Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions. In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.

The re-expression of hindlimb locomotion after complete spinal cord injuries (SCIs) is caused by the presence of a spinal central pattern generator (CPG) for locomotion. After partial SCI, however, the role of this spinal CPG in the recovery of hindlimb locomotion in the cat remains mostly unknown. In the present work, we devised a dual-lesion paradigm to determine its possible contribution after partial SCI. After a partial section of the left thoracic segment T10 or T11, cats gradually recovered voluntary quadrupedal locomotion. Then, a complete transection was performed two to three segments more caudally (T13–L1) several weeks after the first partial lesion. Cats that received intensive treadmill training after the partial lesion expressed bilateral hindlimb locomotion within hours of the complete lesion. Untrained cats however showed asymmetrical hindlimb locomotion with the limb on the side of the partial lesion walking well before the other hindlimb. Thus, the complete spinalization revealed that the spinal CPG underwent plastic changes after the partial lesions, which were shaped by locomotor training. Over time, with further treadmill training, the asymmetry disappeared and a bilateral locomotion was reinstated. Therefore, although remnant intact descending pathways must contribute to voluntary goal-oriented locomotion after partial SCI, the recovery and re-expression of the hindlimb locomotor pattern mostly results from intrinsic changes below the lesion in the CPG and afferent inputs.

The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP. In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells.