title: The sound of silence: ionic mechanisms encoding sound termination.
abstract: Offset responses upon termination of a stimulus are crucial for perceptual grouping and gap detection. These gaps are key features of vocal communication, but an ionic mechanism capable of generating fast offsets from auditory stimuli has proven elusive. Offset firing arises in the brainstem superior paraolivary nucleus (SPN), which receives powerful inhibition during sound and converts this into precise action potential (AP) firing upon sound termination. Whole-cell patch recording in vitro showed that offset firing was triggered by IPSPs rather than EPSPs. We show that AP firing can emerge from inhibition through integration of large IPSPs, driven by an extremely negative chloride reversal potential (E(Cl)), combined with a large hyperpolarization-activated nonspecific cationic current (I(H)), with a secondary contribution from a T-type calcium conductance (I(TCa)). On activation by the IPSP, I(H) potently accelerates the membrane time constant, so when the sound ceases, a rapid repolarization triggers multiple offset APs that match onset timing accuracy.
authors: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester LE1 9HN, UK.
authors: Cornelia
authors: C
authors: Kopp-Scheinpflug
authors: Adam J B
authors: AJ
authors: Tozer
authors: Susan W
authors: SW
authors: Robinson
authors: Bruce L
authors: BL
authors: Tempel
authors: Matthias H
authors: MH
authors: Hennig
authors: Ian D
authors: ID
authors: Forsythe
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001306:Auditory Pathways / Q000502:physiology; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency; D004558:Electric Stimulation; D007839:Functional Laterality; D005665:Furosemide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009847:Olivary Nucleus / Q000166:cytology; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000172:deficiency; D011571:Psychoacoustics; D011743:Pyrimidines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D013266:Stilbamidines / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology; D000096922:K Cl- Cotransporters
chemical_list: D002118:Calcium; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D005665:Furosemide; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D020748:Mibefradil; D015221:Potassium Channels; D011743:Pyrimidines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D013266:Stilbamidines; D027981:Symporters; D000096922:K Cl- Cotransporters; C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C082246:ICI D2788