The role of peripheral afferent inputs and their interactions with serotonin in the control of motoneuron activity
It is known that neural circuitry in the spinal cord below a total transection is almost totally devoid of serotonin. As a consequence of spinal injury rats do not walk spontaneously. However, chronic spinal rats can be induced to perform proper plantar stepping by tail stimulation in the upright posture. Such plantarstepping is altered by removal of afferent feedback from the paws showing that sensory feedback from the foot facilitates the spinal central pattern generator (CPG) for locomotion when serotonergic innervation is missing. Although spinal rats can be induced to walk in the upright posture, they do not display recovery of quadrupedal locomotion in the horizontal posture typical for progression in rodents. Our data show that activation of 5-HT2A and 5-HT7/1A receptors using their agonists facilitates plantar stepping in the horizontal posture but interferes with upright stepping in paraplegic rats. In our next investigations we found that in intact adult freely moving rats intrathecal application of the selective 5-HT7 antagonist SB269970 induces hindlimb paralysis. This occurs without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra- and inter-limb coordination during locomotion in intact rats but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR) in adult rat decerebrate preparations. During the recovery period, after transient blocking of MLR evoked fictive locomotion, the amplitude and frequency of rhythmic activity was reduced. The lack of effects on coordination by SB269970 application in paralyzed decerebrate rats with no afferent feedback indicates a critical role of 5-HT7 receptor mediated control of sensory pathways during locomotor activity. Our data show that for optimal coordinated locomotor movements in adult rats, in addition to activation of the serotonergic system, a potent afferent feedback from the foot seems to be necessary FINANCIAL SUPPORT: This work has been supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‑Curie grant agreement no 665735 (Bio4Med) and by the funding from Polish Ministry of Science and Higher Education within 2016–2020 funds for the implementation of international projects (agreement no 3548/H2020/COFUND/2016/2).