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T J Carew

Publications and source records attributed to T J Carew.

At least 19 recordsLinked to original sources
PubMed1992

Delayed-onset sensitization emerges after dishabituation in developing Aplysia.

A recent study of the development of nonassociative learning in the siphon withdrawal reflex of Aplysia showed that dishabituation (facilitation of an habituated response) and sensitization (facilitation of a nonhabituated response) emerge according to different developmental timetables: dishabituation precedes sensitization by approximately 60 days (Rankin & Carew, 1988). Both forms of facilitation of the reflex were observed within 90 s of an electrical shock to the tail. However, more recent work by Marcus and colleagues (1988) in adult animals revealed that sensitization can have a delayed onset of 20-30 min after a strong tail shock. Since the developmental study of Rankin and Carew (1988) only tested the reflex for 10 min after tail shock, it is possible that sensitization was in fact present at earlier developmental stages, but was undetected. To examine this question, in the present study we utilized a longer (40-50 min) post-shock observation period to determine whether delayed-onset sensitization is exhibited in juvenile Aplysia, and if so, when it is expressed during development. In our first experiment, we found that Early Stage 12 juveniles (80-95 days after metamorphosis) showed significant delayed-onset sensitization 30-50 min after a strong tail shock. In a second experiment, we found that delayed-onset sensitization was absent in Stage 11 animals (20-70 days after metamorphosis). Thus delayed-onset sensitization emerges in Early Stage 12. The fact that the birthdate of delayed-onset sensitization is at least 30 days after that of dishabituation (Rankin & Carew, 1987, 1988) supports the hypothesis that these two forms of nonassociative learning may have at least partly different underlying mechanisms.

Animals↗
PubMed1991

Pharmacological dissociation of modulatory effects of serotonin in Aplysia sensory neurons.

In the mollusk Aplysia the neurotransmitter serotonin (5HT) has a fundamental modulatory role in several forms of learning and memory that involve an increase in the efficacy of synaptic transmission between tail sensory neurons (SNs) and motor neurons. The classical 5HT antagonist cyproheptadine (CYP) permits dissociation of three forms of serotonergic modulation in these SNs: (i) CYP reversibly blocks spike-broadening induced either by exogenous application of 5HT or by sensitizing stimulation of a tail nerve. (ii) CYP does not block 5HT-induced or tail input-induced increases in SN somatic excitability. (iii) Concomitant with its block of spike-broadening, CYP reversibly blocks 5HT-induced facilitation of synaptic transmission from SNs. These results suggest that endogenously released 5HT may act at different receptor subtypes that are coupled to different forms of neuromodulation in tail SNs of Aplysia.

Action Potentials↗
PubMed1991

An autoradiographic analysis of neurogenesis in juvenile Aplysia californica.

In developing Aplysia californica, a dramatic proliferation of new neurons occurs throughout the central nervous system (CNS) surprisingly late in juvenile development (Cash and Carew, 1989). In the present study, we investigated the source of these new neurons. Using tritiated thymidine autoradiography, we examined two different juvenile stages: stage 11 (before the large-scale proliferation) and stage 12 (at the peak of proliferation). Previous results implicated the body wall as a source for neurons in developing Aplysia (McAllister, Scheller, Kandel, and Axel, 1983; Jacob, 1984). Thus, we focused our attention on the body wall adjacent to a specific central ganglion, the abdominal ganglion. We found that in stage 11 there was uniform labelling of cells across the entire body wall. However, in stage 12 there was significantly more labelling in the body wall region immediately adjacent to the abdominal ganglion compared to flanking regions. Thus, at the time of neuronal proliferation, specific and highly localized regions of the body wall immediately opposite their target in the CNS show a significant increase in cell division. We also examined the distribution of labelled cells in the abdominal ganglion at survival times of 1 and 7 days after thymidine injection. In both stage 11 and stage 12, the fraction of labelled cells on the surface of the ganglion decreased over time, with a corresponding significant increase in the fraction observed on the inside. Our results support the hypothesis that specific regions of body wall are significantly up-regulated in juvenile Aplysia development, giving rise to widespread neuronal proliferation. These neurons then migrate from the body wall to their target ganglion, and from there continue migrating into the ganglion to achieve their final position.

Animals↗
PubMed1991

Development and modulation of endogenous bursting in identified neuron R15 of juvenile Aplysia.

Evidence from a variety of both vertebrate and invertebrate preparations has demonstrated that modulation of the intrinsic firing patterns of individual neurons can have a dramatic effect on the functional output of a neural circuit. Although the mechanisms underlying the production and modulation of intrinsic firing patterns have been extensively studied in adult nervous systems, relatively little is known about how these two features of intrinsically active neurons develop. To address these issues, we have examined the development of endogenous bursting and its modulation by neuropeptides in the identified cell R15 of juvenile Aplysia. Confirming Ohmori (1981), we found that the mature parabolic bursting pattern of R15 is absent in early juvenile stages and develops only gradually over the last stage of juvenile development. We have then analyzed the modulatory effects of extracts made from the neurosecretory bag cells of Aplysia on the immature firing pattern of juvenile R15 cells. In the adult, neuroactive peptides released from the bag cells are known to intensify bursting. In juveniles, we have found that bag cell extract (BCE) can induce bursting prematurely as well as intensify immature bursts, whereas control extracts have no effect on the firing pattern of R15. These results show that the ionic currents necessary for the generation of endogenous bursting in R15 are present and can be modulated before the normal developmental expression of the burst pattern.

Animals↗
PubMed1991

Identification of a reinforcement pathway necessary for operant conditioning of head waving in Aplysia californica.

The marine mollusc Aplysia californica exhibits a wide range of nonassociative and associative forms of learning. Recently, we found that the learning repertoire of Aplysia includes operant conditioning (Cook & Carew, 1986, 1989b). The behavior we examined is a naturally occurring, side-to-side head-waving response used by Aplysia in seeking food, obtaining a foothold, and egg laying. Aplysia can be operantly conditioned to reduce head-waving to one side of their body if such a response results in exposure to bright uniform-field illumination, which the animals find aversive. An essential step toward achieving a mechanistic understanding of operant conditioning is to identify and characterize the reinforcement pathway used during the learning. Toward this end, we wished to determine which of the peripheral visual pathways in Aplysia are critical for performance of the operant task. Previous experiments indicated that photic input from the optic and rhinophore nerves functionally inhibited motor neurons that participate in the operant response (head-waving), while photic input from the oral veil nerves excited these same motor neurons (Cook & Carew, 1989c). These findings suggested the hypothesis that one or both of these pathways could play an important role in mediating reinforcement during training. To explore this possibility we operantly trained animals that had received chronic bilateral transections of either the optic and rhinophore nerves or the oral veil nerves C1-C3 (in conjunction with transection of the optic and rhinophore nerves). We found that operant conditioning was not disrupted by ablation of input from the eyes and rhinophores. By contrast, ablation of input from the oral veil (together with that from the eyes and rhinophores) abolished operant conditioning. Thus, the oral veil nerves play a critical modulatory role in operant conditioning of head-waving. This observation further suggested that photic input from the oral veil is conveyed to the CNS via the oral veil nerves. In a final experiment we confirmed that stimulation of the oral veil with light evokes increased afferent activity in the oral veil nerves C1-C2. These results support the idea that the oral veil nerves contain processes that are critical components of the reinforcement pathway for operant conditioning of head-waving.

Afferent Pathways↗
PubMed1991

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.

Afferent Pathways↗
PubMed1991

A cellular analysis of inhibition in the siphon withdrawal reflex of Aplysia.

Recent behavioral experiments examining the siphon withdrawal reflex of Aplysia have revealed inhibitory effects of strong tail shock, a stimulus commonly used as an unconditioned stimulus in studies of associative and nonassociative learning in Aplysia. We utilized a reduced preparation to perform a cellular analysis of tail shock-induced inhibition in the siphon withdrawal reflex. First, we carried out behavioral studies that showed that the reduced preparation exhibits a siphon withdrawal reflex to water jet stimuli, and that tail shock produces inhibitory behavioral effects comparable to those in the intact animal: (1) strong shock produces transient inhibition of nonhabituated responses, and (2) a habituated response is facilitated by weak shock, but not by strong shock, suggesting that increasing tail shock intensity recruits the inhibitory process that competes with facilitation of habituated reflexes. Next, we carried out cellular studies that showed that the amplitude of the complex EPSP in siphon motor neurons elicited by water jet stimuli to the siphon also exhibits the inhibitory patterns produced by tail shock: (1) the nondecremented complex EPSP (a neural correlate of a nonhabituated siphon withdrawal reflex) is significantly inhibited 90 sec after strong tail shock and recovers to preshock levels 10 min later, and (2) the decremented complex EPSP (a neural correlate of a habituated reflex) is significantly facilitated by weak shock, but is not facilitated by strong shock. In addition to the complex EPSP, we simultaneously examined the monosynaptic connection between siphon sensory neurons and siphon motor neurons. The monosynaptic EPSP does not show the pattern of inhibitory modulation by tail shock exhibited by the siphon withdrawal reflex and the complex EPSP: (1) the nondecremented monosynaptic EPSP is not inhibited 90 sec after strong shock, but tends to be above preshock levels; and (2) the decremented monosynaptic EPSP is facilitated by weak as well as strong tail shock. Our results suggest that an important component of the inhibitory process triggered by strong tail shock is mediated by neural elements presynaptic to the siphon motor neurons. Because modulation of the monosynaptic connection between identified siphon sensory and siphon motor neurons does not parallel the tail shock-induced inhibitory patterns observed in the siphon withdrawal reflex and in the complex EPSP, other synaptic connections are likely to play an important role in mediating tail shock-induced inhibition in the siphon withdrawal reflex.

Animals↗
PubMed1991

Serotonin mimics tail shock in producing transient inhibition in the siphon withdrawal reflex of Aplysia.

Tail shock-induced modulation of the siphon withdrawal reflex of Aplysia has recently been shown to have a transient inhibitory component, as well as a facilitatory component. This transient behavioral inhibition is also seen in a reduced preparation in which a cellular reflection of the inhibitory process, tail shock-induced inhibition of complex EPSPs in siphon motor neurons, is observed. The biogenic amine serotonin (5-HT) is known to play a role in the facilitatory aspects of sensitization in Aplysia. The aim of this article was to examine whether 5-HT might also contribute to the inhibitory effects of tail shock in the siphon withdrawal reflex. To examine this question, we carried out two kinds of experiments. First, in the isolated abdominal ganglion, we recorded intracellularly from siphon motor neurons and examined the effects of 5-HT on (1) complex (polysynaptic) EPSPs, produced by siphon nerve stimulation, and, simultaneously, (2) monosynaptic EPSPs from siphon sensory neurons. We found that, paralleling the effects of tail shock in the reduced preparation, 5-HT produced transient inhibition of the complex EPSP; the monosynaptic EPSP was facilitated by 5-HT. Second, we examined the behavioral effects of 5-HT on siphon withdrawal in a reduced preparation. We found that 5-HT again paralleled tail shock by producing transient inhibition of the siphon withdrawal reflex. Our results suggest that, in addition to its well-established facilitatory role in reflex modulation in Aplysia, 5-HT might play an important inhibitory role, as well.

Animals↗
PubMed1990

Multiple forms of non-associative plasticity in Aplysia: a behavioural, cellular and pharmacological analysis.

A complete understanding of the cellular mechanisms underlying the formation of associations between stimuli, as occurs during classical conditioning, requires an understanding of the non-associative effects of the individual stimuli. The siphon withdrawal reflex of Aplysia exhibits both non-associative and associative learning when a tactile stimulus to the siphon serves as a conditioned stimulus, and tail shock serves as an unconditioned stimulus. In this chapter we describe experiments which examine the non-associative effects of tail shock at three different levels of analysis. At a behavioural level we found that the magnitude, and even the sign of reflex modulation induced by tail shock depended critically on three parameters: (i) the state of the reflex (habituated or non-habituated); (ii) the strength of the tail shock, and (iii) the time of testing after tail shock. Specifically, when non-habituated responses produced by water jet stimuli to the siphon were examined, tail shock produced transient inhibition 90 s later; facilitation of non-habituated responses (sensitization) only emerged after a considerable delay of 20-30 min. When habituated responses were examined, tail shock produced immediate facilitation (dishabituation); the amount of facilitation was inversely related to the strength of tail shock, with stronger shock producing no dishabituation. At a cellular level it was found that the complex excitatory postsynaptic potential (EPSP) in siphon motor neurons produced by water jet stimuli to the siphon provides a reliable cellular correlate of several of the non-associative effects of tail shock that we observe behaviourally. When non-decremented complex EPSPS were examined, strong tail shock produced transient inhibition at a test 90 s after shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The gastropod nervous system in metamorphosis.

Many gastropods, including the sea hare Aplysia californica, undergo metamorphosis in passing from the larval to the juvenile phases of their life cycle. During metamorphosis, the gastropod nervous system is affected by both progressive and regressive neuronal events. In addition to this metamorphic reorganization, the nervous system appears to be centrally involved in initiating metamorphosis. We propose that gastropods not only possess temporally distinct neuronal adaptations for the specific needs of the larval and juvenile phases, but also another transient neuronal adaptation specialized to subserve the metamorphic episode.

Animals↗
PubMed1989

A quantitative analysis of the development of the central nervous system in juvenile Aplysia californica.

The marine mollusc Aplysia californica has proved to be a useful preparation for analyzing the development of learning and memory on both behavioral and cellular levels. An important issue in this analysis concerns the anatomical substrate upon which learning is superimposed during development. As a first step in examining this question, in the present study we have determined the number of neurons in all the major central ganglia at each stage during juvenile development, a time when several forms of learning first emerge in Aplysia. We found that a large and highly nonlinear proliferation of neurons occurs during juvenile development, with the greatest increase in cell number occurring during a specific juvenile stage: Stage 12. The neuronal proliferation is system-wide, occurring in each of the central ganglia simultaneously, suggesting the action of a general developmental signal or trigger (perhaps a hormone). Accompanying the increase in neuron number in Stage 12 there is a large increase in neuropilar volume (150-fold), which significantly increases the opportunity for synaptic interactions late in juvenile development.

Animals↗
PubMed1989

Development assembly of learning in Aplysia.

Development can provide a powerful analytic approach for distinguishing and analysing specific behavioral, cellular and molecular processes as they emerge during ontogeny. Recently, such a developmental strategy has been used to investigate the functional assembly of different forms of non-associative learning (habituation, dishabituation and sensitization) in the marine mollusc Aplysia. This analysis has shown that different forms of learning, as well as their cellular analogs at central synapses, emerge according to very different developmental timetables. Subsequent behavioral studies in adult Aplysia showed that these same forms of learning were also clearly dissociable in the mature animal. These results, taken with earlier studies, suggest that a commonly held 'dual-process' view of non-associative learning, which attempts to account for all forms of non-associative learning as the interaction of only two processes (one decremental and one incremental) requires revision, and that a multi-process view, which includes the possibility of inhibitory as well as facilitatory interactions, is required to account adequately for all of the behavioral features of nonassociative learning.

Animals↗
PubMed1989

Operant conditioning of head-waving in Aplysia. I. Identified muscles involved in the operant response.

A basic goal in the neurosciences is to understand the cellular mechanisms underlying associative learning. The 2 major forms of associative learning are classical conditioning and operant conditioning. In recent years considerable progress has been made towards a cellular analysis of classical conditioning in a number of different preparations. In contrast, the cellular mechanisms underlying operant conditioning are poorly understood. Since the marine mollusc Aplysia has proved to be a powerful preparation for studying cellular and molecular mechanisms of a variety of forms of learning, including classical conditioning, we asked whether Aplysia might also be capable of exhibiting operant conditioning. In previous experiments we found that a naturally occurring behavior, the head-waving response of Aplysia, could be operantly conditioned (Cook and Carew, 1986). In the present paper we have carried out a quantitative analysis of the horizontal and vertical components of the head-waving response at the level of individual muscle groups. We have identified a discrete, bilateral band of neck muscles, the lateral columellar muscles (LCMs), whose electromyographic (EMG) activity is significantly correlated with the horizontal component of head-waving, the component modified by operant conditioning. Since head-waving is a complex behavioral response involving a variety of different muscle groups, using a restricted system such as the LCMs as an analog of the head-waving response will greatly facilitate a cellular analysis of operant conditioning in Aplysia.

Animals↗
PubMed1989

Operant conditioning of head-waving in Aplysia. II. Contingent modification of electromyographic activity in identified muscles.

Aplysia can readily exhibit operant conditioning of their head-waving response when bright light is used as aversive reinforcement (Cook and Carew, 1986). In the first paper of this series (Cook and Carew, 1989a), we showed that the electromyographic (EMG) activity of a discrete band of neck muscles, the lateral columellar muscles (LCMs) of Aplysia is significantly correlated with the component of head-waving (the horizontal component) that is modified during operant conditioning. In the present paper, we asked whether the EMG activity of the LCMs themselves could also be contingently modified, using the same procedures that produce operant conditioning of the behavioral response. Differential EMG from the LCMs was recorded in freely behaving animals with chronically implanted muscle cuff electrodes. Animals receiving aversive reinforcement (bright light) that was contingent upon specific patterns of LCM activity readily learned to alter their differential EMG output. Like operant conditioning of the head-waving response, this operant modification of LCM activity was rapidly acquired and was specific to the contingencies of reinforcement. These results show that a restricted group of muscles, the LCMs, exhibit the essential features of the head-waving system observed at the behavioral level: (1) their activity is significantly correlated with head-waving behavior, and (2) the LCMs are capable of operant modification of their output. Thus, this restricted response system provides a useful preparation for examining the neural mechanisms of operant conditioning of head-waving in Aplysia.

Animals↗
PubMed1989

Operant conditioning of head-waving in Aplysia. III. Cellular analysis of possible reinforcement pathways.

Operant conditioning of the head-waving response in Aplysia, as well as conditioning of the electrical activity of identified neck muscles, can be induced readily when bright light is used as aversive reinforcement (Cook and Carew, 1986, 1989b). A cellular analysis of this type of operant conditioning requires an understanding of the neural circuitry that underlies the reinforcement pathways involved in the conditioning. In the present paper we describe a cellular analysis of possible reinforcement pathways that mediate the aversive effects of bright light in the CNS of Aplysia. Using a semi-intact "split-body" preparation, we explored the effects of bright light on the operant response pathway by recording intracellularly from identified pedal neck and body wall motor neurons, which contribute to the operant response. In these experiments we identified 2 light-sensitive pathways. One pathway, from the eyes and rhinophores, mediated functional inhibition of light-induced excitation of pedal motor neurons. The other pathway, from the oral veil (cerebral ganglion nerves C1-C3) mediated significant excitation of the same motor cells. Randomly occurring blank trials ruled out the possibility that the light-induced effects were due to sampling bias. Finally, surgical isolation of the CNS from the periphery showed that none of the effects of light were due to direct illumination of central neurons. This identification of candidate reinforcement pathways will facilitate a cellular analysis of operant conditioning of head-waving in Aplysia.

Animals↗
PubMed1979

Motorneuronal control of locomotion in Aplysia.

We have carried out a combined behavioral and cellular analysis of escape locomotion in Aplysia. Using videotape recording we obtained a detailed description of the coordinated movements of the different regions of the foot and body during locomotion. Alternating waves of extension and longitudinal contraction begin at the head and propagate caudally through each pedal segment at a constant rate. Cobalt backfill of pedal nerves indicated that certain regions of the pedal ganglia were likely to contain motor neurons for the foot and body wall musculature. We examined these areas using intracellular techniques and identified three unique cells and three regional classes of neurons having clear motor effects on the foot and body wall. We also found that locomotion is driven by a central program. The basic locomotor pattern of the identified motor neurons and regional classes of motor neurons persists even after the circumesophageal ganglia have been isolated from the periphery. The motor neurons are not synaptically interconnected; patterned bursting during locomotor activity is produced by cyclic synaptic input. Because the locomotor system has large neurons favorable for cellular analysis and because locomotion is characterized by features of both stereotypy and flexibility, Aplysia promises to be useful for investigating the mechanisms underlying both the generation and modulation of a central program.

Animals↗