title: EphA signaling impacts development of topographic connectivity in auditory corticofugal systems.
abstract: Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of EphA receptor signaling in the development of corticothalamic (CT) and corticocollicular connections. Early in postnatal development, CT axons were restricted to a deep dorsal zone (DDZ) within the MGB that expressed low levels of the ephrin-A ligand. By hearing onset, CT axons had innervated surrounding regions of MGB in control-electroporated mice but remained fixed within the DDZ in mice overexpressing EphA7. In vivo neurophysiological recordings demonstrated a corresponding reduction in spontaneous firing rate, but no changes in sound-evoked responsiveness within MGB regions deprived of CT innervation. Structural and functional CT disruption occurred without gross alterations in thalamocortical connectivity. These data demonstrate a potential role for EphA/ephrin-A signaling in the initial guidance of corticofugal axons and suggest that "genetic rewiring" may represent a useful functional tool to alter cortical feedback without silencing Actx.
authors.affiliation: Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA. masaaki.torii@yale.edu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Torii
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hackett
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Polley
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D000596:Amino Acids; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001306:Auditory Pathways / Q000502:physiology*; D001369:Axons / Q000502:physiology; D001931:Brain Mapping; D004569:Electroencephalography; D018274:Electroporation; D004622:Embryo, Mammalian; D005072:Evoked Potentials, Auditory / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005829:Geniculate Bodies / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D036141:Receptor, EphA7 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000596:Amino Acids; D012333:RNA, Messenger; D050598:Vesicular Glutamate Transport Protein 1; C098463:dolaisoleucine; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D036141:Receptor, EphA7