The intrinsic function of a motor system--from ion channels to networks and behavior.
ABSTRACT The forebrain, brainstem and spinal cord contribution to the control of locomotion is reviewed in this article. The lamprey is used as an experimental model since it allows a detailed cellular analysis of the neuronal network underlying locomotion. The focus is on cellular mechanisms that are important for the pattern generation, as well as different types of pre- and postsynaptic modulation. This experimental model is bridging the gap between the molecular and cellular level to the network and behavioral level.
Article: Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2.[show abstract] [hide abstract]
ABSTRACT: Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h(2)≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F(1) hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na(+)/K(+)-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo.PLoS ONE 01/2012; 7(5):e38169. · 4.09 Impact Factor
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ABSTRACT: This paper examines how electrical stimulation of the spinal cord can modulate the output of the central pattern generator (CPG) for locomotion. Application of discrete current pulses to a single spinal segment was shown to affect multiple parameters of an ongoing locomotor pattern in an in vitro spinal cord. For any given stimulus, the effects on frequency, duration, and symmetry of locomotor output were strongly dependent on the phase at which stimulation was applied within the CPG cycle. Additionally, most stimuli had an immediate impact and evinced no effects on subsequent cycles. The most dramatic changes were seen when stimulation was applied during motor bursting: stimuli applied to the ipsilateral spinal hemicord increased the burst length, while stimuli applied to the contralateral spinal hemicord decreased the burst length. Smaller changes were observed when stimulating during delays between motor bursts. Thus, phasic stimulation was shown to influence the behavior of the CPG and spinal locomotion circuits on a cycle-by-cycle basis. This work represents the first step toward our ultimate goal of developing a neuroprosthetic device to restore locomotion after a severe spinal cord injuryIEEE Transactions on Neural Systems and Rehabilitation Engineering 10/2006; · 3.44 Impact Factor
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ABSTRACT: General mechanisms of motor network development have often been examined in the spinal cord because of its relative simplicity when compared to higher parts of the brain. Indeed, most of our current understanding of motor pattern generation comes from work in the lower vertebrate spinal cord. Nevertheless, very little is known about the initial stages of motor network formation and the interplay between genes and electrical activity. Recent research has led to the establishment of the zebrafish as a key model system to study the genetics of neural development. The spinal cord of zebrafish is amenable to optical and electrophysiological analysis of neuronal activity even at the earliest embryonic stages when the network is immature. The combination of physiology and genetics in the same animal model should lead to insights into the basic mechanisms of motor circuit formation. This paper reviews recent work on the development of zebrafish motor activity and discusses them in the context of the current knowledge of embryonic and larval zebrafish spinal cord morphology and physiology.Zebrafish 02/2006; 3(2):173-90. · 3.08 Impact Factor