MOTOR NEURON-SPECIFIC OVEREXPRESSION OF THE PRESYNAPTIC CHOLINE TRANSPORTER IMPACT ON MOTOR ENDURANCE AND EVOKED MUSCLE ACTIVITY

作者：Lund D; Ruggiero A M; Ferguson S M; Wright J; English B A; Reisz P A; Whitaker S M; Peltier A C; Blakely R D^*

来源：Neuroscience, 2010, 171(4): 1041-1053.

DOI：10.1016/j.neuroscience.2010.09.057

• choline
• transport
• acetylcholine
• transgenic synapse
• neuromuscular

The presynaptic hemicholinium 3 sensitive, high affinity choline transporter (CHT) supplies choline for acetyl choline (ACh) synthesis In mice, a homozygous deletion of CHT (CHT-/-) leads to premature cessation of spontaneous or evoked neuromuscular signaling and is associated with perinatal cyanosis and lethality within 1 h Heterozygous (CHT+/-) mice exhibit diminished brain ACh levels and demonstrate an inability to sustain vigorous motor activity We sought to explore the contribution of CHT gene dosage to motor function in greater detail using transgenic mice where CHT is expressed under control of the motor neuron promoter Hb9 (Hb9 CHT) On a CHT-/- background, the Hb9 CHT transgene conferred mice with the ability to move and breath for a postnatal period of similar to 24 h, thus increasing survival Conversely Hb9 CHT expression on a wild-type background (CHT+/+,Hb9 CHT) leads to an increased capacity for treadmill running compared to wild type littermates Analysis of the stimulated compound muscle action potential (CMAP) in these animals under basal conditions established that CHT+/+,Hb9 CHT mice display an unexpected, bidirectional change, producing either elevated or reduced CMAP amplitude relative to CHT+/+ animals To examine whether these two groups arise from underlying changes in synaptic properties, we used high frequency stimulation of motor axons to assess CMAP recovery kinetics Although CHT+/+, Hb9 CHT mice in the two groups display an equivalent, time dependent reduction in CMAP amplitude, animals with a higher basal CMAP amplitude demonstrate a significantly enhanced rate of recovery To explain our findings, we propose a model

• 出版日期2010-12-29