title: Forward suppression in the auditory cortex is caused by the Ca(v)3.1 calcium channel-mediated switch from bursting to tonic firing at thalamocortical projections.
abstract: Brief sounds produce a period of suppressed responsiveness in the auditory cortex (ACx). This forward suppression can last for hundreds of milliseconds and might contribute to mechanisms of temporal separation of sounds and stimulus-specific adaptation. However, the mechanisms of forward suppression remain unknown. We used in vivo recordings of sound-evoked responses in the mouse ACx and whole-cell recordings, two-photon calcium imaging in presynaptic terminals, and two-photon glutamate uncaging in dendritic spines performed in brain slices to show that synaptic depression at thalamocortical (TC) projections contributes to forward suppression in the ACx. Paired-pulse synaptic depression at TC projections lasts for hundreds of milliseconds and is attributable to a switch between firing modes in thalamic neurons. Thalamic neurons respond to a brief depolarizing pulse with a burst of action potentials; however, within hundreds of milliseconds, the same pulse repeated again produces only a single action potential. This switch between firing modes depends on Ca(v)3.1 T-type calcium channels enriched in thalamic relay neurons. Pharmacologic inhibition or knockdown of Ca(v)3.1 T-type calcium channels in the auditory thalamus substantially reduces synaptic depression at TC projections and forward suppression in the ACx. These data suggest that Ca(v)3.1-dependent synaptic depression at TC projections contributes to mechanisms of forward suppression in the ACx.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Ildar T
authors.initials: IT
authors.lastname: Bayazitov
authors.forename: Joby J
authors.initials: JJ
authors.lastname: Westmoreland
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology; D013788:Thalamus / Q000502:physiology*
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D018698:Glutamic Acid