title: Cell-specific activity-dependent fractionation of layer 2/3→5B excitatory signaling in mouse auditory cortex.
abstract: Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input-output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input-output functions.
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261.
authors.forename: Ankur
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261.
authors.forename: Jason W
authors.identifier: http://orcid.org/0000-0002-4309-5252
authors.initials: JW
authors.lastname: Middleton
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Anderson
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors.forename: Katharine
authors.initials: K
authors.lastname: Borges
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors.forename: Benjamin A
authors.identifier: http://orcid.org/0000-0002-9885-6936
authors.initials: BA
authors.lastname: Suter
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and Whitman Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543.
authors.forename: Gordon M G
authors.initials: GM
authors.lastname: Shepherd
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, Whitman Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543 thanos@pitt.edu.
authors.forename: Thanos
authors.initials: T
authors.lastname: Tzounopoulos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000166:cytology*; D001306:Auditory Pathways / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005420:Flavoproteins / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005420:Flavoproteins; D018756:GABA Antagonists; D011724:Pyridazines; D011810:Quinoxalines; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C049853:gabazine; D014633:Valine
keywords: auditory cortex; cortical mechanisms; intrinsic mechanisms; short-term plasticity; synaptic mechanisms