The human central nervous system transmits common synaptic inputs to distinct motor neuron pools during non-synergistic digit actions.

KEY POINTS: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un-matched forces in different directions. We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control. The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire. ABSTRACT: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. Here we quantify the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles in humans during voluntary contractions. To remove confounds associated with previous studies, we used a task that required the two hand muscles to exert matched or un-matched forces in different directions. Despite the force production task consisting of uncommon digit force coordination patterns, we found that synaptic input to motor neurons is shared across all frequency bands, reflecting cortical and spinal inputs associated with force control. The coherence between discharge timings of the two pools of motor neurons was significant at the delta (0-5 Hz), alpha (5-15 Hz) and beta (15-35 Hz) bands (P < 0.05). These results suggest that correlated input to motor neurons of two hand muscles can occur even during tasks not belonging to a common behavioural repertoire and despite lack of common innervation. Moreover, we show that the extraction of activity from motor neurons during voluntary force control removes cross-talk associated with global EMG recordings, thus allowing direct in vivo interrogation of spinal motor neuron activity.

PainDETECT: a suitable screening tool for neuropathic pain in patients with painful post-traumatic trigeminal nerve injuries?

The PainDETECT questionnaire (PD-Q), originally developed and validated in a multicentre study of neuropathic pain (NeP) patients with back pain, is increasingly being applied to other pain conditions. The present study assessed whether the PD-Q would be a suitable screening tool for detecting NeP in patients with post-traumatic inferior alveolar nerve injury (IANI) and lingual nerve injury (LNI). A prospective cohort of patients with clinically diagnosed neuropathy was given the PD-Q at their clinic appointment, or it was sent to them after their consultation. Eighty-nine patients (IANI = 56, LNI = 33) were included in the study, 75 of whom suffered from painful neuropathy. Of the patients who completed the questionnaire fully (n = 56), allowing a summary score to be calculated, 34% were classified as having 'likely NeP' according to the PD-Q; 41% of patients scored in the uncertain classification range and the remaining quarter in the 'likely nociceptive' classification. There was a significant association between PD-Q scores and pain intensity levels across the sample, with those classified as likely NeP reporting high levels of pain. The results suggest that the PD-Q in its current format is not a suitable screening tool for NeP associated with IANI or LNI.

Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development.

The development of glutamatergic synapses involves changes in the number and type of receptors present at the postsynaptic density. To elucidate molecular mechanisms underlying these changes, we combine in utero electroporation of constructs that alter the molecular composition of developing synapses with dual whole-cell electrophysiology to examine synaptic transmission during two distinct developmental stages. We find that SAP102 mediates synaptic trafficking of AMPA and NMDA receptors during synaptogenesis. Surprisingly, after synaptogenesis, PSD-95 assumes the functions of SAP102 and is necessary for two aspects of synapse maturation: the developmental increase in AMPA receptor transmission and replacement of NR2B-NMDARs with NR2A-NMDARs. In PSD-95/PSD-93 double-KO mice, the maturational replacement of NR2B- with NR2A-NMDARs fails to occur, and PSD-95 expression fully rescues this deficit. This study demonstrates that SAP102 and PSD-95 regulate the synaptic trafficking of distinct glutamate receptor subtypes at different developmental stages, thereby playing necessary roles in excitatory synapse development.