A high-throughput method to deliver targeted optogenetic stimulation to moving C. elegans populations

We present a high-throughput optogenetic illumination system capable of simultaneous closed-loop light delivery to specified targets in populations of moving Caenorhabditis elegans. The instrument addresses three technical challenges: It delivers targeted illumination to specified regions of the animal’s body such as its head or tail; it automatically delivers stimuli triggered upon the animal’s behavior; and it achieves high throughput by targeting many animals simultaneously. The instrument was used to optogenetically probe the animal’s behavioral response to competing mechanosensory stimuli in the the anterior and posterior gentle touch receptor neurons. Responses to more than 43,418 stimulus events from a range of anterior–posterior intensity combinations were measured. The animal’s probability of sprinting forward in response to a mechanosensory stimulus depended on both the anterior and posterior stimulation intensity, while the probability of reversing depended primarily on the anterior stimulation intensity. We also probed the animal’s response to mechanosensory stimulation during the onset of turning, a relatively rare behavioral event, by delivering stimuli automatically when the animal began to turn. Using this closed-loop approach, over 9,700 stimulus events were delivered during turning onset at a rate of 9.2 events per worm hour, a greater than 25-fold increase in throughput compared to previous investigations. These measurements validate with greater statistical power previous findings that turning acts to gate mechanosensory evoked reversals. Compared to previous approaches, the current system offers targeted optogenetic stimulation to specific body regions or behaviors with many fold increases in throughput to better constrain quantitative models of sensorimotor processing.

This study resents a new targeted illumination method for the nematode Caenorhabditis elegans, allowing delivery of optogenetic stimulation to specific body parts of many animals at once, automatically triggered by the animals’ behavior.     

The synaptic origins of receptive field properties in the cricket cercal sensory system

Summary The regional distribution of cerebral glucose utilization, revealed by the¹⁴C-2DG technique, was compared between (i) toads after stimulus-specific long-term habituation of the orienting response toward a repeatedly presented prey dummy (habituation group) and (ii) non-habituated toads, readily orienting toward the repetitively presented prey stimulus (naive group). In the habituation group, the ventral medial pallium (vMP), a certain portion of the preoptic area (PO), and the dorsal hypothalamus (dHYP) showed a statistically significantincrease in¹⁴C-2DG-uptake;decrease was observed in the ventral layers of the optic tectum (vOT), a portion of the tegmental reticular formation (RET), the ventral cerebellum (vCB), and the striatum (STR). The results suggest that stimulus-specific long-term habituation of prey-catching affects both, components of thestimulus-response mediating circuit (e.g., involving OT), and structures extrinsic to it, (e.g., vMP, PO, dHYP), which may belong to amodulatory circuitry. Bilateral lesions to vMP strongly delay habituation. Our results are suggesting that damping of the adequate behavioral motor response during habituation involves active inhibitory processes of a modulatory system that develops in strength during stimulus repetition so as to suppress response output, which basically supports Sokolov's hypothesis (1975).Abbreviations A anterior dorsal thalamic nucleus - AL amygdala, lateral portion - dCB dorsal half of the cerebellum - vCB ventral half of the cerebellum - DP dorsal pallium - dHYP dorsal hypothalamus - pLP posterior half of the lateral pallium - Lpd lateral postero-dorsal thalamus - Lpv lateral postero-ventral thalamus - aMP anterior third of the medial pallium - dMP dorsal portion of the posterior medial pallium - vMP ventral two-third of the posterior medial pallium - MS medial septum - dOT dorsal layers of the optic tectum - vOT ventral layers of the optic tectum - P posterior thalamic nucleus - PO preoptic area - RET tegmental portion of the medial reticular formation - STR striatum, dorsal and ventral portion - vTEG ventral tegmentum     

A developmental analysis of spontaneous and reflexive reversals in the nematode Caenorhabditis elegans

Reversals of forward locomotion in the nematode Caenorhabditis elegans are thought to be mediated by a common neural circuit, the touch withdrawal circuit. Despite substantial neuroanatomical changes over post-embryonic development, one reversal behavior, the head-touch withdrawal reflex, does not appear to change over development (Chalfie and Sulston, 1981). The experiments reported here indicate that two other reversal behaviors, spontaneous reversals and the tap reversal reflex to vibratory stimuli, show developmental changes. Young adult animals showed higher frequencies of spontaneous reversals than all other developmental stages, while larval stages differed from adults in their pattern of responses to tap. Although animals of all stages reversed in response to touch, taps elicited both reversals and accelerations of forward movement. In response to single taps, larval stages reversed on approximately half the occasions; young adult and 4-day-old adults almost always reversed. Increasing stimulus magnitudes increased the probability of accelerations at all developmental stages, but larval stages showed fewer reversals and more accelerations than adults. The behavioral changes observed coincide with known periods of neuroanatomical change in the touch withdrawal circuit. The addition of a late-developing sensory neuron, AVM, is implicated in the behavioral differences between juveniles and adults.     

MAGI-1 Modulates AMPA Receptor Synaptic Localization and Behavioral Plasticity in Response to Prior Experience

It is well established that the efficacy of synaptic connections can be rapidly modified by neural activity, yet how the environment and prior experience modulate such synaptic and behavioral plasticity is only beginning to be understood. Here we show in C. elegans that the broadly conserved scaffolding molecule MAGI-1 is required for the plasticity observed in a glutamatergic circuit. This mechanosensory circuit mediates reversals in locomotion in response to touch stimulation, and the AMPA-type receptor (AMPAR) subunits GLR-1 and GLR-2, which are required for reversal behavior, are localized to ventral cord synapses in this circuit. We find that animals modulate GLR-1 and GLR-2 localization in response to prior mechanosensory stimulation; a specific isoform of MAGI-1 (MAGI-1L) is critical for this modulation. We show that MAGI-1L interacts with AMPARs through the intracellular domain of the GLR-2 subunit, which is required for the modulation of AMPAR synaptic localization by mechanical stimulation. In addition, mutations that prevent the ubiquitination of GLR-1 prevent the decrease in AMPAR localization observed in previously stimulated magi-1 mutants. Finally, we find that previously-stimulated animals later habituate to subsequent mechanostimulation more rapidly compared to animals initially reared without mechanical stimulation; MAGI-1L, GLR-1, and GLR-2 are required for this change in habituation kinetics. Our findings demonstrate that prior experience can cause long-term alterations in both behavioral plasticity and AMPAR localization at synapses in an intact animal, and indicate a new, direct role for MAGI/S-SCAM proteins in modulating AMPAR localization and function in the wake of variable sensory experience.     

The whole-body shortening reflex of the medicinal leech: motor pattern,sensory basis,and interneuronal pathways

The leech whole-body shortening reflex consists of a rapid contraction of the body elicited by a mechanical stimulus to the anterior of the animal. We used a variety of reduced preparations — semi-intact, body wall, and isolated nerve cord — to begin to elucidate the neural basis of this reflex in the medicinal leech Hirudo medicinalis. The motor pattern of the reflex involved an activation of excitatory motor neurons innervating dorsal and ventral longitudinal muscles (dorsal excitors and ventral excitors respectively), as well as the L cell, a motor neuron innervating both dorsal and ventral longitudinal muscles. The sensory input for the reflex was provided primarily by the T (touch) and P (pressure) types of identified mechanosensory neuron. The S cell network, a set of electrically-coupled interneurons which makes up a fast conducting pathway in the leech nerve cord, was active during shortening and accounted for the shortest-latency excitation of the L cells. Other, parallel, interneuronal pathways contributed to shortening as well. The whole-body shortening reflex was shown to be distinct from the previously described local shortening behavior of the leech in its sensory threshold, motor pattern, and (at least partially) in its interneuronal basis.Abbreviations conn connective - DE dorsal excitor motor neuron - DI dorsal inhibitor motor neuron - DP dorsal posterior nerve - DP:B1 dorsal posterior nerve branch 1 - DP:B2 dorsal posterior nerve branch 2 - MG midbody ganglion - VE ventral excitor motor neuron - VI ventral inhibitor motor neuron     

Configurational pattern discrimination responsible for dishabituation in common toads Bufo bufo (L.): Behavioral tests of the predictions of a neural model

Summary Recently, a neural model of visual pattern discrimination for stimulus-specific habituation was developed, based on previous behavioral studies which demonstrated that toads exhibit a dishabituation hierarchy for different worm-like stimuli. The model suggests that visual objects are represented by temporal coding and predicts that the dishabituation hierarchy changes when the stimulus/background contrast direction is reversed or the stimulus size is varied. The behavioral experiments reported in this paper were designed to test these predictions, (1) For a pair of stimuli from the contrast reversal prediction, the experimental results validated the theory. (2) For a pair of stimuli from the size reduction prediction, the experimental results failed to validate the theory. Further experiments concerning size effects suggest that configurai visual pattern discrimination in toads exhibits size invariance. (3) Inspired by the Groves-Thompson account of habituation, we found that dishabituation by a second stimulus has a separate process from habituation to a first stimulus. This paper serves as an example of a fruitful dialogue between experimentation and modeling, crucial for understanding brain functions.Abbreviations a-h worm-like stimulus patterns - AT anterior thalamus - ERF excitatory receptive field - IRF inhibitory receptive field - RF receptive field - R2 to R4 retinal ganglion cell types - vMP posterior ventromedial pallium     

Contribution of neurons to habituation to mechanical stimulation in Caenorhabditis elegans

In Caenorhabditis elegans, a light touch induces a locomotor response. Repeated touches, however, result in an attenuation of response, that is, habituation. Withdrawal responses elicited by anterior touch are controlled by anterior mechanosensory neurons (AVM and ALMs), and by four pairs of interneurons (AVA, AVB, AVD, and PVC) (Chalfie et al., 1985; White et al., 1986). To identify the neurons that participate in habituation, we ablated these neurons with a laser microbeam and investigated the resulting habituation of the operated animals. The animals lacking both left and right homologues AVDLR were habituated more rapidly than intact animals. We propose that chemical synapses at AVD play a critical role in the habituation of intact animals.     

Processing of mechanosensory information from gustatory receptors on a hind leg of the locust

Gustatory receptors (basiconic sensilla) on the legs of the desert locust, Schistocerca gregaria, are innervated by chemosensory afferents and by a mechanosensory afferent. We show, for the first time, that these mechanosensory afferents form an elaborate detector system with the following properties: 1) they have low threshold displacement angles that decrease with increasing stimulus frequency in the range 0.05–1 Hz, 2) they respond phasically to deflections of the receptor shaft and adapt rapidly to repetitive stimulation, 3) they encode the velocity of the stimulus in their spike frequency and have velocity thresholds lower than 1°/s, and 4) they are directionally sensitive, so that stimuli moving proximally towards the coxa elicit the greatest response.The mechanosensory afferents, but not the chemosensory afferents, make apparently monosynaptic connections with spiking local interneurones in a population with somata at the ventral midline of the metathoracic ganglion. They evoke excitatory synaptic potentials that can sum to produce spikes in the spiking local interneurones. Stimulation of the single mechanosensory afferent of a gustatory receptor can also give rise to long lasting depolarizations, or to bursts of excitatory postsynaptic potentials in the interneurones that can persist for several seconds after the afferent spikes. These interneurones are part of the local circuitry involved in the production of local movements of a leg. The mechanosensory afferents from gustatory receptors must, therefore, be considered as part of the complex array of exteroceptors that provide mechanosensory information to these local circuits for use in adjusting, or controlling locomotion.     

Processing of antennular input in the brain of the spiny lobster, Panulirus argus

Neurons in the olfactory deutocerebrum of the spiny lobster, Panulirus argus, were recorded intracellularly and filled with biocytin. Recorded neurons arborized in the olfactory lobe (OL), a glomerular neuropil innervated by olfactory and some presumptive mechanosensory antennular afferents. The neurons responded to chemosensory input from the lateral antennular flagellum bearing the olfactory sensilla but not the medial flagellum bearing many non-olfactory chemosensory sensilla. Many neurons received additional mechanosensory input. Thus the OL integrates specifically olfactory with mechanosensory input. OL neurons had multiglomerular arborizations restricted to one or two of the three horizontal layers of the columnar glomeruli. OL local interneurons comprised core neurons with tree-like neurites and terminals in the base of the glomeruli and rim neurons with neurites surrounding the OL and terminals in the cap/subcap. The somata of OL local interneurons lay in the medial soma cluster (100000 somata). OL projection neurons arborized in the base of the glomeruli and ascended via the olfactory glomerular tract to the lateral protocerebrum. A parallel projection pathway is constituted by projection neurons of the accessory lobe, a glomerular neuropil without afferent innervation but intimate links to the OL. The projection neuron somata constituted the lateral soma cluster (200000 somata).Abbreviations AC anterior cluster (cluster 6,7) - AL accessory lobe - aMC anterior subcluster of medial cluster (cluster 9) - A _lNv main antenna I (antennular) nerve - A _lNM antenna I (antennular) motor nerve - A _llNv main antenna II (antennal) nerve - CB central body - CL central layer of accessory lobe - DC deutocerebral commissure - DCN deutocerebral commissure neuropil - dDUMC dorsal subcluster of dorsal unpaired median cluster (cluster 17) - dMC dorsal subcluster of medial cluster (cluster 11) - dVPALC dorsal subcluster of ventral paired anterolateral cluster (cluster 8) G glomerulus - IDUMC lateral subcluster of dorsal unpaired median cluster (cluster 16) - LC lateral cluster (cluster 10) - LF lateral flagellum of antenna I (antennule) - LL lateral layer of accessory lobe - MF medial flagellum of antenna I (antennule) - ML medial layer of accessory lobe - MPN anterior and posterior median protocerebral neuropils - OGT olfactory globular tract - OGTN olfactory globular tract neuropil - OL olfactory lobe - OLALT olfactory lobe-accessory lobe tract - PB protocerebral bridge - pMC posterior subcluster of medial cluster (cluster 9) - PT protocerebral tract - TNv tegumentary nerve - VPMC ventral paired medial cluster (cluster 12) - VUMC ventral unpaired medial cluster (cluster 13) - vVPALC ventral subcluster of ventral paired anterolateral cluster (cluster 8) - ASW artificial sea water - M3 mixture 3 - PRO L-proline - TM TetraMarin extract     

Patterns and projections of crustacean cardioactive-peptide-immunoreactice neurones of the terminal ganglion of crayfish

Three distinct clusters of crustacean cardioactive-peptide-immunoreactive neurones occur in the terminal abdominal ganglion of the crayfish species Orconectes limosus, Astacus leptodactylus, Astacus astacus and Procambarus clarkii, as revealed by immunocytochemistry of whole-mount preparations and sections. They exhibit similar topology and projection patterns in all four studied species. An anterior ventral lateral and a posterior lateral cluster contain one small, strongly stained perikaryon and two large, less intensely stained perikarya, each showing contralateral projections. A posterior medial lateral cluster of up to six cells also contains these two types of perikarya. Whereas the small type perikarya belong to putative interneurones, the large type perikarya give rise to extensive neurohaemal plexuses in perineural sheaths of the third roots of the fifth abdominal ganglia, the connectives, the dorsal telson nerves, the ganglion itself, its roots and arteriolar supply. Thin fibres from these plexuses reach newly discovered putative neurohaemal areas around the hindgut and anus via the intestinal and the anal nerves, and directly innervate the phasic telson musculature. A comparison with earlier investigations of motoneurones and segmentation indicates that these three cell groups containing putative neurosecretory neurones may be members of at least three neuromeres in this ganglion. Crustacean cardioactive peptide released from these neurones may participate in the neurohumoral and modulatory control of different neuronal and muscle targets, thereby exceeding its previously established hindgut and heart excitatory effects.Abbreviations AG abdominal ganglion - adpl arteria dorsalis pleica - Ala arreria lateralis abdominalis - Asub arteria subneuralis - CCAP crustacean cardioactive peptide - CNS central nervous system - IR immunoreactive - LG lateral giant axon - LTr lateral tract - MDT medial dorsal tract - MG medial giant axon - M Tr medial tract - mcan musculus compressor ani - mfltp museulus flexor telsonos posterior - nan nervus ani (AG6 N5) - nant nervus anterior (AG6 N1, N2) - nia nervus intestinal anterior - nin nervus intestinalis (AG6 N7) - nip nervus intestinalis posterior - nteld nervus telsonos dorsalis (AG6 N6) - nielv nervus telsonos ventralis (AG6 N4) - nur nervus uropedalis (AG6 N3) - nven nervus ventralis (AG5 N3) - PIR peri-intestinal ring - PTF posterior telson flexor - VLT ventral lateral tract - VMT ventral medial tract - VNC ventral nerve cord - VIF ventral telson flexor - AVLC, PLC, PMLC anterior ventral lateral, posterior lateral, posterior medial lateral CCAP-immunoreactive cell cluster - A6AVC, A7AVC anterior ventral commissures - A7DCI dorsal commissure I - A7PVC posterior ventral commissure - A7SCII sensory commissure II - A7VCII, A7VCIII ventral commissures II and III of the sixth (A6) and seventh (A7) abdominal neuromer     

Regional distribution of glucose utilization in the telencephalon of toads in response to configurational visual stimuli: a14C-2DG study

Summary The regional glucose utilization in the telencephalon of toadsBufo bufo during stimulation with different visual key stimuli was quantitatively mapped by means of the¹⁴C-2DG autoradiographic method: (i) a 4×28 mm² worm-like stripe (W) eliciting prey catching responses, (ii) a 84×84 mm² square (S) releasing predator avoidance responses, and (iii) a 28×4 mm² antiwormlike stripe (A) eliciting no motor response.Various telencephalic structures changed¹⁴C- 2DG uptake statistical significantly during stimulation with the above visual objects in comparison with binocular enucleated animals (brain-to-brain comparison) and in comparison between both hemispheres in monocular animals (interhemispherical comparison): (1) The ventral two-thirds of the posterior half of the medial palliumdecreased ^14C-2DG uptake during W- and S-experiments, particularly in response to W. (2) In the posterior two-thirds of the lateral pallium,¹⁴C- 2DG uptake wasdecreased in response to the worm-, andincreased in response to the square (S) and antiworm stimuli (A). (3) The ventral striatumincreased uptake of¹⁴C-2DG during the animal's response to W- and S-stimuli significantly stronger than in the A-experiment. (4) The dorsal striatum also showed a significant change in¹⁴C-2DG uptake which, on a lower level, was not correlated with the type of stimulation experiment.Various prosencephalic structures are involved in circuitries related to attentional phenomena and the gating of prey catching and predator avoidance behavior. The different functions of these structures are discussed.Abbreviations A anterior dorsal thalamus - ACC nucleus ac-cumbens - APL amygdala, pars lateralis - APM amygdala, pars medialis - aLP anterior third of the lateral pallium - aMP anterior half of the medial pallium - B Bed nucleus of the palliai commissure - Ea entopeduncular nucleus, pars anterior - dMP dorsal medial pallium - dP dorsal pallium - dSTR dorsal striatum - La lateral thalamic nucleus, anterior division - Lpd lateral thalamic nucleus, postero-dorsal division - OT optic tectum - P posterior thalamic nucleus - pLP posterior two-thirds of the lateral pallium - PO preoptic area of the hypothalamus; - RET tegmental portion of the medial reticular formation - SEP medial (MS) and lateral (LS) septum - vMP ventral two-thirds of the medial pallium (MP) - vSTR ventral striatum     

Two types of plasticity in the tentacle withdrawal reflex of Helix aspersa are dissociated by tissue location and response measure

The tentacle withdrawal reflex of the terrestrial snail Helix aspersa was studied in vitro. The reflex is evoked by mechanical stimulation of the nose. Lesion experiments showed that 45% to 75% of the response amplitude is attributable to peripheral pathways alone. The central contribution increases with increasing stimulus intensity.Repeated stimulation produced pure habituation at low stimulus strengths, and habituation mixed with intrinsic sensitization (warm-up effect) at high stimulus strengths. The simultaneous occurrence of habituation and sensitization is consistent with the dual process theory of plasticity. Additional results differentiate the two processes. Habituation can occur without the CNS, whereas intrinsic sensitization requires the CNS. Also, the two processes are differentially effective in their influences on response amplitude and duration: habituation is more effective in determining response amplitude, while sensitization is more effective in determining response duration.Although the establishment of sensitization requires the CNS, 81% of the memory for intrinsic sensitization was localized to the periphery, by lesion experiments. Extrinsic sensitization, caused by stimulation of the medial lip nerve, had similar behavioural effects and a similar memory locus. Both types of sensitization appear to be caused by neuromuscular facilitation mediated by a central pathway.Abbreviations CNS central nervous system - PNS peripheral nervous system - S-R stimulus-response - TRM tentacle retractor muscle     

Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans

Dopamine has been implicated in the modulation of diverse forms of behavioral plasticity, including appetitive learning and addiction. An important challenge is to understand how dopamine's effects at the cellular level alter the properties of neural circuits to modify behavior. In the nematode C. elegans, dopamine modulates habituation of an escape reflex triggered by body touch. In the absence of food, animals habituate more rapidly than in the presence of food; this contextual information about food availability is provided by dopaminergic mechanosensory neurons that sense the presence of bacteria. We find that dopamine alters habituation kinetics by selectively modulating the touch responses of the anterior-body mechanoreceptors; this modulation involves a D1-like dopamine receptor, a Gq/PLC-beta signaling pathway, and calcium release within the touch neurons. Interestingly, the body touch mechanoreceptors can themselves excite the dopamine neurons, forming a positive feedback loop capable of integrating context and experience to modulate mechanosensory attention.     

Morphology of the Mechanosensory Lateral Line System in Elasmobranch Fishes: Ecological and Behavioral Considerations

The relationship between morphology of the mechanosensory lateral line system and behavior is essentially unknown in elasmobranch fishes. Gross anatomy and spatial distribution of different peripheral lateral line components were examined in several batoids (Raja eglanteria, Narcine brasiliensis, Gymnura micrura, and Dasyatis sabina) and a bonnethead shark, Sphyrna tiburo, and are interpreted to infer possible behavioral functions for superficial neuromasts, canals, and vesicles of Savi in these species. Narcine brasiliensis has canals on the dorsal surface with 1 pore per tubule branch, lacks a ventral canal system, and has 8–10 vesicles of Savi in bilateral rows on the dorsal rostrum and numerous vesicles ( = 65 ± 6 SD per side) on the ventral rostrum. Raja eglanteria has superficial neuromasts in bilateral rows along the dorsal body midline and tail, a pair anterior to each endolymphatic pore, and a row of 5–6 between the infraorbital canal and eye. Raja eglanteria also has dorsal canals with 1 pore per tubule branch, pored and non-pored canals on the ventral surface, and lacks a ventral subpleural loop. Gymnura micrura has a pored dorsal canal system with extensive branch patterns, a pored ventral hyomandibular canal, and non-pored canal sections around the mouth. Dasyatis sabina has more canal pores on the dorsal body surface, but more canal neuromasts and greater diameter canals on the ventral surface. Sphyrna tiburo has primarily pored canals on both the dorsal and ventral surfaces of the head, as well as the posterior lateral line canal along the lateral body surface. Based upon these morphological data, pored canals on the dorsal body and tail of elasmobranchs are best positioned to detect water movements across the body surface generated by currents, predators, conspecifics, or distortions in the animal's flow field while swimming. In addition, pored canals on the ventral surface likely also detect water movements generated by prey. Superficial neuromasts are protected from stimulation caused by forward swimming motion by their position at the base of papillar grooves, and may detect water flow produced by currents, prey, predators, or conspecifics. Ventral non-pored canals and vesicles of Savi, which are found in benthic batoids, likely function as tactile or vibration receptors that encode displacements of the skin surface caused by prey, the substrate, or conspecifics. This mechanotactile mechanism is supported by the presence of compliant canal walls, neuromasts that are enclosed in wide diameter canals, and the presence of hair cells in neuromasts that are polarized both parallel to and nearly perpendicular to the canal axis in D. sabina. The mechanotactile, schooling, and mechanosensory parallel processing hypotheses are proposed as future directions to address the relationships between morphology and physiology of the mechanosensory lateral line system and behavior in elasmobranch fishes.     

Escape trajectories of the rockpool prawn (Palaemon elegans) in response to visual and mechanosensory stimuli

Small crustaceans, such as the rockpool prawn Palaemon elegans Rathke, respond to the approach of predators by executing a version of the crustacean tail-flip response, known as the ‘jack-knife’. We used two types of stimulus to investigate the escape behaviour of P. elegans, specifically the escape trajectories taken by individual prawns. The first stimulus consisted of mechanosensory cues, while the second stimulus included visual and mechanosensory cues. Responses to the two stimulus types differed, with the combined cues from the second stimulus type resulting in escapes over longer distances, and with greater directionality, compared to those following purely mechanosensory stimulation. Altering the direction of approach of the ‘predator’ affected the proportion of escapes that were to the side opposite from the eliciting stimulus and strongly influenced escape trajectories. Such unpredictability in the escape direction of P. elegans may be an example of so-called ‘Protean’ behaviour.     

Primitive nervous systems: Peripheral habituation in decerebrate polyclad flatworms

The response to a vibration stimulus recorded from the cords of the ventral submuscular plexus of the polyclad flatworm, Notoplana acticola, consists of a burst of action potentials. The response can be abolished by the application of MgCl₂ to the sea water bathing the preparation. With repeated application of the stimulus, decreasing numbers of action potentials can be measured. This waning responsiveness can be dishabituated by applying a more intense vibration stimulus or with electrical shocks applied directly to the ventral nerve plexus. With electrical stimuli a number of shocks have to be applied before the response can be dishabituated. Changes in responsiveness can be measured simultaneously in a number of sites in the plexus even after the nerves between recording sites have been severed. With different interstimulus intervals the extent of habituation changes. As interstimulus intervals increase from 1 to 5 sec, there appears to be a decrease in responsiveness which recovers when interstimulus intervals become longer than 5 sec.     

Monoaminergic Orchestration of Motor Programs in a Complex C. elegans Behavior

Monoamines provide chemical codes of behavioral states. However, the neural mechanisms of monoaminergic orchestration of behavior are poorly understood. Touch elicits an escape response in Caenorhabditis elegans where the animal moves backward and turns to change its direction of locomotion. We show that the tyramine receptor SER-2 acts through a Gα_o pathway to inhibit neurotransmitter release from GABAergic motor neurons that synapse onto ventral body wall muscles. Extrasynaptic activation of SER-2 facilitates ventral body wall muscle contraction, contributing to the tight ventral turn that allows the animal to navigate away from a threatening stimulus. Tyramine temporally coordinates the different phases of the escape response through the synaptic activation of the fast-acting ionotropic receptor, LGC-55, and extrasynaptic activation of the slow-acting metabotropic receptor, SER-2. Our studies show, at the level of single cells, how a sensory input recruits the action of a monoamine to change neural circuit properties and orchestrate a compound motor sequence.     

Convergence of multisensory inputs in Xenopus tadpole tectum

The integration of multisensory information takes place in the optic tectum where visual and auditory/mechanosensory inputs converge and regulate motor outputs. The circuits that integrate multisensory information are poorly understood. In an effort to identify the basic components of a multisensory integrative circuit, we determined the projections of the mechanosensory input from the periphery to the optic tectum and compared their distribution to the retinotectal inputs in Xenopus laevis tadpoles using dye‐labeling methods. The peripheral ganglia of the lateral line system project to the ipsilateral hindbrain and the axons representing mechanosensory inputs along the anterior/posterior body axis are mapped along the ventrodorsal axis in the axon tract in the dorsal column of the hindbrain. Hindbrain neurons project axons to the contralateral optic tectum. The neurons from anterior and posterior hindbrain regions project axons to the dorsal and ventral tectum, respectively. While the retinotectal axons project to a superficial lamina in the tectal neuropil, the hindbrain axons project to a deep neuropil layer. Calcium imaging showed that multimodal inputs converge on tectal neurons. The layer‐specific projections of the hindbrain and retinal axons suggest a functional segregation of sensory inputs to proximal and distal tectal cell dendrites, respectively. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Interactions between two antagonistic reflexes in the nematode Caenorhabditis elegans

1. Antagonistic reflexes that use the same final common path cannot be activated simultaneously; as a consequence one reflex often inhibits the expression of the other. Results of experiments with two antagonistic reflexes in Caenorhabditis elegans showed that the reflex inhibition in this simple animal is the same as in more complex organisms. Thus C. elegans can serve as a model system for studying the neural mechanisms underlying these behavioral patterns. 2. In adult C. elegans tail-touch normally elicits forward movement, while tap normally elicits backward movement. When tail-touch is delivered 1 s before a tap, reversals to the tap are inhibited and the magnitude of any reversal that does occur is reduced. 3. The relative magnitude of the 2 stimuli, tail-touch and tap, affects the amount of inhibition observed. 4. The effectiveness of tail-touch as an inhibitory stimulus can be varied as a result of experience. Habituating the response to tail-touch decreased the inhibition of reversal to tap following a tail-touch. 4. The tail-touch induced inhibition of reversal to tap diminishes over an interval of at least 10 s; however, following the inhibition an enhancement of responding to tap is seen. 6. Inhibition of reversal to tap is present in worms of all stages of development including newly hatched worms.