The present study has investigated the rhythmic properties of spinal networks in the neonatal rat spinal cord in vitro, by means of intracellular recordings from single motoneurons and extracellular recordings from ventral roots. The occurrence and basic characteristics of an alternating locomotor-like pattern, triggered by stimulating afferent dorsal root fibers, was described, suggesting that sensory inputs from the periphery can activate the spinal locomotor network. It was proposed that activation of the locomotor CPG could occur via an increase in extracellular K+ and network neuron depolarization. Furthermore, it was demonstrated that spinal networks could generate rhythms exhibiting a variety of different properties in terms of phase, frequency, and duration of patterns. Due to the importance of inhibitory transmission in shaping such rhythmic patterns, and the complex role that glycine and GABA seem to have in the developing central nervous system, the nature and function of er mediated synaptic transmission was investigated on motoneurons. To this aim, the glycinergic and GABAergic recurrent postsysnaptic potential (PSP) mediated by Renshaw cells was used to assess its impact on excitatory synaptic inputs from dorsal afferent fibers. Despite its depolarizing nature, the recurrent PSP consistently inhibited synaptic excitation of lumbar motoneurons. Different patterns of rhythmic activity were obtained by activating certain classes of metabotropic receptors present in the spinal cord. In particular, tachykinin NK3 receptors could trigger neuronal bursting, which outlasted the stimulus and appeared predominantly with alternation at segmental level and synchronous coupling between ipsilateral motor pools. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory PSP recorded from motoneurons, indicating the possibility that fully alternating pattern generation by the CPG was partly impaired due to a decrease in the efficacy of inhibition. Nevertheless, NK3 receptor activation could facilitate fictive locomotor patterns, since they could operate synergistically with NMDA and 5-HT to trigger fully alternating locomotor-like rhythms. Furthermore, NK3 receptor antagonism disrupted NMDA and 5-HT induced fictive locomotion. Activation of glutamate metabotropic receptors elicited a wide range of effects. Group I receptors mediated depolarization and onset of oscillatory activity (via the subclasses mGluRl and 5, respectively), which usually appeared synchronously at homosegmental and homolateral level. This type of rhythm represented another example of pattern that spinal cord networks could generate in addition to previously reported ones. While the role of group I metabotropic glutamate receptors in fictive locomotion was limited, they seemed to participate in regulating disinhibited rhythm, i.e. bursting induced by block of GABA and glycine receptors. In addition to an excitatory effect, group I receptors also reduced reflex responses, at least partly via facilitation of endogenous glycine transmission. Group II and III metabotropic glutamate receptors, on the other hand, were always inhibitory on spinal neurons and their bursting behavior. Experiments performed with selective agonists and antagonists indicated that group II and III receptors could modulate, and were involved in controlling, the duration and frequency of disinhibited bursts. Thus, the present study broadened our current understanding of the rhythmic patterns generated by spinal networks and identified certain forms of oscillatory behavior as induced by activation of selective classes of transmitter receptors.
|Titolo:||Mechanisms controlling rhythmicity in the neonatal rat spinal cord in vitro|
|Data di pubblicazione:||25-ott-2002|
|Appare nelle tipologie:||8.1 PhD thesis|