Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons.
The central pattern generator can generate locomotor-like rhythmic activity in the spinal cord in the absence of descending and peripheral inputs, but the motor pattern is regulated by feedback from peripheral sensory inputs that adjust motor outputs to external stimuli. To elucidate the possible role of Hb9-expressing interneurons (Hb9 INs) in the locomotor circuitry, we investigated whether their induced oscillatory activity is modulated by low-threshold afferents in the isolated spinal cords of neonatal Hb9:eGFP transgenic mice. Low-intensity stimulation of segmental afferents generated short-latency, monosynaptic excitatory responses in 62% of Hb9 INs. These were associated with longer-latency (approximately 13 ms) excitatory postsynaptic currents that were evoked in all Hb9 INs, probably by slow conducting afferents that synapse directly onto them. Concomitant morphological analysis confirmed that afferent axons with immunoreactive expression of vesicular glutamate transporter-1 and parvalbumin, presumably from primary afferents, contacted somata and dendrites of all Hb9 INs. Most of the putative synaptic contacts were on distal dendrites that extended to an area with profuse afferent projections. We next examined whether low-threshold afferents in upper (flexor-related) and lower (extensor-related) lumbar segments altered the timing of neurochemically induced locomotor-like rhythms in Hb9 INs and motoneurons. Excitation of flexor-related afferents during the flexor phase delayed the onset of subsequent cycles in both Hb9 INs and segmental motoneurons while maintaining the phase relationship between them. The in-phase correlation between voltage oscillations in Hb9 INs and motor bursts also persisted during the two- to threefold increase in cycle period triggered by extensor-related afferents. Our findings that low-threshold, presumably muscle afferents, synapse directly onto these interneurons and perturb their induced locomotor-like membrane oscillations in a pattern that remains phase-locked with motor bursts support the hypothesis that Hb9 INs are part of the sensorimotor circuitry that regulates the pattern of locomotor rhythms in the isolated cord.
Hinckley
Christopher A
CA
Department of Physiology, University of Wisconsin School of Medicine, 1300 University Avenue, Madison, WI 53706, USA.
Wiesner
Eric P
EP
Mentis
George Z
GZ
Titus
David J
DJ
Ziskind-Conhaim
Lea
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D008124:Locomotion / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D010507:Periodicity; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018398:Homeodomain Proteins; C493465:Slc17a7 protein, mouse; D014157:Transcription Factors; D050598:Vesicular Glutamate Transport Protein 1; C485184:enhanced green fluorescent protein; C084059:Hb9 protein, mouse; D049452:Green Fluorescent Proteins; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate
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