title: A structural and genotypic scaffold underlying temporal integration.
abstract: The accumulation and storage of information over time, temporal integration, is key to numerous behaviors. Many oculomotor tasks depend on integration of eye-velocity signals to eye-position commands, a transformation achieved by a hindbrain cell group termed the velocity-to-position neural integrator (VPNI). Although the VPNI's coding properties have been well characterized, its mechanism of function remains poorly understood because few links exist between neuronal activity, structure, and genotypic identity. To fill this gap, we used calcium imaging and single-cell electroporation during oculomotor behaviors to map VPNI neural activity in zebrafish onto a hindbrain scaffold consisting of alternating excitatory and inhibitory parasagittal stripes. Three distinct classes of VPNI cells were identified. One glutamatergic class was medially located along a stripe associated with the alx transcription factor; these cells had ipsilateral projections terminating near abducens motoneurons and collateralized extensively within the ipsilateral VPNI in a manner consistent with integration through recurrent excitation. A second glutamatergic class was more laterally located along a stripe associated with transcription factor dbx1b; these glutamatergic cells had contralateral projections collateralizing near abducens motoneurons, consistent with a role in disconjugate eye movements. A third class, immunohistochemically suggested to be GABAergic, was located primarily in the dbx1b stripe and also had contralateral projections terminating near abducens motoneurons; these cells collateralized extensively in the dendritic field of contralateral VPNI neurons, consistent with a role in coordinating activity between functionally opposing populations. This mapping between VPNI activity, structure, and genotype may provide a blueprint for understanding the mechanisms governing temporal integration.
authors.affiliation: Institute for Computational Biomedicine and the Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10021, and.
authors.forename: Melanie M
authors.identifier: http://orcid.org/0000-0002-8498-0733
authors.initials: MM
authors.lastname: Lee
authors.affiliation: Developmental Biology, Institute Biology 1, Faculty of Biology and Center for Biological Signaling Studies, University of Freiburg, D-79104, Freiburg, Germany.
authors.forename: Aristides B
authors.identifier: http://orcid.org/0000-0001-8262-7381
authors.initials: AB
authors.lastname: Arrenberg
authors.affiliation: Institute for Computational Biomedicine and the Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10021, and ema2004@med.cornell.edu.
authors.forename: Emre R F
authors.identifier: http://orcid.org/0000-0002-4561-4175
authors.initials: ER
authors.lastname: Aksay
mesh_terms: D000818:Animals; D005133:Eye Movements; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D059330:GABAergic Neurons / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490001:dbx1b protein, zebrafish; C108000:vsx2 protein, zebrafish
keywords: eye movements; microcircuit; neural integrator; patterning; persistent activity; temporal integration