Direct glutamate-mediated presynaptic inhibition of sensory afferents by the postsynaptic motor neurons

International audienceAn in vitro preparation of the crayfish central nervous system was used to study a negative feedback control exerted by the glutamatergic motor neurons (MNs) on to their presynaptic cholinergic sensory afferents. This negative control consists in small amplitude, slowly developing depolarizations of the primary afferents (sdPADs) strictly timed with MN bursts. They were not blocked by picrotoxin, but were sensitive to glutamate non-N-methyl-D-aspartate (NMDA) antagonists. Intracellular recordings were performed within thin branches of sensory terminals while electrical antidromic stimulation were applied to the motor nerves, or while glutamate (the MN neurotransmitter) was pressure-applied close to the recording site. Electrical motor nerve stimulations and glutamate pressure application had similar effects on to sensory terminals issued from the coxo-basipodite chordotonal organ (CBTs): like sdPADs, both stimulation-induced depolarizations were picrotoxin-resistant and were dramatically reduced by non-NMDA antagonist bath application. These results indicate that sdPADs are likely directly produced by MNs during locomotor activity. A functional scheme is proposed

Adaptive motor control in crayfish

International audienceThis article reviews the principles that rule the organization of motor commands that have been described over the past ®ve decades in cray®sh. The adaptation of motor behaviors requires the integration of sensory cues into the motor command. The respective roles of central neural networks and sensory feedback are presented in the order of increasing complexity. The simplest circuits described are those involved in the control of a single joint during posture (negative feedback±resistance re¯ex) and movement (modulation of sensory feedback and reversal of the re¯ex into an assistance re¯ex). More complex integration is required to solve problems of coordination of joint movements in a pluri-segmental appendage, and coordination of dierent limbs and dierent motor systems. In addition, beyond the question of mechanical ®tting, the motor command must be appropriate to the behavioral context. Therefore, sensory information is used also to select adequate motor programs. A last aspect of adaptability concerns the possibility of neural networks to change their properties either temporarily (such on-line modulation exerted, for example, by presynaptic mechanisms) or more permanently (such as plastic changes that modify the synaptic ecacy). Finally, the question of how``automatic'' local component networks are controlled by descending pathways, in order to achieve behaviors, is discussed.

Neural Mechanisms of Reflex Reversal in Coxo-Basipodite Depressor Motor Neurons of the Crayfish

International audienceNeural mechanisms of reflex reversal in coxo-basipodite depressor motor neurons of the crayfish. J. Neurophysiol. 77: 1963–1978, 1997. The in vitro preparation of the fifth thoracic ganglion of the crayfish was used to investigate the mechanisms underlying the reflex reversal in a sensory-motor pathway. Sensory afferent neurons from the coxo-basipodite chordotonal organ (CBCO), which senses vertical movements of the limb, connect monosynaptically with basal limb motor neurons (MNs). In tonically active preparation, stretching the CBCO (corresponding to downward movements of the leg) stimulates the levator MNs, whereas releasing the CBCO activates the depressor (Dep) MNs. These reflexes, opposed to the imposed movement, are termed resistance reflexes. By contrast, during fictive locomotion, the reflexes are reversed and termed assistance reflexes. Intracellular recordings from all 12 Dep MNs were performed in single experiments. It allowed us to characterize three types of Dep MNs according to their response to CBCO imposed step-and-ramp movements: 8 of the 12 Dep MNs are resistance MNs that are depolarized during release of the CBCO and are connected monosynaptically to release-sensitive CBCO neurons; 1 Dep MN is an assistance MN that is depolarized during stretching of the CBCO and is connected monosynaptically to exclusively velocity-coding stretch-sensitive CBCO neurons; in our experimental conditions, 3 Dep MNs do not display any response to CBCO stimulation. Assistance reflex interneurons (ARINs), involved in polysynaptic assistance reflexes recorded from depressor MNs, are presented. During low-velocity (0.05 mm/s) stretching ramps imposed on the CBCO, ARINs display compound excitatory postsynaptic potentials (EPSPs), whereas during high-velocity (0.25 mm/s) ramps, they display a mixed excitatory and inhibitory response. Whereas a single MN generally receives monosynaptic EPSPs from three to six CBCO neurons, ARINs receive monosynaptic EPSPs from up to eight velocity-coding stretch-sensitive CBCO neurons. In addition, ARINs receive disynaptic inhibitory phasic inputs from stretch-sensitive CBCO afferents. Injection of a depolarizing current pulse into ARINs elicits a fast transient voltage-dependent depolarization. Its time to peak decreases, and its peak amplitude increases with increasing current intensity. ARINs likely are to be connected directly to Dep MNs. The synaptic delay between these nonspiking ARINs and Dep MNs is short (<2 ms) and constant. The postsynaptic EPSP amplitude increases with increasing current pulse intensity injected into ARIN. The dual sensory control (excitatory and inhibitory) makes it likely that ARIN represents a key element in reflex reversal control

Active Motor Neurons Potentiate Their Own Sensory Inputs via Glutamate-Induced Long-Term Potentiation

International audienceAdaptive motor control is based mainly on the processing and integration of proprioceptive feedback information. In crayfish walking leg, many of these operations are performed directly by the motor neurons (MNs), which are connected monosynapti-cally by sensory afferents (CBTs) originating from a chordotonal organ that encodes vertical limb movements. An in vitro preparation of the crayfish CNS was used to investigate a new control mechanism exerted directly by motor neurons on the sensory inputs themselves. Paired intracellular recordings demonstrated that, in the absence of any presynaptic sensory firing, the spiking activity of a leg MN is able long-lastingly to enhance the efficacy of the CBT-MN synapses. Moreover, this effect is specific to the activated MN because no changes were induced at the afferent synapses of a neighboring silent MN. We report evidence that long-term potentiation (LTP) of the monosynaptic EPSP involves a retrograde system of glutamate transmission from the postsynaptic MN, which induces the activation of a metabotropic glutamate receptor located presynaptically on the CBTs. We demonstrate that LTP at crayfish sensory-motor synapses results exclusively from the long-lasting enhancement of release of acetylcholine from presynaptic sensory af-ferent terminals, without inducing any modifications in postsyn-aptic MN properties. Our data indicate that this positive feedback control represents a functional mechanism that may play a key role in the auto-organization of sensory-motor networks

Efferent controls in crustacean mechanoreceptors

International audienceSince the 1960s it has been known that central neural networks can elaborate motor patterns in the absence of any sensory feedback. However, sensory and neuromodulatory inputs allow the animal to adapt the motor command to the actual mechanical configuration or changing needs. Many studies in invertebrates, particularly in crustacea, have described several mechanisms of sensory-motor integration and have shown that part of this integration was supported by the efferent control of the mechanosensory neurons themselves. In this article, we review the findings that support such an efferent control of mechanosensory neurons in crustacea. Various types of crustacean proprioceptors feeding information about joint movements and strains to central neural networks are considered, together with evidence of efferent controls exerted on their sensory neurons. These efferent controls comprise (1) the neurohormonal modulation of the coding properties of sensory neurons by bioamines and peptides; (2) the presynaptic inhibition of sensory neurons by GABA, glutamate and histamine; and (3) the long-term potentiation of sensory-motor synapses by glutamate. Several of these mechanisms can coexist on the same sensory neuron, and the functional significance of such multiple modulations is discussed

Supraspinal control of locomotion

International audienceLocomotion is a basic motor function generated and controlled by genetically defined neuronal networks. The pattern of muscle synergies is generated in the spinal cord, whereas neural centers located above the spinal cord in the brainstem and the forebrain are essential for initiating and controlling locomotor movements. One such locomotor control center in the brainstem is the mesencephalic locomotor region (MLR), first discovered in cats and later found in all vertebrate species tested to date. Over the last years, we have investigated the cellular mechanisms by which this locomotor region operates in lampreys. The lamprey MLR is a well-circumscribed region located at the junction between the midbrain and hindbrain. Stimulation of the MLR induces locomotion with an intensity that increases with the stimulation strength. Glutamatergic and cholinergic monosynaptic inputs from the MLR are responsible for excitation of reticulospinal (RS) cells that in turn activate the spinal locomotor networks. The inputs are larger in the rostral than in the caudal hindbrain RS cells. MLR stimulation on one side elicits symmetrical excitatory inputs in RS cells on both sides, and this is linked to bilateral projections of the MLR to RS cells. In addition to its inputs to RS cells, the MLR activates a well-defined group of muscarinoceptive cells in the brainstem that feeds back strong excitation to RS cells in order to amplify the locomotor output. Finally, the MLR gates sensory inputs to the brainstem through a muscarinic mechanism. It appears therefore that the MLR not only controls locomotor activity but also filters sensory influx during locomotion

How Does the Central Nervous System for Posture and Locomotion Cope With Damage-Induced Neural Asymmetry?

In most vertebrates, posture and locomotion are achieved by a biomechanical apparatus whose effectors are symmetrically positioned around the main body axis. Logically, motor commands to these effectors are intrinsically adapted to such anatomical symmetry, and the underlying sensory-motor neural networks are correspondingly arranged during central nervous system (CNS) development. However, many developmental and/or life accidents may alter such neural organization and acutely generate asymmetries in motor operation that are often at least partially compensated for over time. First, we briefly present the basic sensory-motor organization of posturo-locomotor networks in vertebrates. Next, we review some aspects of neural plasticity that is implemented in response to unilateral central injury or asymmetrical sensory deprivation in order to substantially restore symmetry in the control of posturo-locomotor functions. Data are finally discussed in the context of CNS structure-function relationship

A neuronal substrate for a state-dependent modulation of sensory inputs in the brainstem

International audienceCentral networks modulate sensory transmission during motor behavior. Sensory inputs may thus have distinct impacts according to the state of activity of the central networks. Using an in-vitro isolated lamprey brainstem preparation, we investigated whether a brainstem locomotor center, the mesencephalic locomotor region (MLR), modulates sensory transmission. The synaptic responses of brainstem reticulospinal (RS) cells to electrical stimulation of the sensory trigeminal nerve were recorded before and after electrical stimulation of the MLR. The RS cell synaptic responses were significantly reduced by MLR stimulation and the reduction of the response increased with the stimulation intensity of the MLR. Bath perfusion of atropine prevented the depression of sensory transmission, indicating that muscarinic receptor activation is involved. Previous studies have shown that, upon stimulation of the MLR, behavioral activity switches from a resting state to an active-locomotor state. Therefore, our results suggest that a state-dependent modulation of sensory transmission to RS cells occurs in the behavioral context of locomotion and that muscarinic inputs from the MLR are involved

Metamorphosis-Induced Changes in the Coupling of Spinal Thoraco-Lumbar Motor Outputs During Swimming in Xenopus laevis

International audienceBeyeler A, Métais C, Combes D, Simmers J, Le Ray D. Metamorphosis induced changes in the coupling of spinal thoraco-lumbar motor outputs during swimming in Xenopus laevis. Anuran metamorphosis includes a complete remodeling of the animal's biomechanical apparatus, requiring a corresponding functional reorganization of underlying central neural circuitry. This involves changes that must occur in the coordination between the motor outputs of different spinal segments to harmonize locomotor and postural functions as the limbs grow and the tail regresses. In premetamorphic Xenopus laevis tadpoles, axial motor output drives rostrocaudally propagating segmental myotomal contractions that generate propulsive body undulations. During metamorphosis, the anterior axial musculature of the tadpole progressively evolves into dorsal muscles in the postmetamorphic froglet in which some of these back muscles lose their implicit locomotor function to serve exclusively in postural control in the adult. To understand how locomotor and postural systems interact during locomotion in juvenile Xenopus, we have investigated the coordination between postural back and hindlimb muscle activity during free forward swimming. Axial/ dorsal muscles, which contract in bilateral alternation during undulatory swimming in premetamorphic tadpoles, change their left-right coordination to become activated in phase with bilaterally synchronous hindlimb extensions in locomoting juveniles. Based on in vitro electrophysiologi-cal experiments as well as specific spinal lesions in vivo, a spinal cord region was delimited in which propriospinal interactions are directly responsible for the coordination between leg and back muscle contractions. Our findings therefore indicate that dynamic postural adjustments during adult Xenopus locomotion are mediated by local intraspinal pathways through which the lumbar generator for hindlimb propulsive kicking provides caudorostral commands to thoracic spinal circuitry controlling the dorsal trunk musculature

Heterosynaptic metaplastic regulation of synaptic efficacy in CA1 pyramidal neurons of rat hippocampus

International audienceThe induction threshold, and the magnitude and direction of changes in synaptic plasticity may depend on the previous history of neuronal activity. This phenomenon, termed "metaplasticity," could play an important role in integration processes by coordinating the modulation of synapses. Although metaplasticity has been analyzed extensively, its underlying cellular mechanisms remain largely unknown. Using in vitro electrophysiological and computer simulation approaches, we investigated the contribution of the slow Ca 2؉-dependent afterhyperpolariza-tion (sAHP) in the metaplastic control of the induction of long-term potentiation (LTP) at convergent CA3-CA1 pyramidal neuron synapses. We report that classical conditioning protocols may lead to the simultaneous induction of a sustained homosynaptic LTP and a potentiation of the sAHP that endured Ϸ1 h. The sAHP potentiation dramatically altered the spike responses of the CA1 pyramidal neuron. Of particular interest was the reduction of the CA1 neuron excitability and, consequently, of the capacity of a nonpotentiated synaptic input to elicit spikes while the sAHP was potentiated. This reduction in excitability temporarily prevented nonpotentiated synaptic inputs to exhibit an LTP induced by presynaptic tetanization. This metaplasticity was strongly resistant to increases in the magnitude of synaptic tetanization protocols. We propose that this het-erosynaptic metaplasticity, mediated by intrinsic cellular mechanisms, triggered by brief periods of activity, and relying on changes of a slow Ca 2؉-activated K ؉ current, may contribute to adjusting the efficacy of synaptic connections and shaping network behavior to regulate integration processes