Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and its physiological consequences. The somato-dendritic compartments of motoneurons are densely innervated by serotonergic synaptic boutons and several receptors are expressed in the membrane of motoneurons including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C and 5-HT5A. The activation of serotonergic receptors induces a general increase of the excitability of motoneurons through the modulation of several classes of ion channels. 5-HT depolarizes motoneurons towards the threshold for action potentials by inhibiting leak conductances and promoting a hyperpolarization activated cationic current. At the same time, 5-HT increases the firing frequency by inhibiting the small Ca2+ activated K+ conductance (SK) responsible for the medium afterhyperpolarization (AHP) following action potentials. 5-HT also promotes persistent inward currents mediated by voltage sensitive Ca2+ and Na+ conductances, producing a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle spasms and spasticity and hence, impairment of stereotyped motor behaviors such as locomotion, ejaculation and micturition.

Astrocytes participate in neuronal signalling by releasing gliotransmitters in response to neurotransmitters. We investigated if astrocytes from the dorsal horn of the spinal cord of adult red-eared turtles (Trachemys scripta elegans) release GABA in response to glutamatergic receptor activation. For this, we developed a GABA sensor consisting of HEK cells expressing GABA receptors. By positioning the sensor recorded in the whole-cell patch-clamp configuration within the dorsal horn of a spinal cord slice, we could detect GABA in the extracellular space. Puff application of glutamate induced GABA release events with time courses that exceeded the duration of inhibitory postsynaptic currents by one order of magnitude. Because the events were neither affected by extracellular addition of nickel, cadmium and tetrodotoxin nor by removal of Ca , we concluded that they originated from non-neuronal cells. Immunohistochemical staining allowed the detection of GABA in a fraction of dorsal horn astrocytes. The selective stimulation of A∂ and C fibres in a dorsal root filament induced a Ca increase in astrocytes loaded with Oregon Green BAPTA. Finally, chelating Ca in a single astrocyte was sufficient to prevent the GABA release evoked by glutamate. Our results indicate that glutamate triggers the release of GABA from dorsal horn astrocytes with a time course compatible with the integration of sensory inputs.

The axon initial segment (AIS) is a key neuronal compartment because it is responsible for action potential initiation. The local density of Na channels, the biophysical properties of K channels, as well as the length and diameter of the AIS determine the spiking of neurons. These parameters undergo important modifications during development. The development of the AIS is governed by intrinsic mechanisms. In addition, surrounding neuronal networks modify its maturation. As a result, neurons get tuned to particular physiological functions. Neuronal activity also influences the morphology of the mature AIS. When excitatory neurons are hyperactive, their AIS undergo structural changes that decrease their excitability and thereby maintain the activity within a given range. These slow homeostatic regulatory mechanisms occur on a time scale of hours or days. In contrast, the activation of metabotropic receptors modulates the properties of ion channels expressed at the AIS within seconds and consequently produces fast adjustments of neuronal excitability. Recent results suggest that this plasticity plays important roles in physiological functions as diverse as memory formation, hearing, and motor control.

For many years, glial cells from the central nervous system have been considered as support cells involved in the homeostasis of the brain. However, a series of key-findings obtained during the past two decades has put light on unexpected roles for glia and it is getting more and more admitted that glia play an active role in several physiological functions. The discovery that a bidirectional communication takes place between astrocytes (the star shaped glial cell of the brain) and neurons, was a major breakthrough in the field of synaptic physiology. Astrocytes express receptors that get activated by neurotransmitters during synaptic transmission. In turn they release other transmitters - called gliotransmitters - that bind to neuronal receptors and modulate synaptic transmission. This feedback, which led to the concept of the tripartite synapse, has been reported with various transmitters including glutamate, ATP, GABA or serine. In the present review we will focus on astrocytes and review the evidence suggesting and demonstrating their role in motor control. Rhythmic motor behaviors such as locomotion, swimming or chewing are generated by networks of neurons termed central pattern generators (CPG). These networks are highly flexible and adjust the frequency of their output to the external environment. In the case of respiration, the CPG reacts when changes in the pH of the blood occur. The chemosensory control of breathing is ensured by astrocytes, which react to variation of the blood pH by releasing ATP on neurons that in turn adapt the frequency of respiration. In the spinal cord, diverse transmitters such as ATP, adenosine or endocannabinoids modulate the CPG responsible for locomotion. A growing body of evidence suggests that glial cells release some of these molecules. These data suggest that astrocytes play an essential role in motor control and we believe that a range of studies will confirm this view in the near future.

The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. The subiculum receives a high density of fibers originating from the raphe nuclei, suggesting that serotonin (5-HT) modulates subicular neurons. Here we investigated if and how 5-HT modulates the firing pattern of bursting neurons. By combining electrophysiological analysis with pharmacology, optogenetics and calcium imaging, we demonstrate that 5-HT2C receptors reduce bursting activity by inhibiting a low-threshold calcium current mediated by T-type Ca2+ channels in principal cells of the subiculum. In addition, we show that the activation of this novel pathway decreases bursting activity and the occurrence of epileptiform discharges induced in in vitro models for temporal lobe epilepsy (TLE).