Monoaminergic modulation in spinal reflex pathways from group I afferents

Abstract

Serotonin and noradrenaline are known to play an important part in modulation of spinal neuronal networks. Group I muscle afferents mediate information on dynamic changes of muscle length and tension, and modulation of actions from these afferents could be of importance for the execution of movements. However, previous studies revealed inconsistent modulatory actions by monoamines on synaptic actions of these afferents. The main aim of this thesis was to reinvestigate this problem by first examining whether group I evoked activation of spinal interneurones and ascending tract neurones is modulated by serotonin and noradrenaline and, if so, to study what membrane receptors might be involved in mediating this effect. Thirdly, we compared modulatory effects on synaptic actions of different afferents to the same neurone, in order to examine if these effects are general or apply only to specific input. Finally, experiments were made to investigate if monoaminergic actions act on the target neurones are mediated only via volume transmission or if some actions may be mediated by direct synaptic action.The study focused on monosynaptic actions of group I afferents on individual neurones of four spinal neuronal populations, all of which were located in lumbar segments. They were recorded from in deeply anaesthetised cats. Effects of serotonin and noradrenaline as well as of receptor agonists applied locally by ionophoresis were studied by comparing changes in monosynaptic responses to afferent nerve stimulation before, during and after drug application.Transmission from group I afferents was facilitated by both serotonin and noradrenaline in all the investigated populations. Effects of different receptor agonists were tested on ventral spinocerebellar tract neurones and some agonists were found to have depressive actions, indicating that different receptors contribute to the modulation. In interneurones co-excited by group I and II afferents the effects on group I afferents were facilitatory whereas effects on group II afferents to these neurones were either facilitatory or depressive, resulting in opposite effects of serotonin and noradrenaline on some of these neurones.Neurones of one population, the ventral spinal spinocerebellar tract neurones, were labelled intracellularly with rhodamine dextran or horseradish-peroxidase. They were examined using confocal and electron microscopy for presence of contacts of immunoreactive monoaminergic fibres. The morphological analysis showed that both serotonin and noradrenaline fibres form close appositions with somata and dendrites of these neurones, and that some of the serotoninergic boutons make direct synapses with these neurones. The results of these studies show that group I evoked activation of spinal interneurones and ascending tract neurones is modulated in a highly selective manner, both as regards the type of afferent and the involvement of different membrane receptors. In addition, the evidence that serotoninergic varicosities make synaptic contacts with ventral spinocerebellar tract neurons indicates the possibility of modulation of information from primary afferents to the cerebellum and thereby adjusting the cerebellar integrating functions depending on the demands in a given situation.