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E R Kandel

Publications and source records attributed to E R Kandel.

At least 271 records · Page 15Linked to original sources

Contribution of individual mechanoreceptor sensory neurons to defensive gill-withdrawal reflex in Aplysia.

1. To evaluate the contribution which mechanoreceptor sensory neurons make to the defensive gill-withdrawal reflex we developed an isolated reflex preparation. We then reduced this isolated reflex to a microcircuit (consisting of a single sensory cell and single motor cell) so as to causally relate the contribution of individual cells to the expression and plastic properties of the behavior. 2. Mechanoreceptor neurons make significant contributions to the amplitude and duration of the complex PSP in the motor neurons. A single spike in a sensory neuron produces an EPSP in the motor neuron which accounts for 7-36% of the complex EPSP produced by weak tactile stimulation of the skin. 3. More than 50% of the synaptic input to the gill motor neurons appears to be monosynaptic. Perfusing the ganglion with solutions of high divalent cations reduced the motor neurons' complex PSP by only 40%. 4. The population response of the mechanoreceptors to a point stimulus can be simulated by repetitively firing a single sensory neuron. Firing a single sensory cell discharges the motor neuron and produces a gill contraction similar to that produced by a natural stimulus. 5. Mechanoreceptors make monosynaptic connections onto gill motor neurons which decrement with repeated stimulation paralleling the decrement of the complex PSP to punctate tactile stimulation of the skin. 6. The results indicate that the known neural elements may quantitatively account for most of the expression of the behavior and its short-term habituation.

Animals↗

Short-term modulation of endogenous bursting rhythms by monosynaptic inhibition in Aplysia neurons: effects of contingent stimulation.

A presynaptic neuron fires a high-frequency train of spikes that produces long-lasting synaptic inhibition that modulates the bursting rhythm in a small population of endogenous bursting neurons in the left upper quadrant of the isolated abdominal ganglion of Aplysia. Single inputs decrease or increase the duration of the burst cycle as a function of the precise phase of the input (the phase response curve). Two phases of the burst cycle were used to analyze the effects of repeated contingent (phase-locked) stimulation. One contingency involved synaptic input early in the burst cycle that inhibited spikes and decreased the duration, whereas the other contingency involved input late in the cycle that increased the duration. Under both contingencies of stimulation, buildup and short-term persistence were found, however these cumulative effects were not dependent upon the phase of the burst cycle. The locus of the short-term plasticity that underlies the buildup and persistence is in the pacemaker properties of the postsynaptic cell rather than in the synapse. The plastic change appears to involve a nonspecific postinhibitory rebound that follows a single input and builds up with repetition. These results support the suggestion that endogenous rhythms of pacemaker cells can undergo plastic changes and can therefore serve as a means of short-term information storage in the nervous system. However, this neuronal circuit does not have the specificity required to mediate operant conditioning.

Action Potentials↗

Further identification of neurons in the abdominal ganglion of Aplysia using behavioral criteria.

This review is an updating of the paper by Frazier et at. 13 in which 30 individual cells and 8 cell clusters were identified in the abdominal ganglion of of Aplysia californica on the basis of morphological, physiological and pharmacological criteria. Since that time, a number of neurobiological studies have utilized the neurons of the abdominal ganglion for behavioral studies. Based on these new investigations, 32 additional cells and 2 additional cell clusters have been identified, bringing the total of identified cells in the ganglion to 62 individual cells and 10 cell clusters. Additional features of the previously identified cells have also emerged. Much of the new information concerns the role of identified cells in behavior. We have summarized the current list of identified cells in the abdominal ganglion emphasizing these behavioral features. We also review the known synaptic connections made by identified interneurons in the ganglion. Included are descriptions of 6 new interneurons that connect to other cells in the ganglion. A major conclusion from this survey is that behavioral criteria permit resolution between cells in identified cell clusters that could previously not be distinguished using other criteria.

Abdomen↗

Physiological and kinetic properties of cholinergic receptors activated by multiaction interneurons in buccal ganglia of Aplysia.

1. Neurons of Aplysia buccal ganglia contain three types of acetylcholine (ACh) receptors, each of which has been characterized by its sensitivity to inhibitors and kinetics of desensitization and by the properties of the conductance change it controls, including reversal potential, major ion, and functional consequence. The receptors are classified as depolarizing, slowly decrementing hyperpolarizing, and rapidly decrementing hyperpolarizing. Identified neurons are innervated by identified cholinergic multiaction interneurons; the form of the postsynaptic potential produced depends on the number and class of receptor found on each cell. 2. Interneuronal action potentials produce monosynaptic IPSPs by activating slowly decrementing hyperpolarizing receptors on seven cells in each ganglion. The IPSP reversal potential of 75 mV is shifted 42 mV in a depolarizing direction in Cl = free seawater. The ACh response has a reversal potential identical to that of the PSP; the PSP is blocked by 10(-4) g/ml curare but unaffected by hexamethonium. Interneuronal action potentials also produce monosynaptic EPSPs with a -14 mV extrapolated reversal potential by activating depolarizing receptors on one cell in each ganglion. This PSP is blocked by 10(-4) g/ml hexamethonium and mimicked by a Na-dependent ACh response. 3. Each interneuronal action potential also produces a diphasic depolarizing-hyperpolarizing synaptic potential in one cell in each ganglion as a result of released ACh acting on two classes of postsynaptic receptor on the same cell. One of these receptors is depolarizing; the other is a rapidly decrementing hyperpolarizing receptor. The two differ in their sensitivity to inhibitors, and the conductance changes they produce differ in their reversal potential, duration, and functional consequences. Both components can be mimicked by iontophoretic application of ACh. 4. Although the hyperpolarizing receptors on the inhibitory and diphasic follower cells have similar sensitivity to inhibitors and control similar conductance changes, they differ in their kinetics of desensitization. The hyperpolarizing receptor on the diphasic cell shows marked decrement to repeated presynaptic action potentials and to repeated iontophoretic application of ACh. This decrement is greater than that seen in either the hyperpolarizing receptor on the inhibitory follower cell or the depolarizing receptor on the dual follower cell. The shape of the PSP in the diphasic follower and its effect on firing of the cell are thus functions of both membrane potential and the degree of desensitization of the receptor. 5. Rate of desensitization is, therefore, an additional criterion for characterizing otherwise similar receptors for neurotransmitters.

Acetylcholine↗

Inking in Aplysia californica. III. Two different synaptic conductance mechanisms for triggering central program for inking.

1. In the previous two papers we described the motor elements which mediate all-or-none inking behavior in Aplysia (4) and the contribution of specific membrane properties of the ink-gland motor cells to the central program for inking (5). In the present paper we show that the central program for inking (a characteristic accelerating burst of action potentials in the motor cells) can be triggered in two different ways: 1) by means of a suprathreshold stimulus delivered to a single site on the animal; and 2) by means of two subthreshold stimuli closely spaced in time, delivered either to the same or to different sites on the animal. 2. The single suprathreshold stimulus triggers the central program primarily by means of a complex increased-conductance EPSP. The two subthreshold stimuli trigger the program by means of a complex decreased-conductance EPSP which is capable of augmenting subsequent afferent synaptic input. 3. The synaptic augmentation produced by the decreased-conductance EPSP is attributable to two properties of the EPSP: 1) it increases the input resistance of the ink-gland motor cells so that the synaptic current from afferent input onto the cells produces larger, more effective EPSP's; and 2) it increases the electrotonic coupling among the motor cells, thereby producing increased positive feedback among them. Thus, the decreased-conductance EPSP provides a novel mechanism for spatial and temporal summation.

Animals↗

Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia.

Sensitization is an elementary form of nonassociative learning, related to behavioral arousal, in which a strong stimulus facilitates a reflex response. Studies of the neural circuit of the gill-withdrawal reflex in the isolated abdominal ganglion on Aplysia indicate that short-term sensitization is due to presynaptic facilitation. The facilitation results in a sudden increase in the amount of neurotransmitter released by the sensory neurons at their synapses with motor neurons.

Animals↗

Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic AMP.

The neural changes accompanying sensitization of the gill-withdrawal reflex in Aplysia are associated with presynaptic facilitation at monosynaptic connections between sensory neurons and motor cells. To analyze the molecular mechanisms underlying the facilitation, the pharmacological actions of serotonin, octopamine, and dopamine were examined. Only serotonin enhanced synaptic transmission between the sensory and the motor neurons. A serotonin antagonist, cinanserin, reversibly blocked the synaptic facilitation. The action of serotonin may be mediated by adenosime 3',5'-monophosphate (cyclic AMP). Exposing the ganglion to dibutyryl cyclic AMP or injecting cyclic AMP into the cell body enhances the synaptic action of a sensory neuron. The mechanism of presynaptic facilitation, therefore, may include activation of one or more serotonergic neurons, which enhance the release of a neurotransmitter by increasing the intracellular concentration of cyclic AMP in the terminals of the sensory neurons.

Action Potentials↗

The morphology of identified neurons in the abdominal ganglion of Aplysia californica.

The morphology of identified neurons and of one multiaction interneuron (L10) of the abdominal ganglion of Aplysia has been studied using cobalt chloride, injected intracellularly. Cells with little synaptic input, R3-R14, had a relatively poorly developed dendritic tree, whereas the dendrite tree of cells L7 and L10, with extensive synaptic input, was highly complex. Cells L1-L6 and the RB cell cluster were found to have intermediate complexity of synaptic inputs and dendritic morphology. Within cell clusters, individual cells were often morphologically distinct. Identified cells have both invariant and variant axonal branches. Variant axons often project down other than their customary nerve trunks or are supernumerary. Three features of neuropil architecture were encountered. (1) When cells from the same cluster send their axons down the same nerve the axons often run in fascicles. (2) Although an identified cell's dendritic geometry varies from preparation to preparation, its dendrites always occupy approximately the same position in the neuropil. (3) The postsynaptic follower cells of L10 send their main axons through the axonal arborization of L10.

Animals↗

A radioautographic analysis in the light and electron microscope of identified Aplysia neurons and their processes after intrasomatic injection of L-(3H)fucose.

We have studied radioautographically the distribution and fate of 3H-glycoproteins within the single identified neurons L10 and R12 of Aplysia californica after intrasomatic pressure injection of [3H]fucose. Silver grains were localized to intracytoplasmic membranes in both cell body and axon 3 h after injection of the cholinergic neuron L10. Grains also appear at this time over presumptive synapses. In the cell body the Golgi apparatus was labeled, as were vesicles, multivesicular bodies, pigment granules, smooth endoplasmic reticulum, mitochondria and peroxisomes. The Golgi apparatus is the most intensely labelled organelle (relative specific activity 9,5). Over 50% of the silver grains are associated with the Golgi apparatus and with vesicles. In the axons, vesicles were labeled most intensely, having a relative specific activity of 40.4 (% silver grains/% area), an intensity 10 times that of similar appearing somatic vesicles, and 4.5--10 times that of other organelles (multivesicular bodies, mitochondria, smooth endoplasmic reticulum) in the axon. At least 32% of the silver grains are associated with vesicles. It appears that the biosynthetic machinery of these neurons is heavily involved in the production of vesicle membrane destined for transport along axons and to terminals. The preponderant labeling of vesicles in the axon parallels the rapid and perferential transport of glycoprotein components described by Ambron et al. and may indicate that specific glycoprotein molecules can be identified as components of these vesicles. After injection of the cholinergic neuron R2 transport of radioactivity was restricted to the axonal tree of the injected neuron. After injection of L10, one other neuron was invariably labeled. By varying the conditions of injection, as many as 5 other neuron cell bodies could be labeled. These are located in the position of cells known to be electrically coupled to L10, and they probably became labeled by transneuronal movement of fucose across electrotonic junctions. Since restriction of label to the injected neuron is easily determined in each experiment, this technique makes possible the identification of chemical and perhaps electrical synapses of identified cells with optimal preservation of fine structure.

Animals↗

Two functional effects of decreased conductance EPSP's: synaptic augmentation and increased electrotonic coupling.

Three electronically coupled motor neurons, which mediate inking behavior in Aplysia californica, receive both increased and decreased conductance excitatory postsynaptic potentials (EPSP's). The increased conductance EPSP's reduce electrical coupling among the cells, whereas the decreased conductance EPSP's increase electrical coupling. The decreased conductance EPSP's also augment the action of a previously ineffective sensory input and this augmentation is enhanced by the increase in electrical coupling. Both effects combine to trigger a stereotypic behavioral response.

Action Potentials↗

A quantal analysis of the synaptic depression underlying habituation of the gill-withdrawal reflex in Aplysia.

Habituation, one of the simplest behavioral paradigms for studying memory, has recently been examined on the cellular level in the gill-withdrawal reflex in the mollusc Aplysia and in the escape response in cray-fish. In both cases short-term habituation involved a decrease in excitatory synaptic transmission at the synapses between the sensory neurons and their central target cells. To analyze the mechanisms of the synaptic depression in Aplysia, we applied a quantal analysis to synaptic transmission between the sensory and motor neurons of the gill-withdrawal reflex. Our results indicate that short-term habituation results from a presynaptic mechanism: a decrease in the number of transmitter quanta released per impulse. The sensitivity of the postsynaptic receptor remains unaltered.

Action Potentials↗

Metamorphosis of Aplysia californica in laboratory culture.

To utilize the advantages offered by the large identified nerve cells of the marine mollusc Aplysia californica for cellular biological studies of development, we have devised simple techniques for growing this species in the laboratory in large number with a generation time as short as nineteen weeks. We have used the cultured animals to study the life cycle from fertilized egg to reproductive adult. The major developmental and behavioral changes occur at metamorphosis, when the larvae settle on the seaweed Laurencia pacifica and the locomotor and feeding behaviors are transformed into their adult forms. We have examined the timetable for the abandonment of larval behaviors and the emergence of adult ones and found that the transition from swimming to crawling occurs first and marks the onset of metamorphosis. The change from ciliary feeding to radular feeding occurs later and signals the end of metamorphosis. Other adult behaviors, such as the reflex responses and fixed-action patterns of the mantle organs, appear after metamorphosis.

Animals↗