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E R Kandel

Publications and source records attributed to E R Kandel.

At least 253 records · Page 14Linked to original sources
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↗
PubMed1979

Sensitization in Aplysia: restoration of transmission in synapses inactivated by long-term habituation.

Long-term habituation of a simple withdrawal reflex in Aplysia leads to an inactivation of synaptic transmission between identified sensory and gill motor neurons that persists for more than 3 weeks. A single sensitizing stimulus rapidly reactivates both the depressed behavioral response and the inactivated synaptic transmission. Thus sensitization, a simple competitive form of learning, provides a mechanism whereby changing environmental demands can rapidly override the long-term memory of habituation.

Animals↗
PubMed1979

Ultrastructure of the synapses of sensory neurons that mediate the gill-withdrawal reflex in Aplysia.

We have identified the processes of mechanoreceptor sensory neurons by intracellular injection of horseradish peroxidase in order to study the structure of synapses which exhibit profound, behaviourally-relevant plasticity. These synapses are located at small, varicose expansions along or at the end of the fine, microtubule-containing neurites, and they are crowded with vesicles some of which are associated with the varicosity membrane at regions of membrane specialization morphologically equivalent to active zones described in other species. These active zones occur between pre- and postsynaptic processes at two varieties of apposition: a conventional flat one, and a more elaborate indented one. At indented appositions, the presynaptic varicosity is invaginated by a thin (less than 0.25 micrometer diameter) spine of variable length. The active zones of indented synapses have approximately twice the vesicle frequency of flat synapses, suggesting that indented synapses are more effective. Sensory neuron terminals are relatively uniform in their structure, having similar concentrations of vesicles and numbers of active zones, and the majority of the processes postsynaptic to them are less than 0.5 micrometer in diameter. These regularities, and the presence of two strikingly-different types of synaptic apposition, flat and indented, should facilitate structural comparisons of neurons from naive and behaviourally-modified animals. The possible dynamic interconversion of indented and flat appositions at the synaptic terminals of sensory neurons and its behavioural relevance are discussed.

Animals↗
PubMed1979

Classical conditioning in Aplysia californica.

A form of aversive classical conditioning is described in which a chemosensory conditioned stimulus rapidly acquires the ability to modulate a defensive response (escape locomotion). Because Aplysia show both sensitization and classical conditioning, it is now possible to begin to examine the relationship between nonassociative and associative learning on behavioral and cellular levels.

Animals↗
PubMed1979

Quantitative analysis of relative contribution of central and peripheral neurons to gill-withdrawal reflex in Aplysia californica.

1. There is general agreement that the gill-withdrawal reflex elicited by weak tactile stimuli (less than 2 g to the siphon skin) is mediated almost entirely by the central nervous system (CNS) (13, 15, 18, 23). However, there was disagreement concerning the effects of moderate intensity (2--4 g) stimuli. Kupfermann et al. (18) found that the CNS mediates approximately 94% of the reflex elicited by moderate-intensity stimuli, whereas Peretz et al. (23) found that in this stimulus range, the amplitude of the reflex was, on average, unaltered when the CNS was removed. 2. To resolve this difference we first carried out pilot experiments in collaboration with B. Peretz, J. W. Jacklet, and K. Lukowiak using isolated mantle preparations, and then performed a systematic study using both the isolated mantle and intact animals. The main difference that seemed to account for the discrepancy in the results was the magnitude of the reflex response that was selected for study. Previous studies from this laboratory used a minimum-response criterion whereby only brisk and clearly observable responses of at least 35% maximum were examined. By contrast, Peretz et al. (23) examined all responses, even those that were extremely small. In addition, the two groups used different methods of stimulation so that stimulus intensities could not really be compared. 3. By comparing the effects of moderate-intensity stimuli in experiments with and without a response criterion in isolated mantle preparations, we found that when a minimal response-amplitude criterion is imposed the CNS mediates 90--95% of the gill-withdrawal reflex, whether it is elicited by the "tapper" stimulus used by Peretz et al. (23) or by the servo-controlled probe previously used in this laboratory. On the other hand, when no minimal response criterion is used and small responses are also examined, the response to the probe is still significantly reduced by 85% when the CNS is removed, whereas the reflex response to the tapper is more variable, sometimes increasing and other times decreasing with deganglionation. 4. We have also tested, in intact animals, the role of the CNS in mediating gill withdrawal. Water-jet stimuli were delivered to the siphon to elicit the reflex, as in previous behavioral studies. As was the case with probe stimulation in the isolated mantle preparation, in intact animals the CNS mediates 90% of the reflex evoked by moderate-intensity stimuli when a minimal response-amplitude criterion is imposed. 5. Our experiments indicate that, using response criteria and methods of stimulation, one can reliably study the reflex as predominantly mediated by the CNS.

Animals↗
PubMed1979

Cellular studies of peripheral neurons in siphon skin of Aplysia californica.

1. To account for the similarity in the kinetics of habituation between the central and peripheral components of siphon withdrawal, we have tested the idea (52) that each centrally located mechanoreceptor sensory neuron sends two branches to siphon motor neurons; one to centrally located siphon motor neurons and a collateral branch that remains in the periphery and innervates the peripheral siphon motor neurons. 2. We have found a group of peripheral siphon motor neurons and tested the connection onto these cells by central mechanoreceptors. In addition, we have defined by various electrophysiological and morphological criteria two general classes of peripheral neurons that lie along the course of the siphon nerve. 3. One class (type I) consists of only a single cell in each animal. This peripheral neuron typically has the largest cell body found lying along the siphon nerve and is the only peripheral nerve cell that appears white when viewed under epi-illumination. The type I neuron often has a highly regular firing pattern, which occurs in the absence of spontaneous synaptic input. The three-dimensional morphology of this neuron suggests a paucity of fine processes, most of which do not arborize and may terminate in the connective tissue sheath. Fine structural observations of the peripheral white cell have revealed the presence of large densecore granules. The peripheral type I neuron is similar in most of its electrophysiological and morphological properties to central neurons postulated to be neurosecretory. The peripheral white cell is, at present, the only peripheral neuron we can identify with certainty as a unique individual. 4. The second class (type II) of peripheral neurons are siphon motor neurons for the peripheral component of the siphon-withdrawal reflex. In contrast to the type I neurons, members of the second class of peripheral neurons possess smaller, more spherical cell bodies that have varying amounts of orange pigmentation and which give rise to a relatively well-developed and arborized dendritic tree. Type II neurons feature an irregular spontaneous firing pattern that is occasionally modulated by a rich spontaneous synaptic input. Peripheral siphon motor neurons have restricted motor fields that produce contraction of the mantle floor and the base of the siphon. Most of the type II neurons were found to be electrically coupled to one another. 5. The peripheral siphon motor neurons resemble the central siphon motor neurons in that they receive a collateral synapse from centrally located mechanoreceptor sensory neurons. This peripheral sensory-to-motor synapse exhibits the same kinetics of decrement as its central counterpart, both of which parallel behavioral habituation. 6. The rich mechanoreceptor input onto the relatively isolated dendritic trees of the peripheral siphon motor neurons provide a uniquely restricted neuropil to study the sensory-to-motor synapse. The peripheral motor neurons may, therefore, be a useful simple preparation for the cellular study of behavioral plasticity.

Animals↗
PubMed1978

Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica.

Long-term habituation training in Aplysia californica produces a profound depression in the efficacy of synaptic transmission between mechanoreceptor neurons and gill motor neurons. This depression persists for more than 3 weeks. Thus a critical synaptic site for plasticity underlying long-term habituation is the same as that for short-term habituation. For this simple form of learning, short- and long-term memory share a common locus and aspects of a common mechanism: synaptic depression.

Animals↗
PubMed1978

Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica.

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.

Action Potentials↗
PubMed1978

Stimulus-response relations and stability of mechanoreceptor and motor neurons mediating defensive gill-withdrawal reflex in Aplysia.

1. A weak or moderate-intensity tactile stimulus delivered to the siphon skin of Aplysia californica elicits a defensive reflex withdrawal of the gill and siphon into the mantle cavity. The reflex undergoes both short- and long-term habituation and sensitization and has, therefore, been used as a model system to examine various forms of learning. In this paper we describe studies of the response properties of the sensory and motor neurons of the reflex during repeated stimulation at rates that produce habituation. 2. The sensory neurons are slowly adapting mechanoreceptor cells whose frequency of discharge is a monotonic function of controlled-force punctate stimuli delivered to the skin. The majority of the stimulus-response relations could best be described by exponential functions. 3. We examined the stability of the sensory neuron responses in two ways; with punctate stimuli of varying intensity and with water jets of varying intensity. 4. With repeated punctate stimulation at rates which produce habituation in the intact animal the mechanoreceptor discharge showed no decrement. This stability was observed over a 10-fold range of intensities. 5. Weak or moderate intensity water-jet stimuli to the skin also gave stable responses but stronger stimuli caused the mechanoreceptor response to fatigue. 6. We examined the stability of the motor responses by using intracellular depolarizing current pulses to produce repetitive bursts of action potentials in gill motor neurons while monitoring the gill contractions with a strain gauge, photocell, or videotape recorder. The photocell and strain gauge were alternatively used in the same experiment. Gill contractions monitored with the photocell were stable, whereas those monitored by the strain gauge showed decrement. An independent measure of gill contraction, videotape recording, confirmed the results obtained with the photocell and showed that the gill contractions following repeated intracellular depolarization of the motor neurons were stable.

Action Potentials↗