Imagine a dance performance where every dancer moves in perfect harmony, creating a captivating spectacle. Similar to this synchrony, vertebrates rely on spinal networks called central pattern generators (CPGs) to produce the coordinated movement of locomotion. A recent computational study delved into the intricate mechanisms behind locomotion and force generation by investigating the modulation of ionic channels in these spinal networks. By tinkering with specific channels, such as voltage-gated sodium channels (VGSC), persistent sodium channels (NaP), and L-type calcium channels (LTCC), researchers found that they could enhance the rhythmic generation of locomotion and boost muscle force production. On the other hand, inhibiting these channels disrupted the delicate dance, resulting in a blocked output of muscle force. The study also observed that altering channel properties in both excitatory interneuron pools and motor neurons had profound effects on the overall locomotor pattern, firing frequency, and duration of step cycles. These findings contribute to our understanding of how spinal networks orchestrate movements and could potentially offer insights into therapeutic approaches for disorders affecting locomotion. To dive deeper into the world of CPGs and their role in locomotion, explore the full research article!

Locomotion is a fundamental movement in vertebrates produced by spinal networks known as central pattern generators (CPG). During fictive locomotion cat lumbar motoneurons (MNs) exhibit changes in membrane properties, including hyperpolarization of voltage threshold, reduction of afterhyperpolarization and input resistance, and amplification of nonlinear membrane properties. Both modeling and electrophysiological studies suggest that these changes can be produced by upregulating voltage-gated sodium channel (VGSC), persistent sodium (NaP), or L-type calcium channel (LTCC) or downregulating delayed-rectifier potassium (K(DR)) or calcium-dependent potassium channel (KCa) in spinal MNs. Further studies implicate that these channel modulations increase motor output and facilitate MN recruitment. However, it remains unknown how the channel modulation of CPG networks or MN pools affects the rhythmic generation of locomotion and force production of skeletal muscle during locomotion. In order to investigate this issue, we built a two-level CPG model composed of excitatory interneuron pools (Exc-INs), coupled reciprocally with inhibitory interneuron pools (Inh-INs), and projected to the flexor-extensor MN pools innervating skeletal muscles. Each pool consisted of 100 neurons with membrane properties based on cat spinal neurons. VGSC, K(DR), NaP, KCa, LTCC, and H-current channels were included in the model. Simulation results showed that (1) upregulating VGSC, NaP, or LTCC or downregulating KCa in MNs increased discharge rate and recruitment of MNs, thus facilitating locomotor pattern formation, increased amplitude of electroneurogram (ENG) bursting, and enhanced force generation of skeletal muscles. (2) The same channel modulation in Exc-INs increased the firing frequency of the Exc-INs, facilitated rhythmic generation, and increased flexor-extensor durations of step cycles. (3) Contrarily, downregulation of NaP or LTCC in MNs or Exc-INs or both CPG (Exc-INs and Inh-INs) and MNs disrupted locomotor pattern and reduced or even blocked the ENG bursting of MNs and force generation of skeletal muscles. (4) Pharmacological experiments showed that bath application of 25 μM nimodipine or 2 μM riluzole completely blocked fictive locomotion in isolated rat spinal cord, consistent with simulation results. We concluded that upregulation of VGSC, NaP, or LTCC or downregulation of KCa facilitated rhythmic generation and force production during walking, with NaP and LTCC playing an essential role.

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