Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1G93A motoneurons.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin ) E17.5 MNs from the SOD1G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild-type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD-like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri-somatic inhibitory terminals in SOD1G93A MNs compared to WT littermates. Putative fast ALS-vulnerable MNs with low Rin are therefore lacking functional inhibition at the near-term prenatal stage. KEY POINTS: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near-term stage.

Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut in crayfish.

Axons deprived of their nucleus degenerate within a few days in mammals but survive for several months in crustaceans. However, it is not known whether central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity. To assess this, we used peripheral axotomy, which removes their nuclei combined with electrophysiology techniques and electron microscopy imaging. We report the following. (1) Electron microscopy analysis confirms previous observations that glial cell nuclei present in the sensory nerve proliferate and migrate to axon tubes, where they form close contacts with surviving axons. (2) After peripheral axotomy performed in vivo on the coxo-basipodite chordotonal organ (CBCO), the sensory nerve does not convey any sensory message, but antidromic volleys are observed. (3) Central synaptic transmission from the CBCO to motoneurons (MNs) progressively declines over 200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of disynaptic inhibitory transmission persists up to 6 months). After 200 days, no transmission is observed. (4) However, this total loss is apparent only because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials and then excitatory post-synaptic potentials. (5) The loss of synaptic transmission can be prevented by in vivo chronic sensory nerve stimulation. (6) Using simulations based on the geometric arrangements of synapses of the monosynaptic excitatory transmission and disynaptic inhibitory pathways, we show that antidromic activity in the CBCO nerve could play a role in the maintenance of synaptic function of inhibitory pathways to MNs, but not monosynaptic excitatory transmission to MNs. Our study confirms the deep changes in glial nuclei observed in axons deprived of their nucleus. We further show that the machinery for spike conduction and synaptic release persists for several months, even if there is no longer any activity. Indeed, we were able to restore, with electrical activity, spike conduction and synaptic function after long silent periods (>6 months).

Sensory substitution of elbow proprioception to improve myoelectric control of upper limb prosthesis: experiment on healthy subjects and amputees.

BACKGROUND: Current myoelectric prostheses lack proprioceptive information and rely on vision for their control. Sensory substitution is increasingly developed with non-invasive vibrotactile or electrotactile feedback, but most systems are designed for grasping or object discriminations, and few were tested for online control in amputees. The objective of this work was evaluate the effect of a novel vibrotactile feedback on the accuracy of myoelectric control of a virtual elbow by healthy subjects and participants with an upper-limb amputation at humeral level. METHODS: Sixteen, healthy participants and 7 transhumeral amputees performed myoelectric control of a virtual arm under different feedback conditions: vision alone (VIS), vibration alone (VIB), vision plus vibration (VIS + VIB), or no feedback at all (NO). Reach accuracy was evaluated by angular errors during discrete as well as back and forth movements. Healthy participants' workloads were assessed with the NASA-TLX questionnaire, and feedback conditions were ranked according to preference at the end of the experiment. RESULTS: Reach errors were higher in NO than in VIB, indicating that our vibrotactile feedback improved performance as compared to no feedback. Conditions VIS and VIS+VIB display similar levels of performance and produced lower errors than in VIB. Vision remains therefore critical to maintain good performance, which is not ameliorated nor deteriorated by the addition of vibrotactile feedback. The workload associated with VIB was higher than for VIS and VIS+VIB, which did not differ from each other. 62.5% of healthy subjects preferred the VIS+VIB condition, and ranked VIS and VIB second and third, respectively. CONCLUSION: Our novel vibrotactile feedback improved myoelectric control of a virtual elbow as compared to no feedback. Although vision remained critical, the addition of vibrotactile feedback did not improve nor deteriorate the control and was preferred by participants. Longer training should improve performances with VIB alone and reduce the need of vision for close-loop prosthesis control.

Biological Plausibility of Arm Postures Influences the Controllability of Robotic Arm Teleoperation.

OBJECTIVE: We investigated how participants controlling a humanoid robotic arm's 3D endpoint position by moving their own hand are influenced by the robot's postures. We hypothesized that control would be facilitated (impeded) by biologically plausible (implausible) postures of the robot. BACKGROUND: Kinematic redundancy, whereby different arm postures achieve the same goal, is such that a robotic arm or prosthesis could theoretically be controlled with less signals than constitutive joints. However, congruency between a robot's motion and our own is known to interfere with movement production. Hence, we expect the human-likeness of a robotic arm's postures during endpoint teleoperation to influence controllability. METHOD: Twenty-two able-bodied participants performed a target-reaching task with a robotic arm whose endpoint's 3D position was controlled by moving their own hand. They completed a two-condition experiment corresponding to the robot displaying either biologically plausible or implausible postures. RESULTS: Upon initial practice in the experiment's first part, endpoint trajectories were faster and shorter when the robot displayed human-like postures. However, these effects did not persist in the second part, where performance with implausible postures appeared to have benefited from initial practice with plausible ones. CONCLUSION: Humanoid robotic arm endpoint control is impaired by biologically implausible joint coordinations during initial familiarization but not afterwards, suggesting that the human-likeness of a robot's postures is more critical for control in this initial period. APPLICATION: These findings provide insight for the design of robotic arm teleoperation and prosthesis control schemes, in order to favor better familiarization and control from their users.

Shoulder kinematics plus contextual target information enable control of multiple distal joints of a simulated prosthetic arm and hand.

BACKGROUND: Prosthetic restoration of reach and grasp function after a trans-humeral amputation requires control of multiple distal degrees of freedom in elbow, wrist and fingers. However, such a high level of amputation reduces the amount of available myoelectric and kinematic information from the residual limb. METHODS: To overcome these limits, we added contextual information about the target's location and orientation such as can now be extracted from gaze tracking by computer vision tools. For the task of picking and placing a bottle in various positions and orientations in a 3D virtual scene, we trained artificial neural networks to predict postures of an intact subject's elbow, forearm and wrist (4 degrees of freedom) either solely from shoulder kinematics or with additional knowledge of the movement goal. Subjects then performed the same tasks in the virtual scene with distal joints predicted from the context-aware network. RESULTS: Average movement times of 1.22s were only slightly longer than the naturally controlled movements (0.82 s). When using a kinematic-only network, movement times were much longer (2.31s) and compensatory movements from trunk and shoulder were much larger. Integrating contextual information also gave rise to motor synergies closer to natural joint coordination. CONCLUSIONS: Although notable challenges remain before applying the proposed control scheme to a real-world prosthesis, our study shows that adding contextual information to command signals greatly improves prediction of distal joint angles for prosthetic control.

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Correction to: Effect of vibration characteristics and vibror arrangement on the tactile perception of the upper arm in healthy subjects and upper limb amputees.

The original article [1] contained an error whereby the captions to Fig. 3 and Fig. 8 were mistakenly interchanged.

Implication of 5-HT in the Dysregulation of Chloride Homeostasis in Prenatal Spinal Motoneurons from the G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. The early presymptomatic onset of abnormal processes is indicative of cumulative defects that ultimately lead to a late manifestation of clinical symptoms. It remains of paramount importance to identify the primary defects that underlie this condition and to determine how these deficits lead to a cycle of deterioration. We recently demonstrated that prenatal E17.5 lumbar spinal motoneurons (MNs) from SOD1G93A mice exhibit a KCC2-related alteration in chloride homeostasis, i.e., the EGABAAR is more depolarized than in WT littermates. Here, using immunohistochemistry, we found that the SOD1G93A lumbar spinal cord is less enriched with 5-HT descending fibres than the WT lumbar spinal cord. High-performance liquid chromatography confirmed the lower level of the monoamine 5-HT in the SOD1G93A spinal cord compared to the WT spinal cord. Using ex vivo perforated patch-clamp recordings of lumbar MNs coupled with pharmacology, we demonstrated that 5-HT strongly hyperpolarizes the EGABAAR by interacting with KCC2. Therefore, the deregulation of the interplay between 5-HT and KCC2 may explain the alteration in chloride homeostasis detected in prenatal SOD1G93A MNs. In conclusion, 5-HT and KCC2 are two likely key factors in the presymptomatic phase of ALS, particular in familial ALS involving the SOD1G93A mutation.

Serotonin in Animal Cognition and Behavior.

Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions. In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.

Do arthropods feel anxious during molts?

The molting process of arthropods, chiefly controlled by ecdysteroids, is generally considered very stressful. Our previous investigations have shown that crayfish, after having experienced stressful situations, display anxiety-like behavior (ALB), characterized by aversion to light in a dark/light plus-maze (DLPM). In the present experiments, the spontaneous exploratory behavior of isolated crayfish was analyzed in a DLPM at different stages of their molt cycle. All tested animals displayed transitory aversion to light similar to ALB, before and, mostly, after molting, but not during inter-molt. Injection of ecdysteroids into inter-molt animals elicited ALB after a delay of 4 days, suggesting a long-term, possibly indirect, hormonal effect. Importantly, ecdysteroid-induced ALB was suppressed by the injection of an anxiolytic benzodiazepine. Thus, molts and their hormonal control impose internal stress on crayfish, leading to aversion behavior that has the main characteristics of anxiety. These observations are possibly generalizable to many other arthropods.

Effect of vibration characteristics and vibror arrangement on the tactile perception of the upper arm in healthy subjects and upper limb amputees.

BACKGROUND: Vibrotactile stimulation is a promising venue in the field of prosthetics to retrain sensory feedback deficits following amputation. Discrimination is well established at the forearm level but not at the upper arm level. Moreover, the effects of combining vibration characteristics such as duration and intensity has never been investigated. METHOD: We conducted experiments on spatial discrimination (experiment 1) and tactile intensity perception (experiment 2), using 9 combinations of 3 intensities and 3 durations of vibror stimulations device. Those combinations were tested under 4 arrangements with an array of 6 vibrors. In both experiments, linear orientation aligned with the upper arm longitudinal axis were compared to circular orientation on the upper arm circumference. For both orientations, vibrors were placed either with 3cm space between the center of 2 vibrors or proportionally to the length or the circumference of the subject upper arm. Eleven heathy subjects underwent the 2 experiments and 7 amputees (humeral level) participated in the spatial discrimination task with the best arrangement found. RESULTS: Experiment 1 revealed that circular arrangements elicited better scores than the linear ones. Arrangements with vibrors spaced proportionally elicited better scores (up to 75% correct) than those with 3 cm spacing. Experiment 2, showed that the perceived intensity of the vibration increases with the intensity of the vibrors' activation, but also with their duration of activation. The 7 patients obtained high scores (up to 91.67% correct) with the circular proportional (CP) arrangement. DISCUSSION: These results highlight that discrete and short vibrations can be well discriminated by healthy subjects and people with an upper limb amputation. These new characteristics of vibrations have great potential for future sensory substitution application in closed-loop prosthetic control.

Evidence for altered dendritic spine compartmentalization in Alzheimer's disease and functional effects in a mouse model.

Alzheimer's disease (AD) is associated with a progressive loss of synapses and neurons. Studies in animal models indicate that morphological alterations of dendritic spines precede synapse loss, increasing the proportion of large and short ("stubby") spines. Whether similar alterations occur in human patients, and what their functional consequences could be, is not known. We analyzed biopsies from AD patients and APP x presenilin 1 knock-in mice that were previously shown to present a loss of pyramidal neurons in the CA1 area of the hippocampus. We observed that the proportion of stubby spines and the width of spine necks are inversely correlated with synapse density in frontal cortical biopsies from non-AD and AD patients. In mice, the reduction in the density of synapses in the stratum radiatum was preceded by an alteration of spine morphology, with a reduction of their length and an enlargement of their neck. Serial sectioning examined with electron microscopy allowed us to precisely measure spine parameters. Mathematical modeling indicated that the shortening and widening of the necks should alter the electrical compartmentalization of the spines, leading to reduced postsynaptic potentials in spine heads, but not in soma. Accordingly, there was no alteration in basal synaptic transmission, but long-term potentiation and spatial memory were impaired. These results indicate that an alteration of spine morphology could be involved in the early cognitive deficits associated with AD.

Alteration of size perception: serotonin has opposite effects on the aggressiveness of crayfish confronting either a smaller or a larger rival.

We injected serotonin (5-HT) into adult male crayfish before pairing them with size-matched non-injected competitors, and observed dyadic agonistic interactions. Paradoxically, 5-HT elicited opposite behavioral responses if the injected animal was opposed by a smaller or larger rival: the level of aggressiveness of the injected crayfish was higher when facing a larger rival but lower when facing a smaller rival. Our results indicate that the effects of 5-HT on aggressiveness are dependent on the perception of the relative size difference of the opponent. In both cases, however, 5-HT significantly delayed the decision to retreat. We conclude that 5-HT does not primarily act on aggressiveness but rather on the brain centers that integrate risk assessment and/or decision making, which then modulate the aggressive response. Our findings support a reinterpretation of the role of 5-HT in crustacean agonistic behavior that may be of interest for studies of other animals.

Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output.

The axon initial segment (AIS) is a structure at the start of the axon with a high density of sodium and potassium channels that defines the site of action potential generation. It has recently been shown that this structure is plastic and can change its position along the axon, as well as its length, in a homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory nucleus lead to a lengthening of the AIS and an increase in neuronal excitability. On the other hand, a long-term increase in activity in dissociated rat hippocampal neurons results in an outward movement of the AIS and a decrease in the cell's excitability. Here, we investigated whether the AIS is capable of undergoing structural plasticity in rat hippocampal organotypic slices, which retain the diversity of neuronal cell types present at postnatal ages, including chandelier cells. These interneurons exclusively target the AIS of pyramidal neurons and form rows of presynaptic boutons along them. Stimulating individual CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components of the axo-axonic synapses did not change position after AIS relocation. We used computational modeling to explore the functional consequences of this partial mismatch and found that it allows the GABAergic synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability. We propose that this spatial arrangement is the optimal configuration for a homeostatic response to long-term stimulation.

Cav1.2 and Cav1.3 L-type calcium channels independently control short- and long-term sensitization to pain.

KEY POINTS: L-type calcium channels in the CNS exist as two subunit forming channels, Cav1.2 and Cav1.3, which are involved in short- and long-term plasticity. We demonstrate that Cav1.3 but not Cav1.2 is essential for wind-up. These results identify Cav1.3 as a key conductance responsible for short-term sensitization in physiological pain transmission. We confirm the role of Cav1.2 in a model of long-term plasticity associated with neuropathic pain. Up-regulation of Cav1.2 and down-regultation of Cav1.3 in neuropathic pain underlies the switch from physiology to pathology. Finally, the results of the present study reveal that therapeutic targeting molecular pathways involved in wind-up may be not relevant in the treatment of neuropathy. ABSTRACT: Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short-term sensitization can be monitored through the study of wind-up. Wind-up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post-synaptic L-type calcium channels. In the dorsal horn of the spinal cord, two L-type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind-up, whereas Cav1.2 is not and that synaptically triggered wind-up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind-up was decreased. These results were confirmed with our model when adapting Cav1.3 conductance to the changes observed after SNL. Finally, our mathematical approach predicts that, although wind-up amplitude is decreased in SNL, plateau potentials are not altered, suggesting that plateau and wind-up are not fully equivalent. Wind-up and long-term hyperexcitability of DHNs are differentially controlled by Cav1.2 and Cav1.3, therefore confirming that short- and long-term sensitization are two different phenomena triggered by distinct mechanisms.

The effect of sensory feedback on crayfish posture and locomotion: I. Experimental analysis of closing the loop.

The effect of proprioceptive feedback on the control of posture and locomotion was studied in the crayfish Procambarus clarkii (Girard). Sensory and motor nerves of an isolated crayfish thoracic nerve cord were connected to a computational neuromechanical model of the crayfish thorax and leg. Recorded levator (Lev) and depressor (Dep) nerve activity drove the model Lev and Dep muscles to move the leg up and down. These movements released and stretched a model stretch receptor, the coxobasal chordotonal organ (CBCO). Model CBCO length changes drove identical changes in the real CBCO; CBCO afferent responses completed the feedback loop. In a quiescent preparation, imposed model leg lifts evoked resistance reflexes in the Dep motor neurons that drove the leg back down. A muscarinic agonist, oxotremorine, induced an active state in which spontaneous Lev/Dep burst pairs occurred and an imposed leg lift excited a Lev assistance reflex followed by a Lev/Dep burst pair. When the feedback loop was intact, Lev/Dep burst pairs moved the leg up and down rhythmically at nearly three times the frequency of burst pairs when the feedback loop was open. The increased rate of rhythmic bursting appeared to result from the positive feedback produced by the assistance reflex.

The effect of sensory feedback on crayfish posture and locomotion: II. Neuromechanical simulation of closing the loop.

Neuromechanical simulation was used to determine whether proposed thoracic circuit mechanisms for the control of leg elevation and depression in crayfish could account for the responses of an experimental hybrid neuromechanical preparation when the proprioceptive feedback loop was open and closed. The hybrid neuromechanical preparation consisted of a computational model of the fifth crayfish leg driven in real time by the experimentally recorded activity of the levator and depressor (Lev/Dep) nerves of an in vitro preparation of the crayfish thoracic nerve cord. Up and down movements of the model leg evoked by motor nerve activity released and stretched the model coxobasal chordotonal organ (CBCO); variations in the CBCO length were used to drive identical variations in the length of the live CBCO in the in vitro preparation. CBCO afferent responses provided proprioceptive feedback to affect the thoracic motor output. Experiments performed with this hybrid neuromechanical preparation were simulated with a neuromechanical model in which a computational circuit model represented the relevant thoracic circuitry. Model simulations were able to reproduce the hybrid neuromechanical experimental results to show that proposed circuit mechanisms with sensory feedback could account for resistance reflexes displayed in the quiescent state and for reflex reversal and spontaneous Lev/Dep bursting seen in the active state.

Serotonin, but not dopamine, controls the stress response and anxiety-like behavior in the crayfish Procambarus clarkii.

In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3- to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB.

Neural circuit reconfiguration by social status.

The social rank of an animal is distinguished by its behavior relative to others in its community. Although social-status-dependent differences in behavior must arise because of differences in neural function, status-dependent differences in the underlying neural circuitry have only begun to be described. We report that dominant and subordinate crayfish differ in their behavioral orienting response to an unexpected unilateral touch, and that these differences correlate with functional differences in local neural circuits that mediate the responses. The behavioral differences correlate with simultaneously recorded differences in leg depressor muscle EMGs and with differences in the responses of depressor motor neurons recorded in reduced, in vitro preparations from the same animals. The responses of local serotonergic interneurons to unilateral stimuli displayed the same status-dependent differences as the depressor motor neurons. These results indicate that the circuits and their intrinsic serotonergic modulatory components are configured differently according to social status, and that these differences do not depend on a continuous descending signal from higher centers.

Spatial segregation of excitatory and inhibitory effects of 5-HT on crayfish motoneurons.

Altering neuronal membrane properties, including input resistance, is a key modulatory mechanism for changing neural activity patterns. The effect of membrane currents generated by either synaptic or voltage-dependent channels directly depends on neuron input resistance. We found that local application of serotonin to different regions of identified motoneurons (MNs) of the postural/walking network of isolated crayfish produced different changes in input resistance. Puff-applied 5-HT in the periphery of the initial segment produced exclusively inhibitory responses. In contrast, when 5-HT was puff-applied on the central arbor of the same depressor (Dep) MN, exclusively depolarizing responses were obtained. Both inhibitory and excitatory responses were direct because they persisted in low-calcium saline. We found numerous close appositions between 5-HT-immunoreactive processes and the initial segment of dextran-rhodamine-filled Dep MNs. In contrast, almost no close apposition sites were found in Dep MN arbor. It seems that the 5-HT controls the level of excitability of postural network MNs by two mechanisms acting at two different sites: inhibitory responses (consistent with an action involving opening of K(+) channels) occur in the initial segment region and may involve classic synaptic transmission, whereas depolarizing responses (consistent with an action involving closing of K(+) channels) occur on MN branches via apparent paracrine effects.