Alpha-1 Adrenoceptor Agonists Generate a “Fast” NMDA Receptor-Independent Motor Rhythm in the Neonatal Rat Spinal Cord

Abstract

Noradrenaline, a potent activator of rhythmogenic networks in adult mammals has not been reported to produce functional rhythmic patterns in isolated spinal cords of newborn rats. We now show that a "fast" (cycle time: 1-4 s) transient rhythm was induced in sacrococcygeal (SC) and rostral-lumbar spinal segments of the neonatal rat by bath-applied noradrenaline. The fast rhythm was blocked by 1 microM of the alpha1-adrenoceptor antagonist prazosin but not by 1-20 microM of the alpha2-adrenoceptor blocker yohimbine, it could be initiated and maintained by alpha1-adrenoceptor agonists, and it was accompanied by a slow nonlocomotor rhythm. Transection at the lumbosacral junction abolished the fast-thoracolumbar (TL) rhythm while the fast-SC and slow-TL rhythms were unaffected. The N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) abolished the slow- and did not interrupt the fast rhythm. Thus alpha1-adrenoceptor agonists induce an NMDA receptor-independent rhythm in the SC cord and modulate NMDA receptor-dependent rhythmicity in TL segments. Injection of current steps into S(2) and flexor-dominated L(2) motoneurons during the fast rhythm revealed a 20-30% decrease in input-resistance (R(N)), coinciding with contralateral bursting. The R(N) of extensor-dominated L(5) motoneurons did not vary with the fast rhythm. The rhythmic fluctuations of R(N) in L(2) motoneurons were abolished, but the alternating left-right pattern of the fast rhythm was unchanged in midsagittally split TL cords. We suggest that the locomotor generators were not activated during the fast rhythm, that crossed-inhibitory pathways activated by SC projections controlled the rhythmic decrease in R(N) in L(2) motoneurons, and that the alternating pattern of the split TL cord was maintained by excitatory SC projections.

Long and Short Multifunicular Projections of Sacral Neurons Are Activated by Sensory Input to Produce Locomotor Activity in the Absence of Supraspinal Control

“…Recent clinical studies have shown that reactivation of the CPGs in spinal cord injury patients by afferent input is possible, and that it improves the motor function and mobility of patients with incomplete thoracic spinal injury (Wernig et al, 1995;Colombo et al, 2001;Dietz et al, 2002;Dietz and Harkema, 2004;Dietz, 2009). Our findings that stimulation of sacrocaudal afferents (SCAs) in the isolated spinal cord of the neonatal rat is a potent activator of the pattern generating circuitry in the sacral and limb moving segments Delvolvé et al, 2001;Strauss and Lev-Tov, 2003;Gabbay and Lev-Tov, 2004;Blivis et al, 2007; also see Whelan et al, 2000, for the neonatal mouse) enable us to use this preparation to study the functional organization and mechanism of action of the pathways that are involved in sensory-activation of the CPGs, under controlled in vitro conditions. Our previous work revealed that the SCA-induced rhythm is not generated by direct contacts between the stimulated afferents and the hindlimb CPGs, but that it involves synaptic activation of sacral neurons whose axons project to the hindlimb innervating segments of the spinal cord through the white matter funiculi (Strauss and Lev-Tov, 2003;Lev-Tov and O'Donovan, 2009;Lev-Tov et al, 2010).…”

Different effect of locomotor exercise on the homogenate concentration of amino acids and monoamines in the rostral and caudal lumbar segments of the spinal cord in the rat

“…The bath-applied NA induced fast rhythms, which mimicked locomotor activity of the spinal cord in rostro-lumbar and sacrococcygeal, but not in caudal lumbar segments. 33 All these data point to segmentally differentiated capability of spinal networks in generation of locomotor activity, but they also stress an importance of the network in the rostral lumbar segments in the control of locomotion. Our results speak in favor of the latter as long-lasting, moderate locomotor exercise allowed revealing the neurochemical differences between these two parts of the lumbar spinal cord in the adult rat, which may reflect different regulatory mechanisms of the enzymes, which maintain the appropriate levels of neurotransmitters for a long-term function.…”

“…10,32 Several other lines of evidence indicate that in the neonatal rat, the network of interconnected spinal interneurons, which are capable of generating locomotor-like activity, located in the rostral lumbar segments shows greater capacity for rhythmicity than that in other segments. 13,14,28 Noteworthy, Gabbay and Lev-Tov 33 showed that in early developmental period not only rostral lumbar but also sacrococcygeal segments responded differently to NA than to caudal lumbar segments. The bath-applied NA induced fast rhythms, which mimicked locomotor activity of the spinal cord in rostro-lumbar and sacrococcygeal, but not in caudal lumbar segments.…”

Analysis of Rhythmic Patterns Produced by Spinal Neural Networks

“…Recently the effects of genetic manipulations of known groups of spinal neurons on the function of the locomotor rhythm generator have been assayed by monitoring the motor pattern recorded from spinal neurons and the lumbar ventral roots (Gosgnach et al 2006;; see also reviews by Kiehn 2006;Lev-Tov and O'Donovan 2007). This approach offers great promise for dissecting the internal structure of the generator.…”

“…The quantitative analysis of rhythmic patterns produced by the spinal cord is traditionally focused on the frequency and the phase relation between the activities of populations of neurons. The quantitative data are usually extracted from the low-pass filtered or the integrated envelope of rectified rhythmic bursts either manually or semimanually using a computer-based detection of rhythmic waveforms (see Gosgnach et al 2006;). This type of analysis has several inherent problems: it is inaccurate especially when the signals are attenuated after pharmacological treatments, specific lesions, or genetic manipulations and it does not provide quantitative information about the power of the signal or the precise strength of coupling between populations of neurons.…”