TY  - JOUR
AU  - Nascimento, Filipe
AU  - Özyurt, M Görkem
AU  - Halablab, Kareen
AU  - Bhumbra, Gardave Singh
AU  - Caron, Guillaume
AU  - Bączyk, Marcin
AU  - Zytnicki, Daniel
AU  - Manuel, Marin
AU  - Roselli, Francesco
AU  - Brownstone, Rob
AU  - Beato, Marco
TI  - Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration.
JO  - Cell reports
VL  - 43
IS  - 12
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2024-01426
SP  - 115046
PY  - 2024
AB  - In many neurological conditions, early-stage neural circuit adaptation preserves relatively normal behavior. In some diseases, spinal motoneurons progressively degenerate yet movement remains initially preserved. This study investigates whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we find that, early in the disease, neurotransmission in a key pre-motor circuit, the recurrent inhibition mediated by Renshaw cells, is reduced by half due to impaired quantal size associated with decreased glycine receptor density. This impairment is specific and not a widespread feature of spinal inhibitory circuits. Furthermore, it recovers at later stages of disease. Additionally, an increased probability of release from proprioceptive afferents leads to increased monosynaptic excitation of motoneurons. We reveal that, in this motoneuron degenerative condition, spinal microcircuits undergo specific multiphasic homeostatic compensations that may contribute to preservation of force output.
KW  - Animals
KW  - Motor Neurons: metabolism
KW  - Motor Neurons: pathology
KW  - Mice
KW  - Homeostasis
KW  - Disease Models, Animal
KW  - Spinal Cord: pathology
KW  - Spinal Cord: metabolism
KW  - Synaptic Transmission: physiology
KW  - Receptors, Glycine: metabolism
KW  - Nerve Degeneration: pathology
KW  - Mice, Inbred C57BL
KW  - Renshaw Cells: metabolism
KW  - ALS (Other)
KW  - CP: Cell biology (Other)
KW  - CP: Neuroscience (Other)
KW  - Renshaw cells (Other)
KW  - electrophysiology (Other)
KW  - glycine receptors (Other)
KW  - motoneurons (Other)
KW  - motor control (Other)
KW  - quantal analysis (Other)
KW  - sensory afferents (Other)
KW  - spinal cord (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39656589
DO  - DOI:10.1016/j.celrep.2024.115046
UR  - https://pub.dzne.de/record/273977
ER  -