title: Quantitative analysis of locomotor defects in neonatal mice lacking proprioceptive feedback.
abstract: Proprioceptive feedback derived from specialized receptors in skeletal muscle is critical in forming an accurate map of limb position in space, and is used by the central nervous system to plan future movements and to determine accuracy of executed movements. Knockout mouse strains for genes expressed by proprioceptive sensory neurons have been generated that result in generalized motor deficits, but these deficits have not been quantitatively characterized. Here we characterize a conditional knockout mouse model wherein proprioceptive sensory neuron synaptic transmission has been blocked by selective ablation of munc18-1, a synaptic vesicle associated protein required for fusion of synaptic vesicles with the plasma membrane. Proprioceptive munc18-1 conditional mutants are impaired in surface righting--a dynamic postural adjustment task--and display several specific deficits in pivoting, an early locomotor behavior. Before the emergence of forward locomotion during postnatal development, animals explore their surroundings through pivoting, or rotating the upper torso around the relatively immobile base of the hind limbs. 3-D kinematic analysis was used to quantitatively describe this pivoting behavior at postnatal days 5 and 8 in control and munc18-1 conditional mutants. Mutant animals also pivot, but demonstrate alterations in movement strategy and in postural placement of the forelimbs during pivoting when compared to controls. In addition, brief forelimb stepping movements associated with pivoting are altered in mutant animals. Step duration and step height are increased in mutant animals. These results underscore the importance of proprioceptive feedback even at early stages in postnatal development.
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Dayton, OH, United States.
authors.forename: Marisela A
authors.initials: MA
authors.lastname: Dallman
authors.forename: David R
authors.initials: DR
authors.lastname: Ladle
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D001696:Biomechanical Phenomena; D025461:Feedback, Physiological / Q000502:physiology*; D005552:Forelimb / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D051938:Munc18 Proteins / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D011187:Posture / Q000502:physiology; D011434:Proprioception / Q000235:genetics* / Q000502:physiology*; D012984:Software; D014741:Video Recording
chemical_list: D051938:Munc18 Proteins; C497938:Stxbp1 protein, mouse
keywords: Behavior; Development; Locomotion; Proprioception
references.citation: Anat Embryol (Berl). 1991;184(2):103-24
references.pmid: 1952098
references.citation: Neuroscience. 1990;35(2):375-475
references.pmid: 2199841
references.citation: Nat Neurosci. 2002 Oct;5(10):946-54
references.pmid: 12352981
references.citation: Trends Neurosci. 1992 Aug;15(8):303-8
references.pmid: 1384200
references.citation: Nat Genet. 1998 Sep;20(1):87-91
references.pmid: 9731539
references.citation: Neuron. 1996 Dec;17(6):1251-64
references.pmid: 8982171
references.citation: Anim Behav. 1975 Nov;23(4):896-920
references.pmid: 1200422
references.citation: Neuroscience. 2003;120(3):733-44
references.pmid: 12895513
references.citation: J Comp Neurol. 2010 Dec 1;518(23):4675-701
references.pmid: 20963823
references.citation: Adv Anat Embryol Cell Biol. 2000;154:iii-ix, 1-145
references.pmid: 10692782
references.citation: J Neurophysiol. 1995 Feb;73(2):820-35
references.pmid: 7760137
references.citation: Pharmacol Biochem Behav. 1990 Aug;36(4):875-81
references.pmid: 2217517
references.citation: Neuroscience. 1995 Oct;68(3):883-92
references.pmid: 8577381
references.citation: Int J Dev Neurosci. 2010 Aug;28(5):359-70
references.pmid: 20406674
references.citation: J Neurosci. 2002 May 1;22(9):3512-9
references.pmid: 11978828
references.citation: J Comp Neurol. 1990 Dec 22;302(4):715-28
references.pmid: 2081815
references.citation: Neuroscience. 1994 Jul;61(1):123-32
references.pmid: 7526265
references.citation: J Neurosci. 2005 Jan 5;25(1):96-107
references.pmid: 15634771
references.citation: Neuroscience. 1988 Nov;27(2):571-96
references.pmid: 3217005
references.citation: Eur J Neurosci. 2004 Aug;20(3):623-34
references.pmid: 15255974
references.citation: Science. 2000 Feb 4;287(5454):864-9
references.pmid: 10657302
references.citation: Cell. 2000 May 26;101(5):485-98
references.pmid: 10850491
references.citation: PLoS One. 2011;6(11):e28137
references.pmid: 22140524
references.citation: PLoS Biol. 2005 May;3(5):e159
references.pmid: 15836427
references.citation: Neuroscience. 2004;127(3):785-96
references.pmid: 15283975
references.citation: J Biol Chem. 2012 Jul 27;287(31):25821-33
references.pmid: 22685295