title: Absence of plateau potentials in dLGN cells leads to a breakdown in retinogeniculate refinement.
abstract: The link between neural activity and the refinement of projections from retina to the dorsal lateral geniculate nucleus (dLGN) of thalamus is based largely on studies that disrupt presynaptic retinogeniculate activity. Postsynaptic mechanisms responsible for implementing the activity-dependent remodeling in dLGN remain unknown. We tested whether L-type Ca(2+) channel activity in the form of synaptically evoked plateau potentials in dLGN cells is needed for remodeling by using a mutant mouse that lacks the ancillary β3 subunit and, as a consequence, has highly reduced L-type channel expression and attenuated L-type Ca(2+) currents. In the dLGNs of β3-null mice, glutamatergic postsynaptic activity evoked by optic tract stimulation was normal, but plateau potentials were rarely observed. The few plateaus that were evoked required high rates of retinal stimulation, but were still greatly attenuated compared with those recorded in age-matched wild-type mice. While β3-null mice exhibit normal stage II and III retinal waves, their retinogeniculate projections fail to segregate properly and dLGN cells show a high degree of retinal convergence even at late postnatal ages. These structural and functional defects were also accompanied by a reduction in CREB phosphorylation, a signaling event that has been shown to be essential for retinogeniculate axon segregation. Thus, postsynaptic L-type Ca(2+) activity plays an important role in mediating the refinement of the retinogeniculate pathway.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Dilger
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Krahe
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Morhardt
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Health Sciences Center, Louisville, Kentucky 40292.
authors.forename: Tania A
authors.identifier: http://orcid.org/0000-0001-6392-1948
authors.initials: TA
authors.lastname: Seabrook
authors.affiliation: Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea, and.
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Health Sciences Center, Louisville, Kentucky 40292 william.guido@louisville.edu.
authors.forename: William
authors.initials: W
authors.lastname: Guido
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D005829:Geniculate Bodies / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000502:physiology*; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D021122:Protein Subunits
keywords: activity-dependent refinement; l-type Ca2+ channel; lateral geniculate nucleus; retina; retinogeniculate; β3-null mice