title: Characterization of sacral interneurons that mediate activation of locomotor pattern generators by sacrocaudal afferent input.
abstract: Identification of the neural pathways involved in retraining the spinal central pattern generators (CPGs) by afferent input in the absence of descending supraspinal control is feasible in isolated rodent spinal cords where the locomotor CPGs are potently activated by sacrocaudal afferent (SCA) input. Here we study the involvement of sacral neurons projecting rostrally through the ventral funiculi (VF) in activation of the CPGs by sensory stimulation. Fluorescent labeling and immunostaining showed that VF neurons are innervated by primary afferents immunoreactive for vesicular glutamate transporters 1 and 2 and by intraspinal neurons. Calcium imaging revealed that 55% of the VF neurons were activated by SCA stimulation. The activity of VF neurons and the sacral and lumbar CPGs was abolished when non-NMDA receptors in the sacral segments were blocked by the antagonist CNQX. When sacral NMDA receptors were blocked by APV, the sacral CPGs were suppressed, VF neurons with nonrhythmic activity were recruited and a moderate-drive locomotor rhythm developed during SCA stimulation. In contrast, when the sacral CPGs were activated by SCA stimulation, rhythmic and nonrhythmic VF neurons were recruited and the locomotor rhythm was most powerful. The activity of 73 and 27% of the rhythmic VF neurons was in-phase with the ipsilateral and contralateral motor output, respectively. Collectively, our studies indicate that sacral VF neurons serve as a major link between SCA and the hindlimb CPGs and that the ability of SCA to induce stepping can be enhanced by the sacral CPGs. The nature of the ascending drive to lumbar CPGs, the identity of subpopulations of VF neurons, and their potential role in activating the locomotor rhythm are discussed.
authors.affiliation: Department of Medical Neuroscience, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Etlin
authors.forename: Eran
authors.initials: E
authors.lastname: Finkel
authors.forename: Yoav
authors.initials: Y
authors.lastname: Mor
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Donovan
authors.forename: Lili
authors.initials: L
authors.lastname: Anglister
authors.forename: Aharon
authors.initials: A
authors.lastname: Lev-Tov
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D004566:Electrodes; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012445:Sacrococcygeal Region / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium