Adult spinal Dmrt3 neurons receive direct somatosensory inputs from ipsi- and contralateral primary afferents and from brainstem motor nuclei.
Abstract: In the spinal cord, sensory-motor circuits controlling motor activity are situated in the dorso-ventral interface. The neurons identified by the expression of the transcription factor Doublesex and mab-3 related transcription factor 3 (Dmrt3) have previously been associated with the coordination of locomotion in horses (Equus caballus, Linnaeus, 1758), mice (Mus musculus, Linnaeus, 1758), and zebrafish (Danio rerio, F. Hamilton, 1822). Based on earlier studies, we hypothesized that, in mice, these neurons may be positioned to receive sensory and central inputs to relay processed commands to motor neurons. Thus, we investigated the presynaptic inputs to spinal Dmrt3 neurons using monosynaptic retrograde replication-deficient rabies tracing. The analysis showed that lumbar Dmrt3 neurons receive inputs from intrasegmental neurons, and intersegmental neurons from the cervical, thoracic, and sacral segments. Some of these neurons belong to the excitatory V2a interneurons and to plausible Renshaw cells, defined by the expression of Chx10 and calbindin, respectively. We also found that proprioceptive primary sensory neurons of type Ia2, Ia3, and Ib, defined by the expression of calbindin, calretinin, and Brn3c, respectively, provide presynaptic inputs to spinal Dmrt3 neurons. In addition, we demonstrated that Dmrt3 neurons receive inputs from brain areas involved in motor regulation, including the red nucleus, primary sensory-motor cortex, and pontine nuclei. In conclusion, adult spinal Dmrt3 neurons receive inputs from motor-related brain areas as well as proprioceptive primary sensory neurons and have been shown to connect directly to motor neurons. Dmrt3 neurons are thus positioned to provide sensory-motor control and their connectivity is suggestive of the classical reflex pathways present in the spinal cord.
© 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.
Publication Date: 2022-10-10 PubMed ID: 36214727PubMed Central: PMC9828095DOI: 10.1002/cne.25405Google Scholar: Lookup
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Summary
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This research studied how neurons defined by the transcription of the molecule Dmrt3 in the spinal cord receive sensory and central inputs in order to relay instructions to other motor neurons. The results revealed that Dmrt3 neurons are part of sensory-motor circuits that control motor activity, receiving inputs from both proprioceptive sensory neurons and brain areas linked to motor regulation, suggesting these neurons are integral to the classic reflex pathways within the spinal cord.
Investigation Methodology and Findings
- The researchers used a tracing method known as monosynaptic retrograde replication-deficient rabies tracing to analyze the presynaptic inputs to spinal Dmrt3 neurons. This method allowed them to trace the path of signals being sent to these neurons.
- The study established that lumbar Dmrt3 neurons received inputs from both intrasegmental neurons (those within the same segment of the spinal cord), and intersegmental neurons (those from cervical, thoracic, and sacral segments of the spinal cord).
- Among the neurons providing inputs were excitatory V2a interneurons, and likely Renshaw cells, which are characterized by the expression of certain proteins (Chx10 and calbindin respectively).
The Role of Proprioceptive Sensory Neurons
- Proprioceptive sensory neurons of types Ia2, Ia3, and Ib were found to provide inputs to the Dmrt3 neurons. These sensory neurons are known for their role in proprioception, which is our sense of the relative position of body parts and the effort required to move them.
- The study found that these neurons were defined by the expression of certain proteins (calbindin, calretinin, and Brn3c respectively), indicating their role in transmitting sensory information to Dmrt3 neurons.
Brain Inputs to Dmrt3 Neurons
- The findings also presented that Dmrt3 neurons receive inputs from motor-related areas in the brain, including the red nucleus, primary sensory-motor cortex, and pontine nuclei.
- This suggests these neurons have a role in processing sensory information and central commands before providing instructions to motor neurons.
Studying the Role of Dmrt3 Neurons
- The research successfully highlighted the crucial role of Dmrt3 neurons in the control of motor activity and reflex regulation within the spinal cord.
- Gaining a deeper understanding of how these neurons function and interact with sensory and central inputs can aid in developing therapeutic strategies for diseases which affect the motor system, such as Parkinson’s disease or multiple sclerosis.
Cite This Article
APA
Vieillard J, Franck MCM, Hartung S, Jakobsson JET, Ceder MM, Welsh RE, Lagerström MC, Kullander K.
(2022).
Adult spinal Dmrt3 neurons receive direct somatosensory inputs from ipsi- and contralateral primary afferents and from brainstem motor nuclei.
J Comp Neurol, 531(1), 5-24.
https://doi.org/10.1002/cne.25405 Publication
Researcher Affiliations
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Present address: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
MeSH Terms
- Mice
- Animals
- Horses
- Transcription Factors / metabolism
- Zebrafish / metabolism
- Motor Neurons / physiology
- Spinal Cord / metabolism
- Interneurons / metabolism
- Calbindins / metabolism
- Brain Stem / metabolism
Conflict of Interest Statement
The authors declare no competing financial interests.
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