Efficiency of Sensorimotor Networks: Posture and Gait in Young and Older Adults.

Background/Study context: Posture and gait are complex sensorimotor functions affected by age. These difficulties are particularly apparent when performing cognitively demanding tasks. Characterizing the functional organization of brain networks involved in these associations remains a challenge because of the incompatibility of brain imagery techniques with gross body movements. The present study aimed at testing whether resting-state functional connectivity of sensorimotor networks is associated with posture and gait performance recorded offline, in young and older adults. METHODS: Young (n = 12, mean = 24.1 y/o) and older (n = 14, mean = 65.6 y/o) healthy adults were tested for stability of their posture and gait. Four hours later, anatomical and functional brain imaging data were collected with Magnetic Resonance Imaging (MRI). Bilateral precentral and postcentral gyri were used as seeds in a graph theory analysis focused on global and local efficiency. The possible association between these data and posture and gait performance was examined. RESULTS: Both samples presented similar sensorimotor graphs, but with different global and local efficiencies (small world properties). The association between the networks' graph measures and posture and gait performance also differed across groups: local efficiency was correlated with gait stability in challenging conditions in older adults, but not in young adults. CONCLUSION: This exploratory study suggests that combining analyses of functional networks and offline body movement may provide important information about motor function. In older adults, the association between graph properties of the sensorimotor network and gait performance in challenging conditions may be indicative of compensatory processes. Prospective studies involving more subjects with a larger age range are warranted.

The restless legs syndrome.

The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.

Regulation by glycine, Mg2+ and polyamines of the N-methyl-D-aspartate-induced locomotion in the neonatal rat spinal cord in vitro.

Excitatory amino acids are known to activate the spinal neural network that organize locomotor activity in various species. In this study, the role of various compounds which alter the functioning of the N-methyl-D-aspartate receptor (glycine, Mg2+ ions and spermine) was investigated during fictive locomotion, using an in vitro isolated spinal cord preparation from neonatal rats. Locomotor-like activity induced by excitatory amino acids was recorded both extra- and intracellularly. 7-chloro-kynurenic acid, an antagonist of the glycine site at the N-methyl-D-aspartate receptor, depressed the N-methyl-D-aspartate component of the synaptic inputs received by the motoneurons. Glycine at low concentrations had no effect on locomotor activity, while 7-chlorokynurenic acid increased the locomotor period and decreased the burst amplitude in a dose-dependent manner. Removal of Mg2+ ions from the saline facilitated the N-methyl-D-aspartate-mediated response, and triggered spontaneous bursting activity, abolished by 2-amino-5-phosphonovaleric acid, an antagonist of the N-methyl-D-aspartate receptor. The polyamine, spermine, did not change the locomotor parameters. On the contrary, arcaine, a putative antagonist of the polyamine site on the N-methyl-D-aspartate receptor, increased locomotor activity. The effects of arcaine were counteracted by spermine. These results suggest that glycine and spermine are present at saturating concentrations on the N-methyl-D-aspartate receptor during ongoing locomotion. Together with Mg2+ ions, these endogenous regulators contribute to control the level of activity of the N-methyl-D-aspartate receptor in the spinal cord of the neonatal rat.

GABAergic control of spinal locomotor networks in the neonatal rat.

We studied the GABAergic control of the spinal locomotor network using an isolated brain stem/spinal cord from newborn rats, in which locomotor-like activity was recorded. We demonstrate that endogenously released GABA controls the locomotor network, by decreasing or completely abolishing all locomotor-like activity. At first, we investigated the role played by GABA in the control of the locomotor period. By separately superfusing various compartments of the lumbar cord, we identified the targets of GABA. When bath-applied on the upper lumbar segments (L1/L2), GABA or its agonists (muscimol, baclofen) modulated the locomotor period, whereas it had no effects when bath-applied on the caudal lumbar cord (L3/L6). In the second step we studied how GABA may presynaptically control the locomotor drive arising from the locomotor network located in L1/L2. By use of the partitioned spinal cord, intracellular recordings from the caudal pool motoneurons (L4/L5) were performed, while initiating locomotor-like activity in L1/L2. We found that GABA or its agonists decreased the monosynaptic locomotor drive that the motoneurons received from the L1/L2 network, and we found a presynaptic effect exerted through the activation of GABAB receptors. In conclusion, this study emphasizes the role played by GABA at various levels in the control of the locomotor network in mammals.

A cooling/heating system for use with in vitro preparations: study of temperature effects on newborn rat rhythmic activities.

We have developed a universal stage that is particularly suitable for use with vertebrate and invertebrate in vitro preparations. Based on the Peltier effect, the same compact apparatus can be used to cool or heat within a wide temperature range (from 5 to 50 degrees C). Due to the use of interchangeable rings, the stage is compatible with a wide variety of dishes. We used this system to analyze the effects of temperature on the spinal networks that generate fictive locomotion in newborn rats. The results showed that these spinal networks can be active in a wide temperature range, producing an organized pattern (bursts alternating between the right and left sides) even at very low temperatures (15 degrees C). From 15 to 20 degrees C the period decreased before reaching a plateau (between 20 to 30 degrees C).

Variability as a characteristic of immature motor systems: an electromyographic study of swimming in the newborn rat.

Swimming behaviour was studied in neonate rats by carrying out electromyographic recordings. The study showed that the early swimming pattern was characterized by highly instable temporal parameters. A decrease was found to occur with age in the variability of the instantaneous period in each leg and in that of the antiphase pattern. Moreover, a dissociation occurred during development between the foreleg and the backleg activity. While patterns involving the forelegs always remained extremely instable, a considerable improvement was found to occur with time in the hindlimb activity.

Noradrenergic control of locomotor networks in the in vitro spinal cord of the neonatal rat.

In this paper, we address the role of noradrenaline (NA) in the control of locomotor networks in the neonatal rat. Using an in vitro isolated spinal cord preparation, we observed that bath application of NA elicited an extremely slow alternating motor pattern (period around 80-90 s) alternating between contralateral sides, which was recorded in the lumbar ventral roots but not between flexor and extensor units. These effects of NA were mimicked by the alpha1 agonists methoxamine and phenylephrine, whereas alpha2 and beta receptors bath-applied alone did not elicit any activity. NA slightly affected the locomotor-like activity induced by the activation of NMDA receptors, whereas the alpha1 agonists speeded up the locomotor activity. Both the activation of alpha2 and beta agonist receptors slowed down the motor rhythm while simultaneously increasing the burst amplitude in the case of the beta agonists. NA depolarized the motoneurones and increased their input membrane resistance. It was concluded that NA does not trigger locomotor activity, but modulates the activity of the locomotor networks. This multimodal control is mediated by the activation of a variety of receptor types.

Differential effects of potassium channel blockers on the activity of the locomotor network in neonatal rat.

The role played by various K+ channels during locomotor activity was studied using an in vitro neonatal rat spinal cord preparation. Locomotor-like activity was elicited by bath-applying serotonin (5-HT) and N-methyl-d-l-aspartate (NMA). Four different K+ channel blockers were tested by adding them to the superfusing saline. Each of the K+ channel blockers elicited a characteristic motor pattern with specific temporal parameters. Cs+ and tetraethyl ammonium both decreased the motor period, but had opposite effects on the burst amplitude. Apamin increased both the motor period and the burst amplitude. A dose-response relationship was established for the K+ channel blockers. The blockers elicited an unstable rhythmic activity, contrary to what occurred under control conditions. We also found that due to the specific changes that they elicit, the various blockers produce selective changes in the burst ratio. These results suggest that the various K+ channels contribute differently to the generation of locomotor activity.

Suppressive control of a rhythmic central pattern generator by an identified modulatory neuron in crustacea.

The activity of the 14 neuron network which organizes the pyloric motor rhythm in the stomatogastric ganglion of the lobster, Homarus gammarus, is controlled by neuromodulatory inputs which have been described as having mainly 'permissive' effects. By contrast, here we identify a neuron, the pyloric suppressor (PS) neuron which exerts a 'suppressive' effect on the pyloric activity. We show that PS neuron discharge can terminate in a long-lasting manner, spontaneous pyloric rhythmic activity. Its effect results from a direct suppression of the endogenous ability of the pyloric pacemaker neurons to produce rhythmic bursts of action potentials. Thus the output of the pyloric neuronal network appears to be finely tuned by neuromodulatory influences having opposite effects.

N- and P/Q-type Ca(2+) channels are involved in neurotransmitter release but not in synaptic depression in the spinal cord of the neonatal rat.

This study investigated the involvement of N- and P/Q-type Ca(2+) channels in sensorimotor transmission and synaptic depression in the in vitro neonatal rat spinal cord preparation. Postsynaptic potentials were intracellularly recorded from spinal motoneurones during stimulation of the dorsal roots. We found that omega-agatoxin-IVA (P/Q-type Ca(2+) channels blocker), omega-conotoxin-GVIA (N-type Ca(2+) channel blocker) and omega-conotoxin-MVIIC (N-, P/Q-type Ca(2+) channel blocker) markedly decreased both poly- and monosynaptic potentials. We also found that the frequency-dependent depression which occurred in the monosynaptic response, for stimulus intervals shorter than 30 s, persisted in the presence of the various Ca(2+) channels blockers. Hyperpolarizing the motoneurons significantly reduced depression, suggesting contribution from some additional postsynaptic mechanisms. We conclude that at birth, as in adult central nervous system (CNS) synapses, several types of voltage dependent calcium channels mediate sensorimotor neurotransmission and that synaptic depression, which is characteristic of neonatal sensorimotor transmission, does not involve these Ca(2+) channels.

Two types of motor rhythm induced by NMDA and amines in an in vitro spinal cord preparation of neonatal rat.

Rhythmic motor activities were studied in two rat spinal cord preparations; in the first one, the spinal cord was completely isolated and the ventral roots activity was recorded; in the other, spinal cord and hindlimbs were kept in order to record muscle activities. Motor patterns were therefore recorded in ventral roots and/or hindlimb muscles. Two kinds of specific patterns were elicited by neurochemicals. The first which was induced by N-methyl-D,L-aspartate (NMDA) and serotonin (5-HT) was a slow rhythm (0.5-0.2 Hz) of left and right alternating bursts of spikes. The second one which was induced by NMDA, 5-HT and norepinephrine (NE), was a high frequency rhythm (5-10 Hz). One particularity observed was that these two rhythms could occur simultaneously. The relationship between the two in vitro rhythms is discussed and they are compared with those reported in other rhythmic systems.

Ubiquity of motor networks in the spinal cord of vertebrates.

In a recent paper, we found that it is possible to record motor activity in sacral segments in the in vitro neonatal rat spinal cord preparation. This motor activity recorded in segments that are not innervating hindlimbs is driven by the lumbar locomotor network. Indeed, compartimentalizations of the cord with Vaseline walls or section experiments, reveals that the sacral segments possess their own rhythmogenic capabilities but that in an intact spinal cord they are driven by the lumbar locomotor network. In this review, these recent findings are placed in the context of spinal motor network interactions. As previously suspected, the motor networks do not operate in isolation but interact with each other according to behavioural needs. These interactions provide some insight into the discrepancies observed in several studies dealing with the localization of the lumbar locomotor network in the neonatal rat spinal cord. In conclusion, the spinal cord of quadrupeds appears as an heterogeneous structure where it is possible to identify neuronal networks that are crucial for the genesis of locomotor-related activities.

Coupling between lumbar and sacral motor networks in the neonatal rat spinal cord.

We have studied the rhythm-generating capabilities of the lumbar, sacral and coccygeal (Co) areas using an isolated spinal cord preparation of the newborn rat. The bath-application of a mixture of N-methyl-D-L-aspartate (NMA) and serotonin (5-HT) on the whole spinal cord induced a coordinated rhythmic activity that could be recorded from the lumbar to the coccygeal ventral roots. The phase relationships and mean burst duration between the activity in the rostral lumbar segments and the activity in the sacral segments was analysed. The direct activation of the sacral network, by using sections or by selective pharmacological activation, showed that these caudal segments possess their own rhythmogenic capability. By combining section experiments and compartmentation of the spinal cord, we demonstrated that a strong coupling exists between the lumbar and sacral motor networks. In addition, we found that in an intact spinal cord the activity of the sacral networks is driven by the lumbar networks. We have found that different modes of coordination between the lumbar and the sacral activity may occur. Finally, we have shown that the coupling between the lumbar and sacral networks can be modified by sensory inputs, suggesting that the spinal machinery could modulate and adapt the coupling of these two spinal networks.

Presynaptic GABAergic control of the locomotor drive in the isolated spinal cord of neonatal rats.

The in vitro newborn rat isolated brain stem/spinal cord preparation was used to study the involvement of presynaptic inhibition in the control of the synaptic locomotor drive. The recording chamber was partitioned with Vaseline walls to separate the L1-L2 locomotor network from the motoneurons in the lower segments. When locomotor like activity was induced by bath applying a mixture of N-methyl-D-L-aspartate and serotonin to the L1-L2 segments, intracellular recordings of L3-L5 motoneurons show an alternating pattern of monosynaptic excitatory glutamatergic and inhibitory glycinergic inputs known as the locomotor drive. Gamma-aminobutyric acid (GABA), baclofen and muscimol (respectively GABA(B) and GABA(A) agonists) superfused on the L3-L5 segments depressed the synaptic locomotor drive of motoneurons during the ongoing activity. On the contrary, the GABA(B) receptor antagonist CGP35348 enhanced the locomotor drive, which suggests that an endogenous release of GABA occurs during locomotor-like activity. Baclofen, unlike muscimol and GABA, did not affect the passive membrane properties and the firing discharge of synaptically isolated motoneurons. Baclofen and muscimol acted on the two phases (inhibitory and excitatory) of the synaptic drive. The effects of GABAergic agonists on the whole locomotor activity were tested. When superfused on the L3-L5 part of the cord, they affected only the L5 burst amplitude. When bath-applied to the L1-L2 network, GABA and muscimol decreased the amplitude of the L2 and L5 bursts and increased the locomotor period while baclofen had significant effects only on the period. It was concluded that GABA modulates the information conveyed by the L1-L2 network to its target motoneurons presynaptically via GABA(B) and possibly GABA(A) receptors and postsynaptically, via GABA(A) receptors.

Postinhibitory rebound during locomotor-like activity in neonatal rat motoneurons in vitro.

The aim of this study was to establish how a membrane property contributes to the neuronal discharge during ongoing behavior. We therefore studied the role of the postinhibitory rebound (PIR) in the bursting discharge of lumbar motoneurons intracellularly recorded in newborn rat in vitro brain stem/spinal cord preparation. The PIR is a transient depolarization that occurs after a hyperpolarization. We first investigated how it was expressed during experimentally induced hyperpolarizations. Its amplitude increased with the inhibition and was voltage dependent. The Ca2+ channel blockers Mn2+ and Co2+ partly suppressed the PIR in a few of the motoneurons tested. When hyperpolarized, the motoneurons exhibited a sag that was associated with the PIR. Adding caesium to the bath abolished both sag and rebound, which suggested that the PIR in the lumbar motoneurons was mainly due to the activation of the inward rectifying current IQ. In the second part, we studied the physiological involvement of PIR during fictive locomotion induced by bath application of N-methyl-D-L-aspartate and serotonin. We established that experimentally induced PIR could initiate or modulate the bursting discharge of motoneurons during fictive locomotion. We then studied whether the firing patterns of the motoneurons were correlated in one way with the synaptic inhibition. When the monosynaptic inhibitory input to the motoneurons was abolished with the glycinergic blocker strychnine, these neurons stopped discharging (although they still were depolarized rhythmically). The firing of action potentials was restored by applying negative current pulses. This study provides evidence as to how one membrane property in mammals is involved in a complex type of behavior, namely locomotion.

Evidence for the existence of a functional polysynaptic pathway from trigeminal afferents to lumbar motoneurons in the neonatal rat.

Stimulation of trigeminal afferents has been reported to have powerful effects on the spinal cord in adult animals of several species. In the present study, the pathway transmitting these influences was investigated in the neonatal rat. Experiments were performed on in vitro brainstem/spinal cord preparations. Stimulation of the trigeminal nerve evoked bilateral polysynaptic discharges in lumbar ventral roots. Intracellular recordings from lumbar motoneurons showed mainly excitatory responses, although a few inhibitory responses were also observed. Experiments with perfusion of different parts of the preparation with general or selective synaptic blockers revealed a synaptic relay under GABAergic control in the brainstem, and at least one synapse in the cervical and in the thoracic spinal cord. The involvement of lumbar interneurons was established by perfusing the lumbar enlargement with saline containing either a high concentration of divalent ions or mephenesin in order to reduce transmission along polysynaptic pathways. The contribution of excitatory amino acid transmission was evaluated and was found to evoke mixed receptor responses. The course of the pathway was traced by using different lesions to the brainstem and spinal cord. The pathway was found to be ipsilateral in the brainstem and to become bilateral in the spinal cord. The results of the present study demonstrate that polysynaptic sensorimotor pathways are present at birth. The results are discussed in relation to the pontomedullary locomotor strip, which has been thought to share many features with the trigeminal system.

GABAergic inactivation of the central pattern generators for locomotion in isolated neonatal rat spinal cord.

1. Experiments were performed using an isolated brainstem-spinal cord preparation from newborn rats, in order to study the GABAergic control of the spinal neuronal networks that generate locomotor rhythms in mammals. Locomotor-like activities were recorded in the ventral roots, and the various neurochemical compounds were added to the superfusion saline. 2. Bath application of GABA suppressed in a dose-dependent manner the motor activity induced by an excitatory amino acid N-methyl-D,L-aspartate (NMA). Both the GABAA agonist muscimol and the GABAB agonist baclofen mimicked the effects of GABA, since they either slowed down or stopped the rhythmic activity. 3. Experiments were performed in which the lumbar compartment was superfused separately from the brainstem. Chemical activation of the brainstem by NMA alone failed to induce locomotor-like activity. When GABAA (bicuculline) and GABAB (phaclofen) antagonists were simultaneously bath applied to the lumbar spinal cord, however, locomotor-like activity was induced. 4. The GABA uptake inhibitors nipecotic acid and guvacine suppressed the rhythmic motor pattern induced by NMA in a dose-dependent manner. The effects of nipecotic acid were reversed by bicuculline and phaclofen. 5. Bicuculline added during NMA-induced locomotor-like activity greatly increased both the frequency and amplitude of motor bursts, while phaclofen modified only the frequency. 6. The motor pattern depended on the balance between activatory and inactivatory influences, since the rhythmic patterns recorded with low doses of NMA associated with high doses of bicuculline were similar to those elicited by higher doses of NMA associated with low doses of bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-linear development of the frequency of swimming movements during ontogeny in rats]. / Evolution non linéaire de la fréquence des mouvements de nage pendant l'ontogenèse chez le rat.

The choice of swimming as locomotor behaviour was justified by the fact that it could be elicited from birth to adult age. We have recorded electromyographic activities during swimming movements, on flexor muscles in front legs and hind legs (Spinodeltoidus and Gluteus superficialis). The mean frequency of activity of each limb during swimming, for animals aged from 0 to 20 or 30 days was then computed. The results showed an increase in frequency between 0 and 20 days from 1 to 4 Hz. This increase was not linear, but composed of different successive phases. After a first period of increase between 0 and 6 days (slope 0.25), for the hind limbs and the fore-limbs, we noted a plateau between 6 and 12 days during which the frequency was stable. This plateau was followed by another increase in the frequency values between 12 and 16 days (slope 0.30), followed by another plateau that corresponded to the adult frequency.

Suppression of oscillatory activity in crustacean pyloric neurons: implication of GABAergic inputs.

Generation of rhythmic pyloric motor output in the crustacean stomatogastric ganglion results from synaptic connections and cellular properties of a 14-cell network of pyloric neurons. These cellular properties are under the influences of modulatory inputs, which act, for the most part, in an activating mode, i.e., they enhance the bursting properties of the pyloric neurons and/or their ability to express their regenerative properties. Here we attempt to demonstrate that the pyloric motor output is also under the control of suppressive afferent inputs that are able to stop the pyloric rhythm in a long-lasting manner. Immunohistochemistry, using GABA antibodies, indicates that GABAergic-like fibers are present in both the stomatogastric ganglion and its afferent nerve. Bath-applied GABA suppresses spontaneous pyloric rhythmic activity. This is due to an inability of the pyloric pacemakers to express their bursting properties. The suppressive effect of GABA is blocked by picrotoxin and mimicked by muscimol. Isolating the pyloric neurons from all descending spiking influences with tetrodotoxin demonstrates that exogenously applied GABA acts directly on the pyloric neurons. To confirm the existence of a physiological suppressive system for the pyloric motor pattern, we show that the stimulation of an afferent nerve, known to contain GABA-like fibers, also causes the cessation of rhythmic activity and the inability of the pyloric neurons to express their bursting properties.