Behavioural Brain Research 178 (2007) 1–9 Research report Effect of precocious locomotor activity on the development of motoneurones and motor units of slow and fast muscles in rat J. Sanusi a,d , U. Slawi´ nska b,∗ , R. Navarrete c , G. Vrbov´ a a a Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK b Laboratory of Neuromuscular Plasticity, Department of Neurophysiology, Nencki Institute of Experimental Biology, Warsaw, Poland c Division of Neuroscience and Mental Health, Department of Cellular & Molecular Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK d Department of Anatomy, University of Malaya, 50603 Kuala Lumpur, Malaysia Received 12 October 2006; received in revised form 23 November 2006; accepted 24 November 2006 Available online 19 December 2006 Abstract We have investigated the effect of precociously increasing locomotor activity during early postnatal development by daily treatment with the monoaminergic precursor L-DOPA on the survival of motoneurones supplying the slow soleus (SOL) muscle and the fast, tibialis anterior (TA) and extensor digitorum longus (EDL) muscles as well as the contractile and histochemical properties of these muscles. L-DOPA treatment resulted in a significant loss of motoneurones to the slow SOL muscle, but not to the fast TA and EDL muscles. Moreover, motoneurones to fast muscles also die as when exposed to increased activity in early life, if their axons are repeatedly injured. The loss of normal soleus motoneurones was accompanied by an increase in force of the remaining motor units and sprouting of the surviving axons suggesting a remodelling of motor unit organisation. The time to peak contraction of both SOL and EDL muscles from L-DOPA treated rats was prolonged at 8 weeks of age. At 4 weeks the soleus muscles of the L-DOPA treated animal developed more tension than the saline treated one. This difference between the two groups did not persist and by 8 weeks of age the muscle weight and tetanic tension from either group were not significantly different from control animals. The present study shows that early transient, precocious locomotor activity induced by L-DOPA is damaging to normal soleus but not to normal EDL/TA motoneurones. © 2006 Elsevier B.V. All rights reserved. Keywords: Neuromuscular activity; L-DOPA; Muscle; Motoneurone; Motor unit; Development 1. Introduction Motoneurone activity patterns play an important role in the development and plasticity of the motor unit. In adults, the phys- iological and biochemical properties of muscle fibres belonging to the same motor unit are similar, and are adapted to the func- tional demands imposed upon them by the motoneurone that supplies them. During development, a dynamic matching takes place between the motoneurones and their associated muscle fibres that result in generation of motor unit anatomical and functional diversity (for review see Ref. [20]). In neonatal rodents, motor units are large and have overlap- ping territories as each muscle fibre is innervated by several ∗ Corresponding author. Tel.: +48 22 5892305; fax: +48 22 8225342. E-mail address: u.slawinska@nencki.gov.pl (U. Slawi´ nska). axons from different motoneurones. The establishment of motor unit architecture, where only one axonal branch innervates a single muscle fibre is achieved by elimination of polyneuronal innervation and is an activity-dependent process [1,21,24]. In the rat, the differentiation of the activity patterns of motoneurones supplying slow and fast hindlimb muscles takes place during the first 3 postnatal weeks associated with the development of postural and locomotor functions [1,19,32]. Neonatal rats are unable to produce coordinated locomotor activ- ity and the emergence of quadrupedal locomotion during the second postnatal week depends on the functional and neuro- chemical maturation of descending pathways associated with postural functions [30]. There is considerable evidence based on studies in adult animals that descending catecholaminergic and serotonergic pathways are involved in controlling the spinal interneuronal networks which generate locomotion ([2,5,6], for review see Ref. [25]). 0166-4328/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2006.11.040