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Developmental biology - Brain Function|
Mapping nerve connections from brain-to-spinal cord
However, the scientists believe it will take more years of investigative work to make certain the current findings are therapeutically relevant. So, they are conducting more studies to build on this newly identified basic neural architecture.
The Schematics of Corticospinal Connections
Little has been known about how the corticospinal network of nerves between the brain and spinal cord are organized or function together. Simple tasks like reaching or grabbing require precise coordination between sensory and motor responses transmitted through neuronal connections. To map this connectivity, scientists studied these circuits in laboratory mice — taking advantage of the similarity between corticospinal connections in primates, cats, and rodents.
Working from previous studies by his team and others, Yoshida and colleagues traced corticospinal connections from the cerebral cortex near the top of the head, down through the spinal cord. They also traced through mouse genetics, how corticospinal circuits connections are organized and function, with a viral tracer (a de-armed rabies virus) that allowed them to capture images of these links.
In his paper, Yoshida explains how his team was able to map corticospinal neurons controlling sensory nerve impulses, while also identifying neurons that affect finely tuned muscular response. In such areas, scientists saw how nerve fibers connect with certain premotor interneurons to transmit impulses to neurons triggering fine muscular responses. This includes nerve fibers that express a transcription factor called Chx10 — a regulator gene which initiates the turning "on" or "off" of finely tuned muscular response. Chx10 is linked to nervous system function in areas such as the eyes. When researchers silenced (turned off) Chx10 in the cervical spinal cord, an animals' ability to reach for food became impaired.
The Importance of How We Sense
The map also highlights connections between the cortex and corticospinal neurons — which control an animals' ability to sense and convert external stimuli into electrical impulses. This in contrast to corticospinal neurons in the motor cortex that directly trigger specific skilled movements. Corticospinal neurons in the sensory cortex do not connect directly to premotor neurons. Instead, they connect directly to other spinal interneurons that turn on a gene called Vglut3. When scientists inhibited neurons in the cervical spinal cord expressing Vglut3, it caused difficulty in an animals' ability to grab and release food pellets — a goal-oriented task.
• Mouse CS axons from motor and sensory cortices project to distinct spinal regions
• We map connectivity between CS neurons and various spinal interneurons
• CS neurons in motor cortex control reaching via spinal Chx10+ interneurons
• CS neurons in sensory cortex control food release via spinal Vglut3+ interneurons
Little is known about the organizational and functional connectivity of the corticospinal (CS) circuits that are essential for voluntary movement. Here, we map the connectivity between CS neurons in the forelimb motor and sensory cortices and various spinal interneurons, demonstrating that distinct CS-interneuron circuits control specific aspects of skilled movements. CS fibers originating in the mouse motor cortex directly synapse onto premotor interneurons, including those expressing Chx10. Lesions of the motor cortex or silencing of spinal Chx10+ interneurons produces deficits in skilled reaching. In contrast, CS neurons in the sensory cortex do not synapse directly onto premotor interneurons, and they preferentially connect to Vglut3+ spinal interneurons. Lesions to the sensory cortex or inhibition of Vglut3+ interneurons cause deficits in food pellet release movements in goal-oriented tasks. These findings reveal that CS neurons in the motor and sensory cortices differentially control skilled movements through distinct CS-spinal interneuron circuits.
Authors: Masaki Ueno, Yuka Nakamura, Jie Li, Zirong Gu, Jesse Niehaus, Mari Maezawa, Steven A. Crone, Martyn Goulding, Mark L. Baccei, Yutaka Yoshida. The authors declare no competing interests.
Thank you to L. Enquist and the Center for Neuroanatomy with Neurotropic Viruses (CNNV; NIH grant P40RR018604) at Princeton University for providing PRVs; E. Callaway for rabies viruses; A. Joyner, C. Wright, A. Pierani, Y. Nakagawa, L. Sussel, R. Johnson, A. Kania, J. Robbins, and G. Feng for providing mice; J. Martin, N. Serradj, and J. Kalambogias (CUNY School of Medicine) for instruction on ICMS; K. Katayama, F. Imai, P. Thanh, A. Epstein, and M. Sandy (CCHMC) for their technical assistance; M. Masujima (NRIFS) for helping with heatmap analyses; M. Kamoshita, J. Ito (Azabu Univ), X. Sun (CCHMC), and T. Daikoku (Kanazawa University) for help in sperm cryopreservation; T. Yamashita (Osaka University), K. Shibuki, and O. Onodera (Niigata University) for supporting materials; and J. Martin for critical reading of the manuscript. This work was supported by NINDS-NS093002 (Y.Y.); PRESTO (JST; JPMJPR13M8); JSPS KAKENHI 17H04985, 17H05556, and 17K19443; JSPS Postdoctoral Fellowships for Research Abroad; the KANAE Foundation for the Promotion of Medical Science; the Kato Memorial Bioscience Foundation; Grant-in-Aid from the Tokyo Biochemical Research Foundation; the Narishige Neuroscience Research Foundation; and a Japan Heart Foundation Research Grant (M.U.).
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This microscopic image shows corticospinal neurons and synaptic connections to the spinal cord in a mouse. Spinal interneurons (blue) show synaptic connections (in green) with corticospinal axons (red). Researchers report in Cell Reports the mapping of critical nerve connections to the spine that drive voluntary movement in forelimbs. The gridlines allow scientists to plot neuron locations along the spinal cord. Information useful to specific repair strategies for stroke and spinal cord injury.