5-HT2 receptor antagonism reduces human motoneuron output to antidromic activation but not to stimulation of corticospinal axons

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast-acting excitatory ionotropic inputs. Serotonin (5-HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5-HT increases motoneuron excitability by activating 5-HT2 receptors on the somato-dendritic compartment. In the current study, we examined how antagonism of the 5-HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5-HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double-blinded, placebo-controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley to motoneurons to elicit cervicomedullary motor evoked potentials (CMEPs) in the surface electromyography (EMG) signal of the resting biceps brachii. Likewise, electrical peripheral nerve stimulation was used to generate antidromic spikes in motoneurons and cause recurrent discharges, which were recorded with surface EMG as F-waves in a resting hand muscle. Compared with placebo, we found that 5-HT2 antagonism reduced the amplitude and persistence of F-waves but did not affect CMEP amplitude. 5-HT2 antagonism also reduced maximal contraction strength. The reduced recurrent discharge of motoneurons with 5-HT2 antagonism suggests that 5-HT2 receptors modulate the electrical properties of the initial segment or soma to promote excitability. Conversely, as cyproheptadine did not affect motoneuron excitability to brief synaptic input, but affected maximal contractions requiring sustained input, it seems likely that the 5-HT2-mediated amplification of synaptic input at motoneuron dendrites is functionally significant only when excitatory input activates persistent inward currents

Accreting Pulsars: Mixing-up Accretion Phases in Transitional Systems

In the last 20 years our understanding of the millisecond pulsar (MSP) population changed dramatically. Thanks to RXTE, we discovered that neutron stars in LMXBs spins at 200-750 Hz frequencies, and indirectly confirmed the recycling scenario, according to which neutron stars are spun up to ms periods during the LMXB-phase. In the meantime, the continuous discovery of rotation-powered MSPs in binary systems in the radio and gamma-ray band (mainly with the Fermi LAT) allowed us to classify these sources into two "spiders" populations, depending on the mass of their companion stars: Black Widow, with very low-mass companion stars, and Redbacks, with larger companions possibly filling their Roche lobes but without accretion. It was soon regained that MSPs in short orbital period LMXBs are the progenitors of the spider populations of rotation-powered MSPs, although a direct link between accretion- and rotation-powered MSPs was still missing. In 2013 XMM-Newton spotted the X-ray outburst of a new accreting MSP (IGR J18245-2452) in a source that was previously classified as a radio MSP. Follow up observations of the source when it went back to X-ray quiescence showed that it was able to swing between accretion- to rotation-powered pulsations in a relatively short timescale (few days), promoting this source as the direct link between the LMXB and the radio MSP phases. Following discoveries showed that there exists a bunch of sources, which alternates X-ray activity phases, showing X-ray pulsations, to radio-loud phases, showing radio pulsations, establishing a new class of MSPs: the Transitional MSP. In this review we describe these exciting discoveries and the properties of accreting and transitional MSPs, highlighting what we know and what we have still to learn about in order to fully understand the (sometime puzzling) behavior of these systems and their evolutive connection (abridged)