Reciprocal Connections Between Cortex and Thalamus Contribute to Retinal Axon Targeting to Dorsal Lateral Geniculate Nucleus.
The dorsal Lateral Geniculate Nucleus (dLGN) is the primary image-forming target of the retina and shares a reciprocal connection with primary visual cortex (V1). Previous studies showed that corticothalamic input is essential for the development of thalamocortical projections, but less is known about the potential role of this reciprocal connection in the development of retinal projections. Here, we show a deficit of retinal innervation in the dLGN around E18.5 in Tra2β conditional knockout (cKO) "cortexless" mice, an age when apoptosis occurs along the thalamocortical tract and in some dLGN neurons. In vivo electrophysiology experiments in the dLGN further confirmed the loss of functional retinal input. Experiments with N-methyl-d-aspartic acid-induced V1 lesion as well as Fezf2 cKO mice confirmed that the disruption of connections between the dLGN and V1 lead to abnormal retinal projections to the dLGN. Interestingly, retinal projections to the ventral Lateral Geniculate Nucleus (vLGN) and Superior Colliculus (SC) were normal in all 3 mice models. Finally, we show that the cortexless mice had worse performance than control mice in a go-no go task with visual cues. Our results provide evidence that the wiring of visual circuit from the retina to the dLGN and V1 thereafter is coordinated at a surprisingly early stage of circuit development.
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200 032, China.
Yupu
Y
Diao
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200 032, China.
Liyuan
L
Cui
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200 032, China.
Yuqing
Y
Chen
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06 510, USA.
Timothy J
TJ
Burbridge
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06 510, USA.
Wenqi
W
Han
Institute of Human Genetics, Institute for Genetics, Center for Molecular Medicine Cologne, University of Cologne, Cologne 55322, Germany.
Brunhilde
B
Wirth
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06 510, USA.
Nenad
N
Sestan
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06 510, USA.
Michael C
MC
Crair
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200 032, China.
Jiayi
J
Zhang
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000633:toxicity; D002772:Cholera Toxin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005247:Feeding Behavior / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005829:Geniculate Bodies / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D012160:Retina / Q000166:cytology*; D000068103:Serine-Arginine Splicing Factors / Q000172:deficiency / Q000235:genetics; D013477:Superior Colliculi / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014793:Visual Cortex / Q000293:injuries / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology*; D000099260:Empty Spiracles Homeobox Proteins
D002118:Calcium; D002772:Cholera Toxin; D004268:DNA-Binding Proteins; D018690:Excitatory Amino Acid Agonists; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000068103:Serine-Arginine Splicing Factors; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C100345:Tra2b protein, mouse; C412364:Zfp312 protein, mouse