Identification of Minimal Neuronal Networks Involved in Flexor-Extensor Alternation in the Mammalian Spinal Cord

• Published in: Neuron (Cambridge, Mass.) Vol. 71; no. 6; pp. 1071 - 1084
• Main Authors: Talpalar, Adolfo E., Endo, Toshiaki, Löw, Peter, Borgius, Lotta, Hägglund, Martin, Dougherty, Kimberly J., Ryge, Jesper, Hnasko, Thomas S., Kiehn, Ole
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.09.2011; Elsevier Limited
• Subjects: Action Potentials - physiology; Animals; GABA Antagonists - pharmacology; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; Glycine - metabolism; Glycine Agents - pharmacology; Interneurons - physiology; Mammals; Medicin och hälsovetenskap; Mice; Mice, Knockout; Motor Activity - physiology; Motor Neurons - drug effects; Motor Neurons - physiology; Muscle Contraction - physiology; Muscle, Skeletal - innervation; Muscle, Skeletal - physiology; Nerve Net - anatomy & histology; Nerve Net - physiology; Neural networks; Neurons; Periodicity; Picrotoxin - pharmacology; Receptors, GABA-A - metabolism; Receptors, Glycine - metabolism; Rhythm; Rodents; Spinal cord; Spinal Cord - cytology; Spinal Cord - physiology; Strychnine - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vesicular Glutamate Transport Protein 2 - genetics; Vesicular Glutamate Transport Protein 2 - metabolism
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2011.07.011

Neural networks in the spinal cord control two basic features of locomotor movements: rhythm generation and pattern generation. Rhythm generation is generally considered to be dependent on glutamatergic excitatory neurons. Pattern generation involves neural circuits controlling left-right alternation, which has been described in great detail, and flexor-extensor alternation, which remains poorly understood. Here, we use a mouse model in which glutamatergic neurotransmission has been ablated in the locomotor region of the spinal cord. The isolated in vitro spinal cord from these mice produces locomotor-like activity—when stimulated with neuroactive substances—with prominent flexor-extensor alternation. Under these conditions, unlike in control mice, networks of inhibitory interneurons generate the rhythmic activity. In the absence of glutamatergic synaptic transmission, the flexor-extensor alternation appears to be generated by Ia inhibitory interneurons, which mediate reciprocal inhibition from muscle proprioceptors to antagonist motor neurons. Our study defines a minimal inhibitory network that is needed to produce flexor-extensor alternation during locomotion. ► Inhibitory networks assemble a minimal rhythm- and pattern-generating locomotor module ► Reciprocal inhibition among IaINs produces the basic flexor-extensor alternation