title: Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.
abstract: Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl(-) concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Roessle Str. 10, 13125 Berlin, Germany.|Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Roessle Str. 10, 13125 Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gödde
authors.affiliation: Department of Basic Neurosciences, School of Medicine, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gschwend
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Roessle Str. 10, 13125 Berlin, Germany.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Puchkov
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Roessle Str. 10, 13125 Berlin, Germany.|Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Roessle Str. 10, 13125 Berlin, Germany.
authors.forename: Carsten K
authors.initials: CK
authors.lastname: Pfeffer
authors.affiliation: Department of Basic Neurosciences, School of Medicine, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Alan
authors.initials: A
authors.lastname: Carleton
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Roessle Str. 10, 13125 Berlin, Germany.|Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Roessle Str. 10, 13125 Berlin, Germany.|NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015870:Gene Expression; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008867:Microtomy; D009812:Odorants / Q000032:analysis; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009833:Olfactory Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055696:Olfactory Perception / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012903:Smell / Q000502:physiology*; D027981:Symporters / Q000172:deficiency / Q000235:genetics*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D014631:Valerates / Q000737:chemistry / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D000096922:K Cl- Cotransporters
chemical_list: D000447:Aldehydes; D027981:Symporters; D014631:Valerates; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C000622367:ethyl valerate; C010463:n-hexanal; C031639:caprylic aldehyde