Central localization of plasticity involved in appetitive conditioning in Lymnaea

Learning to associate a conditioned (CS) and unconditioned stimulus (US) results in changes in the processing of CS information. Here, we address directly the question whether chemical appetitive conditioning of Lymnaea feeding behavior involves changes in the peripheral and/or central processing of the CS by using extracellular recording techniques to monitor neuronal activity at two stages of the sensory processing pathway. Our data show that appetitive conditioning does not affect significantly the overall CS response of afferent nerves connecting chemosensory structures in the lips and tentacles to the central nervous system (CNS). In contrast, neuronal output from the cerebral ganglia, which represent the first central processing stage for chemosensory information, is enhanced significantly in response to the CS after appetitive conditioning. This demonstrates that chemical appetitive conditioning in Lymnaea affects the central, but not the peripheral processing of chemosensory information. It also identifies the cerebral ganglia of Lymnaea as an important site for neuronal plasticity and forms the basis for detailed cellular studies of neuronal plasticity.     

THE BASIS OF SUPERSTITIOUS BEHAVIOR: CHANCE CONTINGENCY,STIMULUS SUBSTITUTION,OR APPETITIVE BEHAVIOR?

This research examined three explanations for the "superstitious" behavior of pigeons under frequent fixed-time delivery of food: accidental response-reward contingency, stimulus substitution, and elicited species-typical appetitive behavior. The behavior observed in these studies consisted of occasional postfood locomotion away from the food hopper, and a predominant pattern of activity directed toward the hopper wall (wall-directed behavior), including approaching, stepping side to side, scratching with the feet, bumping with the breast, pendulum movements of the extended neck, and head bobbing, though not pecking. The consistency of these behavior patterns argued against explanation by accidental response contingencies, and the complexity of behavior was incompatible with the classic stimulus-substitution account. These studies also showed that: (1) response contingencies and prior stimulus experience can modify wall-directed behavior, but within definable limits; (2) pecking sometimes can be obtained in birds of specific strains, and by providing extended training; (3) placing the hopper in the floor at the center of a large chamber replaces wall-directed behavior with circling in a manner that resembles ground foraging for food. We conclude that superstitious behavior under periodic delivery of food probably develops from components of species-typical patterns of appetitive behavior related to feeding. These patterns are elicited by a combination of frequent food presentations and the supporting stimuli present in the environment.     

A single serotonergic modulatory cell can mediate reinforcement in the withdrawal network of the terrestrial snail

A cluster of 40 serotonergic cells in the rostral part of pedal ganglia of the terrestrial snail Helix lucorum was shown previously to participate in the modulation of withdrawal behavior and to be necessary during the acquisition of aversive withdrawal conditioning in intact snails. Local extracellular stimulation of the serotonergic cells paired with a test stimulus elicited a pairing-specific increase (the difference between paired and explicitly unpaired sessions was significant, p <.01) of synaptic responses to test stimulation in the premotor interneurons involved in withdrawal. This result suggested participation of serotonergic cells in mediating the reinforcement in the withdrawal network. Intracellular stimulation of only one identified Pd4 cell from the pedal group of serotonergic neurons paired with a test stimulus also significantly increased (the difference between paired and explicitly unpaired sessions was significant, p <.05) synaptic responses to paired nerve stimulation in same premotor interneurons involved in withdrawal. Morphological investigation of a cluster of pedal serotonergic neurons showed that only the Pd4 cell had branches in the parietal ganglia neuropile where the synapses of premotor withdrawal interneurons and of presynaptic neurons are located. The data suggest that a single serotonergic cell can mediate the reinforcement in the withdrawal network of the terrestrial snail. Patterns of responses of the Pd4 cells to tactile and chemical stimuli conform to the suggestion.     

A systems approach to the cellular analysis of associative learning in the pond snail Lymnaea

We show that appetitive and aversive conditioning can be analyzed at the cellular level in the well-described neural circuitries underlying rhythmic feeding and respiration in the pond snail, Lymnaea stagnalis. To relate electrical changes directly to behavior, the snails were first trained and the neural changes recorded at multiple sites in reduced preparations made from the same animals. Changes in neural activity following conditioning could be recorded at the level of motoneurons, central pattern generator interneurons and modulatory neurons. Of significant interest was recent work showing that neural correlates of long-term memory could be recorded in the feeding network following single-trial appetitive chemical conditioning. Available information on the synaptic connectivity and transmitter content of identified neurons within the Lymnaea circuits will allow further work on the synaptic and molecular mechanisms of learning and memory.     

情绪和社会行为的迷走神经活动基础

Porges基于自主神经进化观点提出的多迷走神经理论, 区分了无髓鞘迷走神经与髓鞘迷走神经的不同功能。认为对心脏等起调控作用的髓鞘迷走神经, 经由进化逐渐与调控头面部肌肉的脑神经之间产生了神经上的联系, 成为情绪和社会行为的神经基础。已有的相关实证研究表明, 髓鞘迷走神经与个体的情绪表达与调节、社会行为以及情绪与社会行为障碍密切相关。较低的迷走神经张力、较低的迷走抑制与较低的情绪调节能力相关; 迷走抑制较高的学前儿童有较少的行为问题以及较好的社交技能; 焦虑障碍的个体表现出较低的基线迷走张力以及较低的迷走抑制水平等。多迷走神经理论及其实证研究的结果, 对于推动情绪和社会行为的自主神经基础研究具有重要的意义。     

Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist

In a recently developed in vitro analog of appetitive classical conditioning of feeding in Aplysia, the unconditioned stimulus (US) was electrical stimulation of the esophageal nerve (En). This nerve is rich in dopamine (DA)-containing processes, which suggests that DA mediates reinforcement during appetitive conditioning. To test this possibility, methylergonovine was used to antagonize DA receptors. Methylergonovine (1 nM) blocked the pairing-specific increase in fictive feeding that is usually induced by in vitro classical conditioning. The present results and previous observation that methylergonovine also blocks the effects of contingent reinforcement in an in vitro analog of appetitive operant conditioning suggest that DA mediates reinforcement for appetitive associative conditioning of feeding in Aplysia.     

Identification of neuronal pathways mediating phototactic modulation of head-waving in Aplysia californica

The marine mollusc Aplysia californica exhibits a complex, rhythmic motor response, head-waving, in a variety of naturally occurring behavioral contexts. A cellular analysis of this behavior would be greatly facilitated by achieving stimulus control over the response. We have found that such stimulus control can be readily achieved by exposing a head-waving animal to a directional light source, which rapidly elicits a positive phototactic response: the animal either swings its head to face the light or biases its head waving toward the light source. Moreover, we have found that the neural pathways from the principal photoreceptive organs of Aplysia, the eyes and rhinophores, must be intact for the normal execution of this phototactic response: animals with chronic transection of the optic and rhinophore nerves show no phototactic behavior, whereas sham-operated animals continue to exhibit normal phototaxis.     

Primate head and body restraint without chronic skin openings or attachments to the animal

We developed a primate restraint system that requires no chronic skin openings or attachments to the animal. The restraining chair has a unique neck clasp; monkeys without chains and collars are easily trained to readily enter the chair and accept restraint with the neck and head held at a comfortable angle. A bite bar, in combination with contact on broad areas of the monkey’s brow and occiput, provides rigid head immobilization. In order to achieve contact with a broad area of the occipital bone, the muscles at the back of the animal’s head are surgically detached from the occiput and reattached to the underlying neck muscles. A strain-gauge, mounted on the head-holder and monitored by a laboratory computer, detects head movements of the monkey and permits the experimenter to teach the monkey to sit still during data acquisition. This system is well accepted by experienced monkeys and helps prevent the risks of infection posed by most earlier methods. Furthermore, the head and shoulders of the monkey are readily accessible for examination and for close positioning of test equipment.     

Two Modulatory Inputs Exert Reciprocal Reinforcing Effects on Synaptic Input of Premotor Interneurons for Withdrawal in Terrestrial Snails

A cluster of serotonergic cells in the rostral part of pedal ganglia of the terrestrial snail Helix lucorum was shown previously to participate in modulation of withdrawal behavior, and to be necessary for elaboration of aversive withdrawal conditioning in intact snails. In the present experiments local extracellular stimulation of the serotonergic cells elicited a pairing-specific increase (difference between paired and explicitly unpaired sessions was significant, P<0.01) of synaptic responses in the premotor interneurons involved in withdrawal to paired nerve stimulation. Intracellular stimulation of only one Pd4 cell from the pedal group of serotonergic neurons increased (P<0.05) synaptic responses to contingent test nerve stimulation significantly in the same premotor interneurons for 2–3 hr.     

In vitro analog of classical conditioning of feeding behavior in aplysia

The feeding behavior of Aplysia californica can be classically conditioned using tactile stimulation of the lips as a conditioned stimulus (CS) and food as an unconditioned stimulus (US). Moreover, several neural correlates of classical conditioning have been identified. The present study extended previous work by developing an in vitro analog of classical conditioning and by investigating pairing-specific changes in neuronal and synaptic properties. The preparation consisted of the isolated cerebral and buccal ganglia. Electrical stimulation of a lip nerve (AT4) and a branch of the esophageal nerve (En2) served as the CS and US, respectively. Three protocols were used: paired, unpaired, and US alone. Only the paired protocol produced a significant increase in CS-evoked fictive feeding. At the cellular level, classical conditioning enhanced the magnitude of the CS-evoked synaptic input to pattern-initiating neuron B31/32. In addition, paired training enhanced both the magnitude of the CS-evoked synaptic input and the CS-evoked spike activity in command-like neuron CBI-2. The in vitro analog of classical conditioning reproduced all of the cellular changes that previously were identified following behavioral conditioning and has led to the identification of several new learning-related neural changes. In addition, the pairing-specific enhancement of the CS response in CBI-2 indicates that some aspects of associative plasticity may occur at the level of the cerebral sensory neurons.     

Lifting weights in neonates: Developing visual control of reaching

To test whether newborn babies take account of external forces in moving their limbs, spontaneous arm-waving movements were measured while the baby lay supine with its head turned to one side. Free-hanging weights, attached to each wrist by strings passing over pulleys, pulled on the arms in the direction of the toes. The results showed the babies applied compensatory forces to keep the hand they faced moving in the same region. In contrast, the (invisible) contra-lateral hand was pulled down by the weights. In a second experiment, where the arms were occluded, both arms were pulled down, suggesting that sight of the arm was necessary in compensating for the weight. In a third, conclusive experiment the babies viewed the arm they were not facing on a small video-monitor and this time the babies kept the visible contra-lateral hand up despite the weights. The results challenge the general view that spontaneous arm movements of neonates are purposeless and either reflexive or due to spontaneous patterned efference to the muscles. Instead, the findings suggest that in waving their arms, neonates are developing visual control of reaching.     

Application testing of a new three-dimensional acceleration measuring system with wireless data transfer (WAS) for behavior analysis

A wireless acceleration measurement system was applied to free-moving cows and horses. Sensors were available as a collar and a flat box for measuring leg or trunk movements. Results were transmitted simultaneously by radio or stored in an 8-MB internal memory. As analytical procedures, frequency distributions with standard deviations, spectral analyses, and fractal analyses were applied. By means of the collar sensor, basic behavior patterns (standing, grazing, walking, ruminating, drinking, and hay uptake) could be identified in cows. Lameness could be detected in cows and horses by means of the leg sensor. The portion of basic and harmonic spectral components was reduced; the fractal dimension was reduced. The system can be used for the detection and analysis of even small movements of free-moving humans or animals over several hours. It is convenient for the analysis of basic behaviors, emotional reactions, or events causing flight or fright or for comparing different housing elements, such as floors or fences.     

Neonatal functioning and the sudden infant death syndrome

A male infant, diagnosed as a Sudden Infant Death Syndrome (SIDS) at 5 months, 3 weeks, had been extensively tested as a part of a larger sample in a longitudinal study. The longitudinal sample was comprised of 137 clinically normal neonates, born to intact upper middle-class families, living in a large metropolitan area. A neonatal assessment consisted of 5 hours of polygraphic recordings of heart and respiratory rate during sleep and waking cycles, and 1 hour of behavioral testing. At 3 months of age the infant was observed for 12 hours in the home. Retrospective analyses of these data suggested that: (a) neonatal respiratory behavior during sleep did not distinguish this infant from a sample of control infants; (b) the infant lacked strength in movements requiring the involvement of shoulder and neck muscles (head lift from a prone position); and (c) informal observations by skilled and experienced observers distinguished this infant from the sample of controls.     

TGF-β1 in Aplysia: Role in Long-Term Changes in the Excitability of Sensory Neurons and Distribution of TβR-II-Like Immunoreactivity

Exogenous recombinant human transforming growth factor β-1 (TGF-β1) induced long-term facilitation of Aplysia sensory-motor synapses. In addition, 5-HT-induced facilitation was blocked by application of a soluble fragment of the extracellular portion of the TGF-β1 type II receptor (TβR-II), which presumably acted by scavenging an endogenous TGF-β1-like molecule. Because TβR-II is essential for transmembrane signaling by TGF-β, we sought to determine whether Aplysia tissues contained TβR-II and specifically, whether neurons expressed the receptor. Western blot analysis of Aplysia tissue extracts demonstrated the presence of a TβR-II-immunoreactive protein in several tissue types. The expression and distribution of TβR-II-immunoreactive proteins in the central nervous system was examined by immunohistochemistry to elucidate sites that may be responsive to TGF-β1 and thus may play a role in synaptic plasticity. Sensory neurons in the ventral–caudal cluster of the pleural ganglion were immunoreactive for TβR-II, as well as many neurons in the pedal, abdominal, buccal, and cerebral ganglia. Sensory neurons cultured in isolation and cocultured sensory and motor neurons were also immunoreactive. TGF-β1 affected the biophysical properties of cultured sensory neurons, inducing an increase of excitability that persisted for at least 48 hr. Furthermore, exposure to TGF-β1 resulted in a reduction in the firing threshold of sensory neurons. These results provide further support for the hypothesis that TGF-β1 plays a role in long-term synaptic plasticity in Aplysia.     

Activation of MAPK is necessary for long-term memory consolidation following food-reward conditioning

Although an important role for the mitogen-activated protein kinase (MAPK) has been established for memory consolidation in a variety of learning paradigms, it is not known if this pathway is also involved in appetitive classical conditioning. We address this question by using a single-trial food-reward conditioning paradigm in the freshwater snail Lymnaea stagnalis. This learning paradigm induces protein synthesis-dependent long-term memory formation. Inhibition of MAPK phosphorylation blocked long-term memory consolidation without affecting the sensory and motor abilities of the snails. Thirty minutes after conditioning, levels of MAPK phosphorylation were increased in extracts from the buccal and cerebral ganglia. These ganglia are involved in the generation, modulation, and plasticity of the feeding behavior. We also detected an increase in levels of MAPK phosphorylation in the peripheral tissue around the mouth of the snails where chemoreceptors are located. Although an increase in MAPK phosphorylation was shown to be essential for food-reward conditioning, it was also detected in snails that were exposed to the conditioned stimulus (CS) or the unconditioned stimulus (US) alone, suggesting that phosphorylation of MAPK is necessary but not sufficient for learning to occur.     

Learned changes of respiratory pump rate in response to lowered pH in Aplysia

Respiratory pumping in the marine gastropod Aplysia is a well-characterized behavior controlled by identified neurons. The behavior is affected by stimuli such as change in ambient pH and shock. This study investigates learned changes in effects of these stimuli on rate of respiratory pumping movements. A sharp threshold exists for effects of environmental pH on respiratory pumping. Lowering the ambient pH from 7.8 to 7.0 does not affect the rate of respiratory pumping movements, but when pH is decreased further to 6.5 a large increase in pump rate is seen. Sensitizing stimuli, such as brief head shock and preexposure to pH 7.0, change the threshold so that respiratory pumping rate is increased in pH 7.0. Pairing exposure to pH 7.0 with head shock leads to pairing-specific amplification of the response in pH 7.0 alone. Pairing-specific consequences can be distinguished from sensitization only after an hour.     

Motivational control of sexual behavior in Aplysia fasciata: sequencing and modulation by sexual deprivation and by addition of partners

Variables similar to those affecting feeding behavior also modulate sexual behavior in Aplysia fasciata, indicating that mating is under motivational control. Motivated behaviors are often patterned into appetitive and consummatory components. Courtship, the appetitive phase of male sexual behavior, was temporally related to subsequent mating. Although many bouts of courtship failed to lead to mating, most incidents of mating were preceded by courtship. Motivation is also characterized by satiation after the goal of the behavior is achieved. We found an increase in likelihood to mate following a period of sexual isolation. Motivated behaviors are also modulated by environmental stimuli that induce arousal. Time spent mating was found to be a function of the number of potential mates accessible for mating. Number of A. fascinata participating in a mating group was also found to be a function of number of potential mates available.     

Stretch reflexes in the human masticatory muscles: a brief review and a new functional role

Stretch reflexes play a vital role in fine-tuning movements and in automatically maintaining posture. This article briefly reviews the operation of the stretch reflex in the human masticatory system. The conventional approach of stretching muscles in an open-loop manner has yielded much valuable information on the operation of this reflex. In particular, it has revealed that stretching the jaw-closing muscles evokes a reflex response with two major components. The short-latency reflex is favoured when stretches are brisk, but slower stretches evoke an additional long-latency component. In the hand muscles, the long-latency response is transcortical: in the masticatory muscles, it is not. In addition to its role in servo-control of muscle length during chewing, the stretch reflex in the jaw-closing muscles maintains the vertical position of the mandible during vigorous head movements such as those that occur during running, jumping, hopping and other vigorous whole-body movements in which the head moves briskly up and down. This is an interesting model system in which to investigate stretch reflexes with natural stimuli under unrestrained, physiological conditions.