title: Cortical Feedback Regulates Feedforward Retinogeniculate Refinement.
abstract: According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection.
authors.affiliation: BBS Program, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Thompson
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Picard
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Min
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: chinfei.chen@childrens.harvard.edu.
authors.forename: Chinfei
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003423:Critical Period, Psychological; D025461:Feedback, Physiological / Q000502:physiology*; D005829:Geniculate Bodies / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*; D014795:Visual Pathways / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
chemical_list: D009118:Muscimol; D003024:Clozapine; C079149:clozapine N-oxide