Noradrenergic modulation of intrinsic and synaptic properties of lumbar motoneurons in the neonatal rat spinal cord

Abstract

Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1), clonidine (α2) and isoproterenol (β) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1), yohimbine (α2) and propranolol (β). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord.

<b>Noradrenergic effects in rat sacral autonomic nucleus using in vitro slice patch-clamp r</b><b>ecordings </b>

“…In addition, we found that NA increased sEPSC through α1 receptors in some populations of regular type neurons. Several studies have addressed the relevance of NAergic modulation of synaptic events in the spinal cord (1,2,5,20,29). In this study, α2 receptor-mediated synaptic inhibition of sEPSC was observed in both types of neurons, consistent with previous reports.…”

“…Further, we showed α1 receptor-mediated increase of sEPSC. This has also been reported in spinal motor neurons (29) and other supraspinal regions such as the nucleus tractus solitaries (14), paraventricular hypothalamic nucleus (3), and cerebral cortex (17). Comparable to the modulation of sEPSC, inhibition of sIPSC was observed mainly in delayed type neurons, and α1 receptor-mediated enhancement of sIPSC was observed in regular type neurons.…”

“…NAergic modulation of neural activities has been studied in other spinal regions (9, 12, 31). As described above, depolarization through α1 receptors was observed in motor neurons (29) and interneurons located in the dorsal horn (10). Hyperpolarization through α2 receptors was observed in the major populations of spinal dorsal horn neurons (24,26).…”

“…Any delays of first firing to current injections were considered as a delayed firing types of neurons, and other cells were considered as regular firing types. In some cases, the recorded neurons were anatomically identified neurons (29,33) and some populations of interneurons (10), whereas it directly hyperpolarizes the majority of spinal dorsal horn neurons (24,26). A number of experiments have shown the involvement of NA in pelvic organ function and have indicated its multiple actions.…”

Origin of Thoracic Spinal Network Activity during Locomotor-Like Activity in the Neonatal Rat

“…Spinal cords were fixed in 4% paraformaldehyde in PBS overnight at 4°C, cryoprotected in 20% sucrose, embedded in OCT Tissue-Tek, frozen, and cut transversely on a cryostat (30 M). The slices were mounted on slides and processed for choline acetyl transferase (ChAT) immunodetection using a goat anti-ChAT antibody (1:100; Millipore) revealed with an Alexa Fluor 488 donkey anti-goat secondary antibody (1:500; Tartas et al, 2010). Images of ChAT-immunopositive cells were acquired using a Nikon AZ100M microscope.…”