Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor

We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the &alpha;4 subunit of neuronal nicotinic acetylcholine receptor (nAChR). Mutant mice demonstrate brief nicotine induced dystonia that resembles the clinical events seen in patients with the same mutation. Drug-induced dystonia is more pronounced in female mice, thus our aim was to determine if the S248F mutation changed the properties of fast- and slow-twitch muscle fibres from female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in the brain but not skeletal muscles in normal and mutant mice. Ca2+ and Sr2+ force activation curves were obtained using skinned muscle fibres prepared from slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were found: (1) the (pCa50 - pSr50) value from EDL fibres was smaller in mutant mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr 5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results indicate a shift to slow-twitch characteristics in the mutant. This conclusion is supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest that mutant mice may be having subclinical events or the mutation results in a chronic alteration to muscle neural input.</p

Reply to: “Letter on Discussion of Gait Research”

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173009/1/mds29049.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173009/2/mds29049_am.pd

Using motor imagery to study the neural substrates of dynamic balance

Contains fulltext : 126885.pdf (publisher's version ) (Open Access)This study examines the cerebral structures involved in dynamic balance using a motor imagery (MI) protocol. We recorded cerebral activity with functional magnetic resonance imaging while subjects imagined swaying on a balance board along the sagittal plane to point a laser at target pairs of different sizes (small, large). We used a matched visual imagery (VI) control task and recorded imagery durations during scanning. MI and VI durations were differentially influenced by the sway accuracy requirement, indicating that MI of balance is sensitive to the increased motor control necessary to point at a smaller target. Compared to VI, MI of dynamic balance recruited additional cortical and subcortical portions of the motor system, including frontal cortex, basal ganglia, cerebellum and mesencephalic locomotor region, the latter showing increased effective connectivity with the supplementary motor area. The regions involved in MI of dynamic balance were spatially distinct but contiguous to those involved in MI of gait (Bakker et al., 2008; Snijders et al., 2011; Cremers et al., 2012), in a pattern consistent with existing somatotopic maps of the trunk (for balance) and legs (for gait). These findings validate a novel, quantitative approach for studying the neural control of balance in humans. This approach extends previous reports on MI of static stance (Jahn et al., 2004, 2008), and opens the way for studying gait and balance impairments in patients with neurodegenerative disorders.11 p