Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in the decerebrated rat

ABSTRACTSpinal cord injury (SCI) results in the disruption of supraspinal control of spinal networks and an increase in the relative influence of afferent feedback to sublesional neural networks, both of which contribute to enhancing spinal reflex excitability. Hyperreflexia occurs in ~75% of individuals with chronic SCI and critically hinders functional recovery and quality of life. It is suggested to result from an increase in motoneuronal excitability and a decrease in presynaptic and postsynaptic inhibitory mechanisms. In contrast, locomotor training decreases hyperreflexia by restoring presynaptic inhibition.Primary afferent depolarization (PAD) is a powerful presynaptic inhibitory mechanism that selectively gates primary afferent transmission to spinal neurons to adjust reflex excitability and ensure smooth movement. However, the effect of chronic SCI and step-training on the reorganization of presynaptic inhibition evoked by hindlimb afferents, and the contribution of PAD has never been demonstrated. The objective of this study is to directly measure changes in presynaptic inhibition through dorsal root potentials (DRPs) and its association to plantar H-reflex inhibition. We provide direct evidence that H-reflex hyperexcitability is associated with a decrease in transmission of PAD pathways activated by PBSt afferents after chronic SCI. More precisely, we illustrate that PBSt group I muscle afferents evoke a similar pattern of inhibition onto both L4-DRPs and plantar H-reflexes evoked by the tibial nerve in Control and step-trained animals, but not in chronic SCI rats. These changes are not observed after step-training, suggesting a role for activity-dependent plasticity to regulate PAD pathways activated by flexor muscle group I afferents.Key point summaryPresynaptic inhibition is modulated by supraspinal centers and primary afferents in order to filter sensory information, adjust spinal reflex excitability, and ensure smooth movements.After SCI, the supraspinal control of primary afferent depolarization (PAD) interneurons is disengaged, suggesting an increased role for sensory afferents. While increased H-reflex excitability in spastic individuals indicates a possible decrease in presynaptic inhibition, it remains unclear whether a decrease in sensory-evoked PAD contributes to this effect.We investigated whether the PAD evoked by hindlimb afferents contributes to the change in presynaptic inhibition of the H-reflex in a decerebrated rat preparation. We found that chronic SCI decreases presynaptic inhibition of the plantar H-reflex through a reduction in PAD evoked by PBSt muscle group I afferents.We further found that step-training restored presynaptic inhibition of the plantar H-reflex evoked by PBSt, suggesting the presence of activity-dependent plasticity of PAD pathways activated by flexor muscle group I afferents.

Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats

Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was −60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L7 ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0–120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.

Long-Latency and Voluntary Responses to an Arm Displacement Can Be Rapidly Attenuated By Perturbation Offset

Feedback control of our limbs must account for the unexpected offset of mechanical perturbations. Here we examine the evoked activity of elbow flexor and extensor muscles to torque pulses lasting 22–152 ms and how torque offset impacts activity in the long-latency (45–100 ms) and voluntary epochs (120–180 ms). For each pulse width, we found a significant attenuation of muscle activity ∼30 ms after the offset of torque compared with when the torque was sustained. The brief time between the offset of torque and the attenuation of muscle activity implicates group I afferents acting through a spinal pathway, because this route is the only one fast enough and short enough to be responsible. Moreover, elbow muscle activity in the subsequent 20–45 ms following torque-offset was ∼35% smaller than when the torque was sustained. These results show that a fast spinal process can powerfully attenuate corrective responses of the arm to a torque perturbation.

Sensory Integration in Presynaptic Inhibitory Pathways During Fictive Locomotion in the Cat

The aim of this study is to understand how sensory inputs of different modalities are integrated into spinal cord pathways controlling presynaptic inhibition during locomotion. Primary afferent depolarization (PAD), an estimate of presynaptic inhibition, was recorded intra-axonally in group I afferents ( n = 31) from seven hindlimb muscles in L6–S1 segments during fictive locomotion in the decerebrate cat. PADs were evoked by stimulating alternatively low-threshold afferents from a flexor nerve, a cutaneous nerve and a combination of both. The fictive step cycle was divided in five bins and PADs were averaged in each bin and their amplitude compared. PADs evoked by muscle stimuli alone showed a significant phase-dependent modulation in 20/31 group I afferents. In 12/20 afferents, the cutaneous stimuli alone evoked a phase-dependent modulation of primary afferent hyperpolarization (PAH, n = 9) or of PADs ( n = 3). Combining the two sensory modalities showed that cutaneous volleys could significantly modify the amplitude of PADs evoked by muscle stimuli in at least one part (bin) of the step cycle in 17/31 (55%) of group I afferents. The most common effect (13/17) was a decrease in the PAD amplitude by 35% on average, whereas it was increased by 17% on average in the others (4/17). Moreover, in 8/13 afferents, the PAD reduction was obtained in 4/5 bins i.e., for most of the duration of the step cycle. These effects were seen in group I afferents from all seven muscles. On the other hand, we found that different cutaneous nerves had quite different efficacy; the superficial peroneal (SP) being the most efficient (85% of trials) followed by Saphenous (60%) and caudal sural (44%) nerves. The results indicate that cutaneous interneurons may act, in part, by modulating the transmission in PAD pathways activated by group I muscle afferents. We conclude that cutaneous input, especially from the skin area on the dorsum of the paw (SP), could subtract presynaptic inhibition in some group I afferents during perturbations of stepping (e.g., hitting an obstacle) and could thus adjust the influence of proprioceptive feedback onto motoneuronal excitability.