Abstract
Spinal neuronal networks are essential for motor function. They are involved in the integration of sensory inputs and the generation of rhythmic motor outputs. They continuously adapt their activity to the internal state of the organism and to the environment. This plasticity can be provided by different neuromodulators. These substances are usually thought of being released by dedicated neurons. However, in other networks from the central nervous system synaptic transmission is also modulated by transmitters released from astrocytes. The star-shaped glial cell responds to neurotransmitters by releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice. Neurons responded to electrical stimulation by monosynaptic EPSCs (excitatory monosynaptic postsynaptic currents). We used mice expressing the enhanced green fluorescent protein under the promoter of the glial fibrillary acidic protein to identify astrocytes. Chelating calcium with BAPTA in a single neighboring astrocyte increased the amplitude of synaptic currents. In contrast, when we selectively stimulated astrocytes by activating PAR-1 receptors with the peptide TFLLR, the amplitude of EPSCs evoked by a paired stimulation protocol was reduced. The paired-pulse ratio was increased, suggesting an inhibition occurring at the presynaptic side of synapses. In the presence of blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking adenosine A1 receptors with 8-Cyclopentyl-1,3-dipropylxanthine prevented it. Altogether our results show that ventral horn astrocytes are responsible for a tonic and a phasic inhibition of excitatory synaptic transmission by releasing ATP, which gets converted into adenosine that binds to inhibitory presynaptic A1 receptors.
Highlights
Neuronal networks located in the ventral horns of the spinal cord are essential for motor control (Kjaerulff and Kiehn, 1996; Prut and Perlmutter, 2003; Lanuza et al, 2004; Dai et al, 2005; Brocard et al, 2010; Mui et al, 2012)
Our study suggests that astrocytes located in the ventral horn of the spinal cord induce both tonic and phasic presynaptic inhibition of excitatory synaptic transmission
Our results indicate that extracellular ectonucleotidases convert adenosine triphosphate (ATP) released by astrocytes into adenosine, which binds to A1 inhibitory receptors located on the presynaptic side of excitatory synapses (Figure 8)
Summary
Neuronal networks located in the ventral horns of the spinal cord are essential for motor control (Kjaerulff and Kiehn, 1996; Prut and Perlmutter, 2003; Lanuza et al, 2004; Dai et al, 2005; Brocard et al, 2010; Mui et al, 2012). In agreement, (Taccola et al, 2012) and (Brockhaus and Ballanyi, 2000) showed that A1 receptor activation depresses bicuculline-evoked seizure-like bursting in newborn rat spinal cords. In other systems such as the hippocampus or the cerebellum, the activation of presynaptic A1 receptors decreases neurotransmitter release by inhibiting Ca2+ channels (Hollins and Stone, 1980; Wu and Saggau, 1994; Zhang et al, 2003)
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