ABSTRACT
Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORß orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORß IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORß in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORß inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. VIDEO ABSTRACT.
Subject(s)
Interneurons/physiology , Locomotion/physiology , Nuclear Receptor Subfamily 1, Group F, Member 2/metabolism , Spinal Cord/cytology , Walking/physiology , Afferent Pathways , Animals , Animals, Newborn , Electric Stimulation , Feedback, Sensory , GABA Agents/pharmacology , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , Glycine Plasma Membrane Transport Proteins/genetics , Glycine Plasma Membrane Transport Proteins/metabolism , Hip Joint/innervation , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Muscle, Skeletal/physiology , Neural Inhibition/genetics , Neural Inhibition/physiology , Nuclear Receptor Subfamily 1, Group F, Member 2/genetics , PAX2 Transcription Factor/genetics , PAX2 Transcription Factor/metabolism , Reflex/genetics , Reflex/physiology , Sensory Thresholds/physiologyABSTRACT
Sensory circuits in the dorsal spinal cord integrate and transmit multiple cutaneous sensory modalities including the sense of light touch. Here, we identify a population of excitatory interneurons (INs) in the dorsal horn that are important for transmitting innocuous light touch sensation. These neurons express the ROR alpha (RORα) nuclear orphan receptor and are selectively innervated by cutaneous low threshold mechanoreceptors (LTMs). Targeted removal of RORα INs in the dorsal spinal cord leads to a marked reduction in behavioral responsiveness to light touch without affecting responses to noxious and itch stimuli. RORα IN-deficient mice also display a selective deficit in corrective foot movements. This phenotype, together with our demonstration that the RORα INs are innervated by corticospinal and vestibulospinal projection neurons, argues that the RORα INs direct corrective reflex movements by integrating touch information with descending motor commands from the cortex and cerebellum.
Subject(s)
Mechanotransduction, Cellular , Neural Pathways , Spinal Cord Dorsal Horn/metabolism , Touch , Animals , Interneurons/metabolism , Mice , Motor Activity , Motor Neurons/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism , Spinal Cord Dorsal Horn/cytology , SynapsesABSTRACT
Interneurons in the dorsal spinal cord process and relay innocuous and nociceptive somatosensory information from cutaneous receptors that sense touch, temperature and pain. These neurons display a well-defined organization with respect to their afferent innervation. Nociceptive afferents innervate lamina I and II, while cutaneous mechanosensory afferents primarily innervate sensory interneurons that are located in lamina III-IV. In this study, we outline a combinatorial transcription factor code that defines nine different inhibitory and excitatory interneuron populations in laminae III-IV of the postnatal cord. This transcription factor code reveals a high degree of molecular diversity in the neurons that make up laminae III-IV, and it lays the foundation for systematically analyzing and manipulating these different neuronal populations to assess their function. In addition, we find that many of the transcription factors that are expressed in the dorsal spinal cord at early postnatal times continue to be expressed in the adult, raising questions about their function in mature neurons and opening the door to their genetic manipulation in adult animals.
