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E R Kandel

Publications and source records attributed to E R Kandel.

At least 307 records · Page 17Linked to original sources
PubMed1969

Neuronal controls of a behavioral response mediated by the abdominal ganglion of Aplysia.

Tactile stimulation of the siphon and mantle shelf in Aplysia causes a characteristic withdrawal response of the external organs of the mantle cavity. A similar response also occurs spontaneously. Both responses are mediated by the abdominal ganglion and therefore provide an opportunity for correlating cellular functioning and behavior in a relatively simple and well-studied neuronal system. The withdrawal responses are controlled by five identified motor cells which receive two types of synaptic inputs. One set of excitatory connections, activated by tactile stimulation of the siphon and mantle shelf, mediates the defensive withdrawal reflex. A second set of connections is activated by a spontaneous burst of activity in a group of closely coupled interneurons which are excitatory to some of the motor cells and inhibitory to the others. This second set of connections mediates the spontaneous withdrawal response. These two inputs can therefore switch the same population of motor cells from a simple reflex to a more complex, internally organized response.

Abdomen↗
PubMed1969

Synaptic activation of an electrogenic sodium pump.

An identified molluscan interneuron mediates different cholinergic synaptic actions by increasing the conductance of its follower cells to different ions. We have now found that this interneuron also mediates a new class of synaptic actions which does not involve a conductance change but the activation of an electrogenic sodium pump. This synaptic action results in a prolonged inhibitory synaptic potential which is dependent on metabolism and is selectively blocked by cooling and ouabain. In cells which have this synaptic potential, part of the resting membrane potential is also maintained by an electrogenic sodium pump. The same transmitter, acetylcholine, can independently stimulate both a chloride ion conductance and a sodium pump mechanism in the same follower cell by acting on two different postsynaptic receptors.

Acetylcholine↗
PubMed1967

A direct synaptic connection mediating both excitation and inhibition.

Neurons have generally been thought to produce only one synaptic action on any particular cell which they innervate. An identified interneuron in the abdominal ganglion of Aplysia mediates both direct excitation and inhibition to an identified follower cell. At low firing rates the interneuron produces excitatory postsynaptic potentials; however at higher firing rates these gradually diminish in size and eventually invert to inhibitory postsynaptic potentials. Electrophysiological and pharmacological evidence indicates that the connection between these cells is monosynaptic, and that a single transmitter, acetylcholine, mediates both actions. These opposite synaptic responses appear to result from the transmitter's acting on two types of postsynaptic receptors having different thresholds for activation and different susceptibilities for desensitization.

Acetylcholine↗
PubMed1967

Opposite synaptic actions mediated by different branches of an identifiable interneuron in Aplysia.

Among the identifiable cells in the abdominal ganglion of Aplysia californica are five that generate bursting rhythms endogenous to the cells. In the four bursting cells of the left upper quadrant the rhythm is modulated by a unitary inhibitory postsynaptic potential; in the bursting cell of the right lower quadrant the rhythm is modulated by a unitary excitatory postsynaptic potential. Both the excitatory and inhibitory postsynaptic potentials are mediated by separate branches of a single interneuron. The pharmacological properties of the double action interneuron as well as those of the follower cells suggest that a single transmitter (acetylcholine) is involved in both the excitatory and the in-hibitory action of the interneuron.

Acetylcholine↗
PubMed1966

Input organization of two symmetrical giant cells in the snail brain.

1. The ventral surface of the snail brain contains two symmetrical giant cells which are readily identifiable in each preparation. These cells lie in the left and right metacerebrum, a cerebral integrative structure which makes afferent and efferent connexions with the periphery and with the infraoesophageal ganglia on each side by means of four ipsi- and four contralateral peripheral nerves and three ipsi- and three contralateral connectives.2. In order to examine the functional consequences of this anatomical symmetry single or double micro-electrodes, for intracellular recording and for direct stimulation, were placed in one or both of the ventral metacerebral giant cells.3. Responses from 6 ipsi- and 6 contralateral inputs were examined for orthodromic and antidromic components. The results of these experiments revealed that the output organization (the pathways of the three axonal branches of the giant cells) as well as the input organization were completely symmetrical in the two cells. The anatomical symmetry therefore seems to have been functionally preserved. Simultaneous recordings from both cells failed to reveal direct interconnexions, but did show that the cells do share in common the output of at least two interneurones.4. By recording from both cells it was also possible to demonstrate, for each of the symmetrical nerves and connectives, that laterality of an input was signalled by latency and by synaptic efficacy; the ipsilateral input produced EPSPs that were consistently more effective and of shorter latency than the contralateral ones.5. Pharmacological studies revealed that both cells fall into the category called D cells by Tauc & Gerschenfeld (1961); they responded with depolarization to iontophoretic injection of ACh and all excitatory synaptic inputs were blocked by d-tubocurarine.6. With none of the twelve afferent inputs was synaptic inhibition observed. The results support the notion that D cells do not receive inhibitory input.

Acetylcholine↗
PubMed1966

Anomalous rectification in the metacerebral giant cells and its consequences for synaptic transmission.

1. In the central neurones that have so far been examined the passive electrical properties of the extrasynaptic membrane has been shown to be relatively constant in the subthreshold range. Consequently, excitatory synaptic potentials produced by chemical transmission tend to vary in amplitude with changes in membrane potential, decreasing with depolarization and increasing with hyperpolarization.2. In the two symmetrical giant cells of the ventral metacerebrum of the snail, the EPSPs failed to show the expected alterations in amplitude with changes in membrane potential. Near the resting level the EPSP increased slightly with membrane depolarization and decreased slightly with hyperpolarization.3. These paradoxical results were not attributable to a change in transmitter release since similar results were obtained when ACh, the putative transmitter, was released iontophoretically on to the cell membrane by means of an extracellular pipette.4. Measurement of the current-voltage relation of the extrasynaptic membrane revealed two types of rectifying conductance changes. The first, an increase in conductance with depolarization, was turned on at a depolarization of about 15 mV. Its conductance change was similar to the delayed rectification familiar from studies of peripheral nerve and muscle. The second occurred on either side of the resting level, from about 15 mV hyperpolarization to about 10 mV depolarization, and manifested itself as a decrease in conductance with depolarization and an increase with hyperpolarization. By analogy to a similar phenomenon known to occur in skeletal muscle this second rectification has been termed anomalous rectification.5. The average resistance at 25 mV hyperpolarization was 2.3 x 10(6) Omega, while at 10 mV depolarization it was 2.1 x 10(7) Omega, yielding an average rectification ratio of 10 for the anomalous conductance change.6. The anomalous rectifying conductance seems to account for the paradoxical behaviour of the EPSP and ACh response to changes in membrane potential. Moreover, the finding that the sharpest change in the anomalous rectification curve occurred on either side of the resting level suggests that this rectification is functionally important as a postsynaptic determinant of synaptic efficacy. Several additional lines of evidence in support of this suggestion have been obtained.

Acetylcholine↗
PubMedDate not supplied

Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches.

Selected actions of neurotransmitters and hormones on ion channels in nerve and muscle cells are now thought to be mediated by cyclic AMP-dependent protein phosphorylation. Although the cyclic AMP-dependent protein kinase (cAMP-PK) affects the cellular properties of several neurones, its mode of action at the single-channel level has not been characterized. In addition, little is known about the identity or subcellular localization of the phosphoproteins that control channel activity and, in particular, whether the critical substrate proteins are cytoplasmic or membrane-associated. In Aplysia sensory neurones, serotonin produces a slow modulatory synaptic potential mediated by cAMP-PK that contributes to presynaptic facilitation and behavioural sensitization. Previously, we have found that serotonin acts on cell-attached membrane patches to produce prolonged all-or-none closures of a specific class of K+ channels (S channels) whose gating is weakly dependent on voltage and independent of intracellular calcium. We demonstrate here that in cell-free membrane patches from Aplysia sensory neurones, the purified catalytic subunit of cAMP-PK produces all-or-none closures of the S channel, simulating most (but not all) aspects of the action of serotonin on cell-attached patches. This result suggests that protein kinase acts on the internal surface of the membrane to phosphorylate either the channel itself or a membrane-associated protein that regulates channel activity.

Adenosine Triphosphate↗
PubMedDate not supplied

The long and the short of long-term memory--a molecular framework.

A single learning event initiates several memory processes with different time courses of retention. While short term memory involves covalent modification of pre-existing proteins, the finding that long-term memory requires the expression, during learning, of additional genes, makes it possible to analyse in molecular terms the induction and retention of long-term memory.

Animals↗
PubMedDate not supplied

Neuronal inhibition by the peptide FMRFamide involves opening of S K+ channels.

Neurotransmitters modulate the activity of ion channels through a variety of second messengers, including cyclic AMP, cyclic GMP and the products of phosphatidylinositol breakdown. Little is known about how different transmitters acting through different second-messenger systems interact within a cell to regulate single ion channels. We here describe the reciprocal actions of serotonin and the molluscan neuropeptide, FMRFamide, on individual K+ channels in Aplysia sensory neurons. In these cells, serotonin causes prolonged all-or-none closure of a class of background conductance K+ channels (the S channels) through cAMP-dependent protein phosphorylation. Using single-channel recording, we have found that FMRFamide produces two actions on the S channels; it increases the probability of opening of the S channels via a cAMP-independent second-messenger system and it reverses the closures of S channels produced by serotonin or cAMP.

Animals↗