provide excitatory inputs to Cajal-Retzius (CR) cells, the early born neurons in layer I. CR cells possess an extensive axonal projection and form synaptic contacts with excitatory, presumably pyramidal, neurons before birth. Interestingly, activity of CR cells declines during the first postnatal week, but mechanism(s) underlying this phenomenon is not yet known. Here we recorded inhibitory postsynaptic currents (IPSCs) in CR cells at postnatal day (P) 1-2 and P5-7. Blockade of adenosine A(1) receptors (A(1)Rs) increased the amplitude of evoked IPSCs (eIPSCs) and decreased paired-pulse ratio at P5-7 but not at P1-2. A(1)R activation decreased the mean eIPSC amplitude at P5-7, but failed to affect eIPSCs at P1-2. Ecto-adenosine triphosphatase (ATPase) inhibition completely abolished the A(1)R-mediated effects suggesting that extracellular ATP is the main source of adenosine. Because A(1)R blockade did not affect the median miniature IPSC amplitude, our results demonstrate that adenosine reduces gamma-aminiobutyric acid (GABA) release probability via presynaptic A(1)Rs at P5-7. As neuronal activity in layer I can depolarize pyramidal neurons influencing thereby glutamatergic synaptogenesis in the lower cortical layers, postnatal weakening of GABAergic transmission by adenosinergic system might reflect a developmental downregulation of this excitatory drive when glutamatergic synapses are formed.
authors.affiliation: Institute of Neurophysiology, Johannes-Mueller-Center of Physiology, Charité-University-Medicine Berlin, Tucholskystr. 2, 10117 Berlin, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Kirmse
authors.forename: Anton
authors.initials: A
authors.lastname: Dvorzhak
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Grantyn
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015536:Down-Regulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D043682:Receptor, Adenosine A1; D005680:gamma-Aminobutyric Acid