Preservation of VGLUT1 synapses on ventral calbindin-immunoreactive interneurons and normal locomotor function in a mouse model of spinal muscular atrophy
| Autor: | Dvir Blivis, Wenfang Liu, Vatsala Thirumalai, Swetha Birineni, Rachel M. Behrend, Michael J. O'Donovan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Calbindins
Physiology Vesicular Acetylcholine Transport Proteins Muscle spindle Population Biology Inhibitory postsynaptic potential Calbindin Muscular Atrophy Spinal Mice S100 Calcium Binding Protein G Interneurons Vesicular acetylcholine transporter medicine Animals education Motor Neurons education.field_of_study Renshaw cell musculoskeletal neural and ocular physiology General Neuroscience Articles Spinal muscular atrophy Spinal cord medicine.disease Survival of Motor Neuron 1 Protein Cholinergic Neurons Mice Mutant Strains Disease Models Animal medicine.anatomical_structure Spinal Cord nervous system Synapses Vesicular Glutamate Transport Protein 1 Neuroscience Locomotion |
| Zdroj: | Journal of Neurophysiology. 109:702-710 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.00601.2012 |
| Popis: | Dysfunction in sensorimotor synapses is one of the earliest pathological changes observed in a mouse model [spinal muscular atrophy (SMA)Δ7] of spinal muscular atrophy. Here, we examined the density of proprioceptive and cholinergic synapses on calbindin-immunoreactive interneurons ventral to the lateral motor column. This population includes inhibitory Renshaw interneurons that are known to receive synaptic input from muscle spindle afferents and from motoneurons. At postnatal day (P)13, near the end stage of the disease, the somatic area of calbindin+ neurons in the L1/L2 and L5/L6 segments was reduced in SMAΔ7 mice compared with controls. In addition, the number and density of terminals expressing the glutamate vesicular transporter (VGLUT1) and the vesicular acetylcholine transporter (VAChT) were increased on calbindin+ cells in the L1-L2 but not in the L5-L6 segments of SMAΔ7 mice. In addition, the isolated spinal cord of SMA mice was able to generate locomotor-like activity at P4-P6 in the presence of a drug cocktail or in response to dorsal root stimulation. These results argue against a generalized loss of proprioceptive input to spinal circuits in SMA and suggest that the loss of proprioceptive synapses on motoneurons may be secondary to motoneuron pathology. The increased number of VGLUT1+ and VAChT+ synapses on calbindin+ neurons in the L1/L2 segments may be the result of homeostatic mechanisms. Finally, we have shown that abnormal locomotor network function is unlikely to account for the motor deficits observed in SMA mice at P4–6. |
| Databáze: | OpenAIRE |
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