Neuromodulation via conditional release of endocannabinoids in the spinal locomotor network

Endocannabinoids act as retrograde signals to modulate synaptic transmission. Little is known, however, about their significance in integrated network activity underlying motor behavior. We have examined the physiological effects of endocannabinoids in a neuronal network underlying locomotor behavior using the isolated lamprey spinal cord. Our results show that endocannabinoids are released during locomotor activity and participate in setting the baseline burst rate. They are released in response to mGluR1 activation and act as retrograde messengers. This conditional release of endocannabinoids can transform motoneurons and crossing interneurons into modulatory neurons by enabling them to regulate their inhibitory synaptic inputs and thus contribute to the modulation of the locomotor burst frequency. These results provide evidence that endocannabinoid retrograde signaling occurs within the locomotor network and contributes to motor pattern generation and regulation in the spinal cord.     

A hemicord locomotor network of excitatory interneurons: a simulation study

Locomotor burst generation is simulated using a full-scale network model of the unilateral excitatory interneuronal population. Earlier small-scale models predicted that a population of excitatory neurons would be sufficient to produce burst activity, and this has recently been experimentally confirmed. Here we simulate the hemicord activity induced under various experimental conditions, including pharmacological activation by NMDA and AMPA as well as electrical stimulation. The model network comprises a realistic number of cells and synaptic connectivity patterns. Using similar distributions of cellular and synaptic parameters, as have been estimated experimentally, a large variation in dynamic characteristics like firing rates, burst, and cycle durations were seen in single cells. On the network level an overall rhythm was generated because the synaptic interactions cause partial synchronization within the population. This network rhythm not only emerged despite the distributed cellular parameters but relied on this variability, in particular, in reproducing variations of the activity during the cycle and showing recruitment in interneuronal populations. A slow rhythm (0.4–2 Hz) can be induced by tonic activation of NMDA-sensitive channels, which are voltage dependent and generate depolarizing plateaus. The rhythm emerges through a synchronization of bursts of the individual neurons. A fast rhythm (4–12 Hz), induced by AMPA, relies on spike synchronization within the population, and each burst is composed of single spikes produced by different neurons. The dynamic range of the fast rhythm is limited by the ability of the network to synchronize oscillations and depends on the strength of synaptic connections and the duration of the slow after hyperpolarization. The model network also produces prolonged bouts of rhythmic activity in response to brief electrical activations, as seen experimentally. The mutual excitation can sustain long-lasting activity for a realistic set of synaptic parameters. The bout duration depends on the strength of excitatory synaptic connections, the level of persistent depolarization, and the influx of Ca²⁺ ions and activation of Ca²⁺-dependent K⁺ current.     

Flexibility in the patterning and control of axial locomotor networks in lamprey

In lower vertebrates, locomotor burst generators for axial muscles generally produce unitary bursts that alternate between the two sides of the body. In lamprey, a lower vertebrate, locomotor activity in the axial ventral roots of the isolated spinal cord can exhibit flexibility in the timings of bursts to dorsally-located myotomal muscle fibers versus ventrally-located myotomal muscle fibers. These episodes of decreased synchrony can occur spontaneously, especially in the rostral spinal cord where the propagating body waves of swimming originate. Application of serotonin, an endogenous spinal neurotransmitter known to presynaptically inhibit excitatory synapses in lamprey, can promote decreased synchrony of dorsal-ventral bursting. These observations suggest the possible existence of dorsal and ventral locomotor networks with modifiable coupling strength between them. Intracellular recordings of motoneurons during locomotor activity provide some support for this model. Pairs of motoneurons innervating myotomal muscle fibers of similar ipsilateral dorsoventral location tend to have higher correlations of fast synaptic activity during fictive locomotion than do pairs of motoneurons innervating myotomes of different ipsilateral dorsoventral locations, suggesting their control by different populations of premotor interneurons. Further, these different motoneuron pools receive different patterns of excitatory and inhibitory inputs from individual reticulospinal neurons, conveyed in part by different sets of premotor interneurons. Perhaps, then, the locomotor network of the lamprey is not simply a unitary burst generator on each side of the spinal cord that activates all ipsilateral body muscles simultaneously. Instead, the burst generator on each side may comprise at least two coupled burst generators, one controlling motoneurons innervating dorsal body muscles and one controlling motoneurons innervating ventral body muscles. The coupling strength between these two ipsilateral burst generators may be modifiable and weakening when greater swimming maneuverability is required. Variable coupling of intrasegmental burst generators in the lamprey may be a precursor to the variable coupling of burst generators observed in the control of locomotion in the joints of limbed vertebrates.     

Activity-dependent modulation of adaptation produces a constant burst proportion in a model of the lamprey spinal locomotor generator

The neuronal network underlying lamprey swimming has stimulated extensive modelling on different levels of abstraction. The lamprey swims with a burst frequency ranging from 0.3 to 8–10 Hz with a rostro-caudal lag between bursts in each segment along the spinal cord. The swimming motor pattern is characterized by a burst proportion that is independent of burst frequency and lasts around 30%–40% of the cycle duration. This also applies in preparations in which the reciprocal inhibition in the spinal cord between the left and right side is blocked. A network of coupled excitatory neurons producing hemisegmental oscillations may form the basis of the lamprey central pattern generator (CPG). Here we explored how such networks, in principle, could produce a large frequency range with a constant burst proportion. The computer simulations of the lamprey CPG use simplified, graded output units that could represent populations of neurons and that exhibit adaptation. We investigated the effect of an active modulation of the degree of adaptation of the CPG units to accomplish a constant burst proportion over the whole frequency range when, in addition, each hemisegment is assumed to be self-oscillatory. The degree of adaptation is increased with the degree of stimulation of the network. This will make the bursts terminate earlier at higher burst rates, allowing for a constant burst proportion. Without modulated adaptation the network operates in a limited range of swimming frequencies due to a progressive increase of burst duration with increasing background stimulation. By introducing a modulation of the adaptation, a broad burst frequency range can be produced. The reciprocal inhibition is thus not the primary burst terminating factor, as in many CPG models, and it is mainly responsible for producing alternation between the left and right sides. The results are compared with the Morris-Lecar oscillator model with parameters set to produce a type A and type B oscillator, in which the burst durations stay constant or increase, respectively, when the background stimulation is increased. Here as well, burst duration can be controlled by modulation of the slow variable in a similar way as above. When oscillatory hemisegmental networks are coupled together in a chain a phase lag is produced. The production of a phase lag in chains of such oscillators is compared with chains of Morris-Lecar relaxation oscillators. Models relating to the intact versus isolated spinal cord preparation are discussed, as well as the role of descending inhibition. Received: 1 April 1997 / Accepted in revised form: 20 March 1998     

Modulation of Burst Frequency by Calcium-Dependent Potassium Channels in the Lamprey Locomotor System: Dependence of the Activity Level

It is crucial to determine the effects on the network level of a modulation of intrinsic membrane properties. The role calcium-dependent potassium channels, K_Ca, in the lamprey locomotor system has been investigated extensively. Earlier experimental studies have shown that apamin, which affects one type of K_Ca, increases the cycle duration of the locomotor network, due to effects on the burst termination. The effects of apamin were here larger when the network had a low level of activity (burst frequency 0.5 to 1 Hz) as compared to a higher rate (>2 Hz). By using a previously developed simulation model based on the lamprey locomotor network, we show that the model could account for the frequency dependence of the apamin modulation, if only the K_Ca conductance activated by Ca²⁺ entering during the action potential was altered and not the K_Ca conductance activated by Ca²⁺ entering through NMDA channels. The present simulation model of the spinal network in the lamprey can thus account for earlier experimental results with apamin on the network and cellular level that previously appeared enigmatic.     

Spinal Mechanisms in the Control of Lamprey Swimming

SYNOPSIS. The lamprey, an anguilliform fish, swims using lateralundulatory movement; a transverse wave passes backward, fromhead to tail, the amplitude of the wave increasing as it movestailward. The wave of muscle activity producing this movementtravels down the body faster than the mechanical wave. The wayin which certain features of anguilliform movement contributeto its efficiency have been described. The neural activity underlyingswimming is characterized by: 1) rhythmical alternation betweenthe two sides of a single segment; 2) a burst duration thatremains a constant proportion of the cycle time and is independentof the cycle frequency; 3) rostrocaudal phase lag that is constantand also independent of the cycle frequency. Local circuitsin the lamprey spinal cord can generate this locomotory patternin the absence of sensory feedback following activation of excitatoryamino acid receptors; the pattern is centrally generated. Ithas been hypothesized that the spinal central pattern generatorfor locomotion consists of a series of segmental burst generatorscoupled together by an intersegmental coordinating system. Theintersegmental coordinating system functions to keep the frequenciesof the oscillators along the cord constant and to provide theappropriate rostrocaudal phase lag. Mechanosensitive units withinthe spinal cord are sensitive to movement of the spinal cord\notochordand movement of the spinal cord/notochord can entrain the burstpattern. Entrainment occurs through movement-related feedbackonto neurons at the local level. The possible roles this movement-relatedfeedback plays during locomotion are discussed.     

Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey

Factors contributing to the production of a phase lag along chains of oscillatory networks consisting of Hodgkin-Huxley type neurons are analyzed by means of simulations. Simplified network configurations are explored consisting of the basic building blocks of the spinal central pattern generator (CPG) generating swimming in the lamprey. It consists of reciprocally coupled crossed inhibitory C interneurons and ipsilateral excitatory E interneurons that activate C neurons and other E neurons. Oscillatory activity in the model network can, in the simplest case, be produced by a pair of reciprocally coupled C interneurons oscillating through an escape mechanism. Different levels of tonic excitation drive the network over a wide burst frequency range. In this type of network, powerful frequency-regulating factors are the effective inhibition produced by the active side, in combination with the tendency of the inactive side to escape from the inhibition. These two mechanisms can be affected by several factors, e.g. spike frequency adaptation (calcium-dependent K(+) channels), N-methyl-D-aspartate membrane properties as well as presence of low-voltage activated calcium channels. A rostrocaudal phase lag can be produced either by extending the contralateral inhibitory projections or the ipsilateral excitatory projections relatively more in the caudal than the rostral direction, since both an increased inhibition and a phasic excitation slow down the receiving network. The phase lag becomes decreased if the length of the intersegmental projections is increased or if the projections are extended symmetrically in both the rostral and the caudal directions. The simulations indicate that the conditions in the ends of an oscillator chain may significantly affect sign, magnitude and constancy of the phase lag. Also, with short and relatively weak intersegmental connections, the network remains robust against perturbations as well as intrinsic frequency differences along the chain. The phase lag (percentage of cycle duration) increases, however, with burst frequency also when the coupling strength is comparatively weak. The results are discussed and compared with previous "phase pulling" models as well as relaxation oscillators.     

The role of putative glutamatergic neurons and their connections in the locomotor central pattern generator of the mollusk, Clione limacina

In the pteropod mollusk Clione limacina, locomotor rhythm is produced by the central pattern generator (CPG), due mainly to the activity of interneurons of groups 7 (active in the phase of the dorsal flexion of the wings) and 8 (active in the phase of the ventral flexion). Each of these groups excites the neurons active in the same phase of the locomotor cycle, and inhibits the neurons of the opposite phase. In this work, the nature of connections formed by group 7 interneurons was studied. Riluzole (2-amino-6-trifluoro-methoxybenzothiazole), which is known to inhibit the presynaptic release of glutamate, suppressed the action of the type 7 interneurons onto the follower neurons of the same and of the antagonistic phase of the locomotor cycle. The main pattern of rhythmic activity of CPG with alternation of two phases could be maintained after suppression of inhibitory connections from group 7 interneurons to antagonistic neurons. This suggests redundancy of the mechanisms controlling swimming rhythm generation, which ensures the reliable operation of the system.     

Modulation of swimming rhythmicity by 5-hydroxytryptamine during post-embryonic development in Xenopus laevis.

During the first 24 h of post-embryonic development in Xenopus laevis, a rapid change in the neural activity underlying swimming occurs in which the duration of ventral root discharge on each cycle increases from a single compound impulse to discrete bursts of activity. Moreover, this change in motor output progresses rostrocaudally, suggesting that it could result from the influence of a descending neural pathway upon the spinal rhythm-generating circuitry during early post-embryonic development. To begin to examine whether serotonergic neurons of brainstem raphe nuclei might have a role in this swimming development, we have studied the effects of 5-hydroxytryptamine (5HT) on fictive swimming in embryonic and larval animals. As previously demonstrated for other vertebrate locomotor rhythms, we find that bath-applied 5HT enhances the duration of motor activity on each cycle of larval fictive swimming. In addition, our results show that the sensitivity of the swimming rhythm to exogenous 5HT follows a strict rostrocaudal gradient. In young embryos (stages 32-36) 5HT does not affect the duration of ventral root impulses per cycle; by the time of hatching (stage 37/38), rostral but not caudal discharge is enhanced, and by stage 42 (24 h post-hatching) 5HT can increase motor burst durations along most of the length of the animal. These reversible changes induced by bath-applied 5HT closely resemble the normal rostrocaudal development of burst discharge during swimming in animals some 12 h older.(ABSTRACT TRUNCATED AT 250 WORDS)     

运动过程的网络逻辑——从离子通道到动物行为

为了揭示神经网络在脊椎动物运动中所行使的内在功能,作者开发了七鳃鳗这种低等脊椎动物模型。在这套系统中,不仅可以了解到运动模式生成网络以及激活此网络的命令系统,同时还可以在运动中研究方向控制系统和变向控制系统。七鳃鳗的神经系统有较少的神经元,而且运动行为中的不同运动模式可以由分离的神经系统所引发。模式生成神经网络包括同侧的谷氨酸能中间神经元和对侧的抑制性甘氨酸能中间神经元。网络中的突触连接、细胞膜特性和神经递质都也已经被鉴定。运动是由脑干区域的网状脊髓神经元所引起,而这些神经元又是被问脑和中脑分离的一些运动命令神经元群所控制。因此,运动行为最初是由这两个“运动核心”所启动。而这两个运动核心被基底神经节调控,基底神经节即时地做出判断是否允许下游的运动程序启动。在静止情况下基底神经节的输出核团维持对下游不同运动核心的抑制作用,反之则去除抑制活化运动核心。纹状体和苍白球被认为是这个运动抉择系统的主要部件。根据“霍奇金一贺胥黎”模型神经元开发了这套网络模型,不同的细胞具有各自相应的不同亚型的钠、钾、钙离子通道和钙依赖的钾通道。每个模型神经元拥有86个不同区域模块以及其对应的生物学功能,例如频率控制、超极化等等。然后根据已有实验证据,利用突触将不同的模型神经元相连。而系统中的10000个神经元大致和生物学网络上的细胞数量相当。突触数量为760000。突触类型有AMPA、NMDA、glycine型。有了这样大规模的模型,不仅可以模拟肌节与肌节之间的神经网络,还可以模拟到由基底神经节开始的行为起始部分。此外,这些网络模拟还被用于一个神经机械学模型来模拟包含有推进和方向控制部分的真实运动。     

Critical parameters of the spike trains in a cell assembly: coding of turn direction by the giant interneurons of the cockroach

Cockroaches (Periplaneta americana) respond to air displacement produced by an approaching predator by turning and running away. A set of 4 bilateral pairs of ventral giant interneurons is important in determining turn direction. Wind from a given side is known to produce more spikes, an earlier onset of the spike trains, and different fine temporal patterning, in the ipsilateral vs the contralateral set of these interneurons. Here we investigate which of these spike train parameters the cockroach actually uses to determine the direction it will turn.We delivered controlled wind puffs from the right front, together with intracellular injection of spike trains in a left ventral giant interneuron, under conditions where the animal could make normally directed turning movements of the legs and body. In trials where our stimuli caused the left side to give both the first spike and more total spikes than the right, but where our injected spike train included none of the normal fine temporal patterning, 92% of the evoked turns were to the rightopposite of normal (Figs. 4–6). In trials where the left side gave the first spike, but the right side gave more spikes, 100% of the turns were to the left-the normal direction (Figs. 8, 9). Comparable results were obtained when each of the left giant interneurons 1, 2 or 3 were electrically stimulated, and when either weak or stronger wind puffs were used. Stimulating a left giant interneuron electrically in the absence of a wind puff evoked an escape-like turn on 9% of the trials, and these were all to the right (Fig. 9).These results indicate that fine temporal patterning in the spike trains is not necessary, and information about which side gives the first spike is not sufficient, to determine turn direction. Rather, the key parameter appears to be relative numbers of action potentials in the left vs the right group of cells. These conclusions were supported by similar experiments in which extracellular stimulation of several left giant interneurons was paired with right wind (Figs. 11, 12).Abbreviations GI giant interneuron - vGI ventral giant interneuron - dGI dorsal giant interneuron - LY Lucifer yellow - CF carboxyfluorescein     

Pineal-dependent locomotor activity of lamprey,Lampetra japonica,measured in relation to LD cycle and circadian rhythmicity

Summary Locomotor activity of the river lamprey, Lampetra japonica, was investigated under a light-dark (LD 1212) cycle and under continuous dark conditions. Intact lampreys were entrained to the light:dark cycle. They were active mainly in the early half of the dark period and inactive in light period. The light:dark entrainment continued in 72.7% of lampreys after the removal of bilateral eyes, but additional pinealectomy made the entrainment disappear in all lampreys. When lampreys were pinealectomized with their eyes intact, light: dark entrainment was abolished in most cases. The results indicate that the pineal organ of the lamprey is a photoreceptive organ responsible for synchronizing locomotor activity to LD cycle. Under continuous dark conditions, the locomotor activity began to free-run with a period of 21.3 ± 0.9 h (mean ± SD, n = 53). This circadian rhythmicity was not affected by the removal of lateral eyes but was abolished by pinealectomy. The pineal organ appears to function as an oscillator, or as one of the oscillators, for the circadian locomotor rhythm of lampreys.Abbreviations DD continuous dark - LD light:dark     

Mathematical model of activity of spinal generators producing rhythmic movement

Different organizational arrangements of scratching and locomotor rhythm generators were simulated by a computer-aided mathematical model. A functional group of neurons (a hemicenter constructed on the basis of a stochastically arranged neuronal network) served as the basis for the generator. Several organizational arrangements of scratching and locomotor rhythm generators are considered: two hemicenters with reciprocal inhibitory connections and tonic excitatory influences on both; two hemicenters with inhibitory-excitatory connections and tonic excitatory influences on only one of these; circular structures consisting of more than two functional groups of neurons with excitatory and inhibitory connections between them. All these arrangements would allow for generation of rhythmic activity with a similar time course to that of scratching and locomotor rhythm. It was found that the transition from locomotor to scratching rhythm could be based on fairly simply organized effects on generator neurons. Principles possibly guiding the construction of spinal generators of scratching and locomotor movements are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 586–597, September–October, 1988.     

Membrane Potential Oscillations Produced by Excitatory Amino Acids in Isolated Spinal Neurons of the Lamprey Lampetra fluviatilis

Membrane potential (MP) oscillations produced by excitatory amino acids (EAA) have been studied in branching neurons isolated by an enzymatic-mechanical method from the lamprey spinal cord. It was shown that (1) all studied EAA (glutamate, kainate, NMDA, aspartate, and quisqualate) evoke an ion current and a short-term reversible depolarization in studied cells; (2) EAA added to perfusion solution may produce MP oscillations, with kinetic parameters and duration of the oscillation depending on the amino acid used (the most effective are kainate and NMDA, the least effective, quisqualate); (3) oscillations can be irregular (of the type of a synaptic noise or of a long-term plateau of depolarization with action potentials—AP) or regular, with frequency of 0.5–1.5 Hz. Amplitude of both oscillation types depends on MP level, frequency is more steady for each cell and less depends on MP. In 68 out of 128 studied cells, oscillations could be evoked, which indicates that a significant part of lamprey spinal neurons have intrinsic capability for MP oscillations and probably pacemaker properties. The functional role of oscillations can be different. They can take cells out from the profound inhibition state, synchronize activity of rhythm generation neurons and/or be the base for trigger signals (AP firing) sent by locomotor neuronal circuits to trunk muscles.     

Electrophysiological study of serotoninergic neuron Cl in the pteropod mollusk Clione

Functional characteristics of cerebral serotoninergic neuron Cl, axons of which terminate at the buccal ganglia [7], were investigated in the pteropod molluskClione. Stimulating neuron Cl induced activation of the feeding rhythm generator located in the buccal ganglia — an effect arising after a long latency and persisting for some tens of seconds once stimulation had ended. Neuron Cl receives feedback from buccal ganglion cells and this brings about periodic modulation in ganglia activity during the generation of feeding rhythm. Activity of neuron Cl is correlated with operation of the locomotor rhythm generator located in the pedal ganglia. The firing rate of Cl neurons increased upon activation of the locomotor generator (whether spontaneous or induced by stimulating certain command neurons). The correlation found between workings of the locomotor generator and activity of Cl neurons is thought to be one of the manifestations of feeding synergy involving simultaneous activation of the locomotor and buccal apparatus.Institute for Research on Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov State University, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 18–25, January–February, 1991.     

Sensory-evoked turning locomotion in red-eared turtles: kinematic analysis and electromyography

We examined the limb kinematics and motor patterns that underlie sensory-evoked turning locomotion in red-eared turtles. Intact animals were held by a band-clamp in a water-filled tank. Turn-swimming was evoked by slowly rotating turtles to the right or left via a motor connected to the shaft of the band-clamp. Animals executed sustained forward turn-swimming against the direction of the imposed rotation. We recorded video of turn-swimming and computer-analyzed the limb and head movements. In a subset of turtles, we also recorded electromyograms from identified limb muscles. Turning exhibited a stereotyped pattern of (1) coordinated forward swimming in the hindlimb and forelimb on the outer side of the turn, (2) back-paddling in the hindlimb on the inner side, (3) a nearly stationary, “braking” forelimb on the inner side, and (4) neck bending toward the direction of the turn. Reversing the rotation caused animals to switch the direction of their turns and the asymmetric pattern of right and left limb activities. Preliminary evidence suggested that vestibular inputs were sufficient to drive the behavior. Sensory-evoked turning may provide a useful experimental platform to examine the brainstem commands and spinal neural networks that underlie the activation and switching of different locomotor forms.     

Functional Organization of the Cardiac Ganglion of the Lobster, Homarus americanus

External recording and stimulation, techniques were used to determine which neurons and interactions are essential for production of the periodic burst discharge in the lobster cardiac ganglion. Burst activity can be modulated by brief single shocks applied to the four small cells, but not by similar stimulation of the five large cells, suggesting that normally one or more small cells primarily determine burst rate and duration. Repetitive electrical stimulation of large cells initiates spike activity in small cells, probably via excitatory synaptic and/or electrotonic connections which may normally act to prolong bursts and decrease burst rate. Transection of the ganglion can result in burst activity in small cells in the partial or complete absence of large cell spike activity, but large cells isolated from small cell excitatory synaptic input by transection or by application of dinitrophenol do not burst. Generally, transections which decrease excitatory feedback to small cells are accompanied by an increase in burst rate, but mean spike frequency over an entire burst cycle stabilizes at the original level within 10–30 min for various groups of cells whose spike-initiating sites are still intact. These and previous results suggest that the system is two layered: one or more small cells generate the burst pattern and impose it on the large cells which are the system's motorneurons.     

Circadian rhythms of locomotor activity and temperature selection in sleepy lizards, <Emphasis Type="Italic">Tiliqua rugosa</Emphasis>

This study examined whether the daily rhythms of locomotor activity and behavioural thermoregulation that have previously been observed in Australian sleepy lizards (Tiliqua rugosa) under field conditions are true circadian rhythms that persist in constant darkness (DD) and whether these rhythms show similar characteristics. Lizards held on laboratory thermal gradients in the Australian spring under the prevailing 12-hour light : dark (LD) cycle for 14 days displayed robust daily rhythms of behavioural thermoregulation and locomotor activity. In the 13-day period of DD that followed LD, most lizards exhibited free-running circadian rhythms of locomotor activity and behavioural thermoregulation. The predominant activity pattern displayed in LD was unimodal and this was retained in DD. While mean levels of skin temperature and locomotor activity were found to decrease from LD to DD, activity duration remained unchanged. The present results demonstrate for the first time that this species’ daily rhythm of locomotor activity is an endogenous circadian rhythm. Our results also demonstrate a close correlation between the circadian activity and thermoregulatory rhythms in this species indicating that the two rhythms are controlled by the same master oscillator(s). Future examination of seasonal aspects of these rhythms, may, however, cause this hypothesis to be modified.     

V3 spinal neurons establish a robust and balanced locomotor rhythm during walking

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.     

Multiple effects of an identified proprioceptor upon gastric pattern generation in spiny lobsters

1. Using deafferented preparations of the stomatogastric nervous system of spiny lobsters (Panulirus interruptus), we stimulated the central soma of the Anterior Gastric Receptor neuron (AGR) and analyzed sensorimotor integration in the gastric central pattern generator during rhythm production.
2. Driving AGR to spike tonically at lower frequencies (10–20 /s) accelerated the gastric rhythm, while higher frequencies (>30 /s) suppressed it.
3. Shorter spike trains in AGR evoked phase-dependent resetting of the gastric rhythm. Repetitive trains could entrain rhythms to both longer and shorter cycle periods. Some pattern-generating effects are consistent with effects upon the lateral gastric neuron, an influential member of the gastric mill network.
4. AGR affected the burst intensity of many of the gastric neurons in specific, complex ways. Some powerstroke motor neurons were excited because AGR activated excitatory, premotor interneurons (E cells). However, AGR also activated parallel, seemingly inhibitory inputs, whose mechanism remains unclear. Still other effects on motor neurons may be mediated partly by synaptic interactions within the network.
5. AGR adjusts the timing, strength and coordination of bursts in the motor innervation of all three teeth of the gastric mill, and may act to optimize the force of chewing to different consistencies of food.