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The nucleus of the solitary tract (NTS) receives viscerosensory information from the vagus nerve to regulate diverse homeostatic reflex functions. The NTS projects to a wide network of other brain regions, including the paraventricular nucleus of the hypothalamus (PVN). Here we examined the synaptic characteristics of primary afferent pathways to PVN-projecting NTS neurons in rat brainstem slices. Expression of the Transient Receptor Potential Vanilloid receptor (TRPV1+) distinguishes C-fiber afferents within the solitary tract (ST) from A-fibers (TRPV1−). We used resiniferatoxin (RTX), a TRPV1 agonist, to differentiate the two. The variability in the latency (jitter) of evoked excitatory postsynaptic currents (ST-EPSCs) distinguished monosynaptic from polysynaptic ST-EPSCs. Rhodamine injected into PVN was retrogradely transported to identify PVN-projecting NTS neurons within brainstem slices. Graded shocks to the ST elicited all-or-none EPSCs in rhodamine-positive NTS neurons with latencies that had either low jitter (200 μs - polysynaptic inputs) or both. RTX blocked ST-evoked TRPV1+ EPSCs whether mono- or polysynaptic. Most PVN-projecting NTS neurons (17/21 neurons) had at least one input polysynaptically connected to the ST. Compared to unlabeled NTS neurons, PVN-projecting NTS neurons were more likely to receive indirect inputs and be higher order. Surprisingly, sEPSC rates for PVN-projecting neurons were double that of unlabeled NTS neurons. The ST synaptic responses for PVN-projecting NTS neurons were either all TRPV1+ or all TRPV1−, including neurons that received both direct and indirect inputs. Overall, PVN-projecting NTS neurons received direct and indirect vagal afferent information with strict segregation regarding TRPV1 expression.

Vagus nerve stimulation (VNS) treats patients with drug-resistant epilepsy, depression and heart failure, but the mechanisms responsible are uncertain. The mild stimulus intensities used in chronic VNS suggest activation of myelinated primary visceral afferents projecting to the nucleus of the solitary tract (NTS). Here, we monitored the activity of second and higher order NTS neurons in response to peripheral vagal activation using therapeutic VNS criteria. A bipolar stimulating electrode activated the left cervical vagus nerve, and stereotaxically placed single tungsten electrodes recorded unit activity from the left caudomedial NTS of chloralose-anaesthetized rats. High-intensity single electrical stimuli established vagal afferent conduction velocity (myelinated A-type or unmyelinated C-type) as well as synaptic order (second vs. higher order using paired electrical stimuli) for inputs to single NTS neurons. Then, VNS treatment was applied. A mid-collicular knife cut (KC) divided the brainstem from all supramedullary regions to determine their contribution to NTS activity. Our chief findings indicate that the KC reduced basal spontaneous activity of second-order NTS neurons receiving myelinated vagal input by 85%. In these neurons, acute VNS increased activity similarly in Control and KC animals. Interestingly, the KC interrupted VNS activation of higher order NTS neurons and second-order NTS neurons receiving unmyelinated vagal input, indicating that supramedullary descending projections to NTS are needed to amplify the peripheral neuronal signal from VNS. The present study begins to define the pathways activated during VNS and will help to better identify the central nervous system contributions to the therapeutic benefits of VNS therapy. KEY POINTS: Vagus nerve stimulation is routinely used in the clinic to treat epilepsy and depression, despite our uncertainty about how this treatment works. For this study, the connections between the nucleus of the solitary tract (NTS) and the higher brain regions were severed to learn more about their contribution to activity of these neurons during stimulation. Severing these brain connections reduced baseline activity as well as reducing stimulation-induced activation for NTS neurons receiving myelinated vagal input. Higher brain regions play a significant role in maintaining both normal activity in NTS and indirect mechanisms of enhancing NTS neuronal activity during vagus nerve stimulation.

Rationale Spinal cord injury (SCI) may induce significant respiratory muscle weakness and paralysis, which in turn may cause a patient to require ventilator support. Central nervous system alterations can also exacerbate local inflammatory responses with immune cell infiltration leading to additional risk of inflammation at the injury site. Although mechanical ventilation is the traditional treatment for respiratory insufficiency, evidence has shown that it may directly affect distant organs through systemic inflammation. Objectives This study aimed to better understand the impact of invasive mechanical ventilation on local spinal cord inflammatory responses following cervical or thoracic SCI. Methods Five groups of female Sprague-Dawley rats were anesthetised for 24 h. Three groups received mechanical ventilation: seven rats without SCI, seven rats with cervical injury (C4-C5), and seven rats with thoracic injury (T10); whereas, two groups were non-ventilated: six rats without SCI; and six rats with thoracic injury (T10). Changes in inflammatory responses were determined in the spinal cord tissues collected at the local site of injury. Cytokines were measured using ELISA. Main results SCI induced local pro-inflammatory cytokine IL-6 expression for all groups. Mechanical ventilation also had effects on pro-inflammatory cytokines and independently increased TNF-α and decreased IL-1β levels in the spinal cords of anesthetized rats. Conclusion These data provide the first evidence that mechanical ventilation contributes to local inflammation after SCI and in the absence of direct tissue injury.

Nerve regeneration and functional recovery are often incomplete after peripheral neurotmetic lesion. Atorvastatin has been shown to be neuroprotective after transient ischaemia or traumatic injury. The aim of this study was to establish if systemic administration of Atorvastatin could improve functional muscle reinnervation after complete sciatic nerve section. Sixteen female Sprague-Dawley rats were used in this study. After a complete right sciatic nerve section, end-to-end microsuture repair was performed and fibrin glue was added. Three groups were studied: (1) sutures (S) + fibrin glue (F) only + saline administration for 14 days; (2) S+F+Atorvastatin administration for 14 days; and (3) uninjured nerve. Five months later, the sciatic nerve and the gastrocnemius muscle were isolated to perform in vivo electrophysiological measurements. Better kinematics was observed in atorvastatin-treated rats 5 months after its administration. Indeed, a larger excursion of the hip-ankle-toe angle during walking was observed. This effect was associated with the preservation of electromyographic activity (2.91 mV vs 0.77 mV) and maximal muscle force (85.1 g vs 28.6 g) on stimulation of the proximal nerve section. Five months after a neurotmetic lesion, the recovery is incomplete when using suture and fibrin glue only. Furthermore, the systemic administration of Atorvastatin for 14 days after lesion was beneficial in improving locomotion capability associated with the re-establishment of muscle strength and EMG activity.

Mechanical ventilation (MV) is widely used in spinal injury patients to compensate for respiratory muscle failure. MV is known to induce lung inflammation, while spinal cord injury (SCI) is known to contribute to local inflammatory response. Interaction between MV and SCI was evaluated in order to assess the impact it may have on the pulmonary inflammatory profile. Sprague Dawley rats were anesthetized for 24 h and randomized to receive either MV or not. The MV group included C4–C5 SCI, T10 SCI and uninjured animals. The nonventilated (NV) group included T10 SCI and uninjured animals. Inflammatory cytokine profile, inflammation related to the SCI level, and oxidative stress mediators were measured in the bronchoalveolar lavage (BAL). The cytokine profile in BAL of MV animals showed increased levels of TNF‐ α , IL‐1 β , IL‐6 and a decrease in IL‐10 ( P = 0.007) compared to the NV group. SCI did not modify IL‐6 and IL‐10 levels either in the MV or the NV groups, but cervical injury induced a decrease in IL‐1 β levels in MV animals. Cervical injury also reduced MV‐induced pulmonary oxidative stress responses by decreasing isoprostane levels while increasing heme oxygenase‐1 level. The thoracic SCI in NV animals increased M‐CSF expression and promoted antioxidant pulmonary responses with low isoprostane and high heme oxygenase‐1 levels. SCI shows a positive impact on MV‐induced pulmonary inflammation, modulating specific lung immune and oxidative stress responses. Inflammation induced by MV and SCI interact closely and may have strong clinical implications since effective treatment of ventilated SCI patients may amplify pulmonary biotrauma.

Since the Kalman filter and Monte Carlo techniques, much theoretical work has been put into the development of signal deconvolution tools. Among recent developments taking place in neuroscience are Dynamic Expectation Maximization, Generalized Filtering and the Cubature Kalman Filter. While there are exciting prospects to use these tools for Dynamic Causal Modeling and other analyses of networks, there has been comparatively little work to validate the algorithms on controlled experimental data. In this work, the latest evolution of these tools, the square-root cubature Kalman smoother (SCKS), is tested for its effectiveness on multimodal neurovascular data. Multispectral intrinsic optical imaging and electrophysiological measurements of Wistar rats are used in combination with somatosensory stimulation. The Buxton–Friston (B–F) balloon model is then deconvolved with the SCKS algorithm to obtain the estimated neuronal inputs u ( t ) from the hemodynamic measurements (flow, oxy- and deoxygenated hemoglobin). Results The estimated neuronal inputs are compared to the stimulation protocol and a sensitivity and specificity analysis is carried out. SCKS succeeds in recovering most of the stimulations. Next, the estimated inputs are compared to actual measures of neuronal activity: local field potentials (LFPs) and multiunit activity (MUA). Good sensitivity of the technique is obtained with both LFPs and MUA over the whole recordings, with the area of the ROC curves favoring LFPs. A weak correlation between SCKS estimated inputs and LFPs is found outside stimulation periods, significant at one standard deviation. Finally, the accuracy of state reconstructions is studied and SCKS reconstructed states are highly concordant with measured states.

Hindlimb motoneuron excitability was compared among exercise-trained (E), sedentary (S), and spinal cord transected (T) Sprague-Dawley rats by examining the slope of the frequency-current (F/I) relationship with standard intracellular recording techniques in rats anesthetized with ketamine-xylazine. The T group included spinal transected and spinal isolated rats; the E animals were either spontaneously active (exercise wheel) or treadmill trained; and rats in the S group were housed in pairs. An analysis of motoneuron initial [1st interspike interval (ISI)], early (mean of 1st three ISIs), and steady-state (mean of last 3 ISIs) discharge rate slopes resulting from increasing and decreasing 500-ms injected square-wave depolarizing current pulses was used to describe rhythmic motoneuron properties. The steepest slope occurred in the S group (55.3 ± 22.2 Hz/nA), followed by the T group (35.5 ± 15.3 Hz/nA), while the flattest slope was found in the E group (25.4 ± 10.9 Hz/nA). The steepest steady-state slope occurred in the S group but was found to be similar between the T and E groups. Furthermore, a spike-frequency adaptation (SFA) index revealed a slower adaptation in motoneurons of the E animals only (∼40% lower). Finally, evidence for a secondary range of firing existed more frequently in the T group (41%) compared with the S (12%) and E (31%) groups. The lower F/I slope and lower SFA index of motoneurons for E rats may be a result of an increase in Na+ conductance at the initial segment. The results show that motoneuronal rhythmic firing behavior is plastic, depending on the volume of daily activation and on intact descending pathways.

The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40 months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4 months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

Neuronal and vascular reorganization after spinal cord injury (SCI) is scarcely known although its characterization has major implications in understanding the functioning of the altered spinal cord. Several electrophysiological and anatomical lines of evidence support plasticity caudal to the lesion site, but do not provide sufficient clues about neuronal and vascular reorganization after SCI. The aim of the present study was to compare neuronal activation in the lumbar spinal cord between uninjured and SCI rats with novel optical imaging technology. The results showed significant haemodynamic response differences after sciatic nerve stimulation in uninjured controls, in comparison to SCI rats. Both timing and shape of the response were modified. In uninjured rats, blood flow presented an initial dip but was rapidly drained from the activation site through the venous system. In comparison, the blood transfer rate in SCI rats was much slower. Damaged blood vessels at the lesion site after thoracic SCI impacted the vascular response upon neuronal activation in the lumbar spinal cord. This observation is important in the study of spinal cord function after SCI by imaging techniques based on haemodynamics (blood oxygenation level-dependent using functional magnetic resonance imaging (BOLD fMRI) and optical imaging). In conclusion, our results indicate that new avenues quantifying the influence of vascular plumbing will have to be developed to explore the efficacy of rehabilitation and pharmacological therapies by haemodynamic imaging.

The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5mg/kg) at 2h after the contusion injury; (2) physiological saline at 2h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p

Rolipram, an inhibitor of phosphodiesterase 4 (PDE4) proteins that hydrolyze cAMP, increases axonal regeneration following spinal cord injury (SCI). Recent evidence indicates that rolipram also protects against a multitude of apoptotic signals, many of which are implicated in secondary cell death post-SCI. In the present study, we used immunohistochemistry and morphometry to determine potential spinal cord targets of rolipram and to test its protective potential in rats undergoing a cervical spinal cord contusive injury. We found that 3 PDE4 subtypes (PDE4A, B, D) were expressed by spinal cord oligodendrocytes. OX-42 immunopositive microglia only expressed the PDE4B subtype. Oligodendrocyte somata were quantified within the cervical ventrolateral funiculus, a white matter region critical for locomotion, at varying time points after SCI in rats receiving rolipram or vehicle treatments. We show that rolipram significantly attenuated oligodendrocyte death at 24 hours post-SCI continuing through 72 hours, the longest time point examined. These results demonstrate for the first time that spinal cord glial cells express PDE4 subtypes and that the PDE4 inhibitor rolipram protects oligodendrocytes from secondary cell death following a contusive SCI. They also indicate that further investigations into neuroprotection and axonal regeneration with rolipram are warranted for treating SCI.

The aim of the present study was to characterize a novel electrophysiological assessment, the magnetically evoked interenlargement response (MIER), by defining the anatomical location of the fast conducting (large myelinated) ascending axons that mediate the response and the relationship between the response and locomotor function following experimental spinal cord injury. Electromyographic (EMG) responses were recorded from the triceps muscles following magnetic stimulation of one hip. Short-latency (approximately 6 ms) EMGs were recorded from triceps muscles in normal controls and following different laceration injuries (dorsal, lateral or dorsal and lateral hemisections) or a 150-kilodyne (kd) contusion injury at the T9 level. The amplitude of the triceps MIER was significantly correlated to the area of spared white matter in the lateral funiculus and to hindlimb function during open field locomotion (r2 = 0.55). Following a complete lateral hemisection, MIERs were present in the triceps bilaterally following stimulation of either hip. Responses could also be recorded from the masseter muscles indicating that the influence of this pathway extends beyond the spinal cord. Anatomical evidence of a bilaterally distributed propriospinal pathway was found when biotinylated dextran amine (BDA) was injected into the lateral white matter on one side of the spinal cord at T9. BDA-labeled axons with varicosities were found bilaterally in the intermediate and ventral gray matter of the caudal region of the cervical enlargement. These observations suggest that MIERs may be useful to quantitatively assess neurotransmission and functional recovery over time after experimental spinal cord injury.

In spite of our knowledge of activity related adaptations in supraspinal neurones and skeletal muscles, very little is known concerning adaptations in α-motoneurones to alterations in chronic activity levels. Recent evidence shows that the biophysical properties of α-motoneurones are plastic and adapt to both increases and decreases in chronic activation. The nature of the adaptations-in resting membrane potential, spike threshold, afterhyperpolarization amplitude, and rate of depolarization during spike generation-point to involvement of density, type, location, and/or metabolic modulation of ion conductance channels in the motoneuronal membrane. These changes will have significant effects on how motoneurones respond when activated during the generation of movements, and on the effort required to sustain activation during prolonged exercise. Since the adaptations most likely involve structural changes in the motoneurones and changes in protein synthesis, and change the output response of the cells to input, they are considered to be learning responses. Future research directions for examining this issue are outlined. Key words: α-motoneurones, exercise, training, spinal cord, learning, disuse, spinal cord transection

Neuronal, vascular and metabolic factors result in a deterioration of the cerebral hemodynamic response with age. The interpretation of neuroimaging studies in the context of aging is rendered difficult due to the challenge in untangling the composite effect of these modifications. In this work we integrate multimodal optical imaging in biophysical models to investigate vascular and metabolic changes occurring in aging. Multispectral intrinsic optical imaging of an animal model of healthy aging, the LOU/c rat, is used in combination with somatosensory stimulation to study the modifications of the hemodynamic response with increasing age. Results are fitted with three macroscopic biophysical models to extract parameters, providing a phenomenological description of vascular and metabolic changes. Our results show that 1) biophysical parameters are estimable from multimodal data and 2) parameter estimates in this population change with aging.

Intrinsic optical imaging (IOI) has emerged as a very powerful tool to assess neuronal function in small animals. Although it has been used extensively in the brain, its application to the spinal cord is rare. The inability of intrinsic optical techniques to resolve different depths and embedded gray matter hampers their capacity to distinguish larger vasculature contributions of hemodynamic signals originating from motoneuron and interneuron activation. Laminar optical tomography (LOT) is a recently-developed method that fills the gap left between IOI and diffuse optical imaging. With distinct source-detector separations, light that propagates deeper into tissues can be distinguished from light originating from the surface, providing depth sensitivity. In this work, LOT is investigated for the first time to image spinal cord activation with simultaneous IOI of the cortex in rats. Such proof of concept provides a powerful imaging modality to study spinal cord activation and disruption after injury.

Quantifying spinal cord functions is crucial for understanding neurophysiological mechanisms governing the intact and the injured spinal cord. Intrinsic optical imaging (IOI) and laser speckle provides measures of deoxyhemoglobin (HbR) and oxyhemoglobin (HbO 2 ) concentrations, blood volume (BV) and blood flow (BF) at high spatial and temporal resolution. In this study we used IOI and laser speckle to characterize the hemodynamic response to neuronal activation in the lumbar spinal cord of anaesthetized rats ( N = 9). We report consistent temporal variations of HbR, HbO 2 , BV and BF located ipsilaterally at L3–L5. Responses were significantly higher when stimulation intensity was increased. Vascular changes extended several millimetres from the epicenter, supporting the venous drainage observed in functional magnetic resonance imaging studies.

opital du Sacr´ e-Coeur de Montr´ eal, Dde chirurgie, Universit ´ e de Montr´ eal, MontrQC, Canada Abstract. Purpose: nerve regeneration and functional recovery are often incomplete after peripheral nerve damage. The aim of this study was to determine if chondroitinase ABC injection at the lesion site, 1 hour of electrical stimulation and the combination of these treatments at the time of repair could be effective in promoting muscle reinnervation. Methods: the right sciatic nerve was completely sectioned in 32 female Sprague-Dawley rats. End-to-end microsuture repair was undertaken and fibrin glue was added. Five groups were studied: 1) suture (S) + fibrin glue (F) only; 2) S + F + chondroitinase ABC; 3) S + F + electrical stimulation; 4) S + F + chondroitinase ABC + electrical stimulation; 5) uninjured nerve. Results: post recovery kinematics showed larger excursion of the hip-ankle-toe angle during walking in groups 2, 3 and 4 than in group 1 ( p< 0.05). In vivo electromyographic activity and maximal muscle force were similar between groups 2, 3, 4 and 5, with higher values in all of them compared to group 1 ( p< 0.05). Also, the distal stump of the sciatic nerve was excised, and cross-sectioning revealed that the number of axons were similar in all groups. Conclusions: 150 days after nerve transection, recovery was incomplete with S and F only. Chondroitinase ABC injection at the lesion site and/or 1 hour of electrical stimulation of the proximal nerve stump were beneficial in promoting nerve regeneration and functional muscle reinnervation.

Traumatic human spinal cord injury causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after SCI are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus express 3′-5′-cyclic adenosine monophosphate-dependent phosphodiesterase 4 subtypes and that their death was attenuated up to 3 days after contusive cervical spinal cord injury when rolipram, a specific inhibitor of phosphodiesterase 4, was administered. Here, we report that 1) there are more oligodendrocyte somata in the adult rat epicenter ventrolateral funiculus, 2) descending and ascending axonal conductivity in the ventrolateral funiculus improves, and that 3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical spinal cord injury when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a spinal cord injury with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with spinal cord injury.

The aim of the present study was to evaluate the effect of a stepping-based rehabilitation program in voluntary wheel cages on the functional recovery and electrophysiological properties of neurons in the rat lumbar spinal cord after compressive thoracic (T10) spinal cord injury (SCI). A significant decrease in stance/swing duration and the number of limbs simultaneously in the stance phase was seen in trained compared to sedentary rats at 28 days after SCI (p

We sought to determine whether decreased neuromuscular use in the form of hindlimb unweighting (HU) would affect the properties of innervating motoneurones. Hindlimb weight-bearing was removed in rats for a period of 2 weeks via hindlimb suspension by the tail. Following this the electrophysiological properties of tibial motoneurones were recorded under anaesthesia in situ. After HU, motoneurones had significantly (P < 0.05) elevated rheobase currents, lower antidromic spike amplitudes, lower afterhyperpolarization (AHP) amplitudes, faster membrane time constants, lower cell capacitances, and depolarized spike thresholds. Frequency–current (f–I) relationships were shifted significantly to the right (i.e. more current required to obtain a given firing frequency), although there was no change in f–I slopes. ‘Slow’ motoneurones (AHP half-decay times, > 20 ms) were unchanged in proportions in HU compared to weight-bearing rats. Slow motoneurones had significantly lower minimum firing frequencies and minimum currents necessary for rhythmic firing than ‘fast’ motoneurones in weight-bearing rats; these differences were lost in HU rats, where slow motoneurones resembled fast motoneurones in these properties. In a five-compartment motoneurone model with ion conductances incorporated to resemble firing behaviour in vivo, most of the changes in passive and rhythmic firing properties could be reproduced by reducing sodium conductance by 25% and 15% in the initial segment and soma, respectively, or by increasing potassium conductance by 55% and 42%, respectively. This supports previous conclusions that changes in chronic neuromuscular activity, either an increase or decrease, may result in physiological adaptations in motoneurones due to chronic changes in ion conductances.

Spinal cord transection influences the properties of motoneurons and muscles below the lesion, but the effects of interventions that conserve muscle mass of the paralyzed limbs on these motoneuronal changes are unknown. We examined the electrophysiological properties of rat lumbar motoneurons following spinal cord transection, and the effects of two interventions shown previously to significantly attenuate the associated hindlimb muscle atrophy. Adult rats receiving a complete thoracic spinal cord transection (T-10) were divided into three groups receiving: (1) no further treatment; (2) passive cycling exercise for 5 days/week; or (3) acute transplantation of fetal spinal cord tissue. Intracellular recording of motoneurons was carried out 4-5 weeks following transection. Transection led to a significant change in the rhythmic firing patterns of motoneurons in response to injected currents, as well as a decrease in the resting membrane potential and spike trigger level. Transplants of fetal tissue and cycling exercise each attenuated these changes, the latter having a stronger effect on maintenance of motoneuron properties, coinciding with the reported maintenance of structural and biochemical features of hindlimb muscles. The mechanisms by which these distinct treatments affect motoneuron properties remain to be uncovered, but these changes in motoneuron excitability are consistent with influences on ion conductances at or near the initial segment. The results may support a therapeutic role for passive limb manipulation and transplant of stem cells in slowing the deleterious responses of motoneurons to spinal cord injury, such that they remain more viable for subsequent alternative strategies.

The purpose of the study was to determine the effect of daily endurance treadmill training (2 h/day, 30 m/min) on motoneuron biophysical properties. Electrophysiological properties of tibial motoneurons were measured in situ in anesthetized (ketamine/xylazine) control and trained rats using sharp glass microelectrodes. Motoneurons from trained rats had significantly hyperpolarized resting membrane potentials and spike trigger levels, and faster antidromic spike rise-times. “Fast” motoneurons (after-hyperpolarization half-decay time

No evidence currently exists that motoneurone adaptations in electrophysiological properties can result from changes in the chronic level of neuromuscular activity. We examined, in anaesthetized (ketamine/xylazine) rats, the properties of motoneurones with axons in the tibial nerve, from rats performing daily spontaneous running exercise for 12 weeks in exercise wheels (‘runners’) and from rats confined to plastic cages (‘controls’). Motoneurones innervating the hindlimb via the tibial nerve were impaled with sharp glass microelectrodes, and the properties of resting membrane potential, spike threshold, rheobase, input resistance, and the amplitude and time-course of the afterhyperpolarization (AHP) were measured. AHP half-decay time was used to separate motoneurones into ‘fast’ (AHP half-decay time < 20 ms) and ‘slow’ (AHP half-decay time ≥ 20 ms), the proportions of which were not significantly different between controls (58 % fast) and runners (65 % fast). Two-way ANOVA and ANCOVA revealed differences between motoneurones of runners and controls which were confined to the ‘slow’ motoneurones. Specifically, runners had slow motoneurones with more negative resting membrane potentials and spike thresholds, larger rheobasic spike amplitudes, and larger amplitude AHPs compared to slow motoneurones of controls. These adaptations were not evident in comparing fast motoneurones from runners and controls. This is the first demonstration that physiological modifications in neuromuscular activity can influence basic motoneurone biophysical properties. The results suggest that adaptations occur in the density, localization, and/or modulation of ionic membrane channels that control these properties. These changes might help offset the depolarization of spike threshold that occurs during rhythmic firing.