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D L Alkon

Publications and source records attributed to D L Alkon.

At least 127 records · Page 7Linked to original sources
PubMed1990

Isolation of a G protein that is modified by learning and reduces potassium currents in Hermissenda.

In Hermissenda crassicornis conditioned to associate light and rotation, type B photoreceptor neurons exhibit pairing-specific decreases in the potassium currents IA and IK-Ca, which account for many of the behavioral changes elicited by associative conditioning. To determine which proteins are involved in storage of this memory, high-performance liquid chromatography was used to examine proteins from Hermissenda eyes. Conditioning-specific changes in four phosphoproteins were observed 24 hours after conditioning. One of these proteins, cp20, was purified to apparent homogeneity and found to be a G protein. When injected back into Hermissenda type B cells, cp20 reduced IK and IK-Ca in a manner indistinguishable from the reduction caused by conditioning, suggesting that this protein may play a crucial role in memory acquisition or retention.

Animals↗
PubMed1990

Sequential changes of potassium currents in Hermissenda type B photoreceptor during early stages of classical conditioning.

Classical conditioning of the marine snail Hermissenda can be produced in a single session of 50 pairings of light and rotation stimuli. Voltage clamp measurements of two outward K+ currents, IA and ICa2(+)-K+ were obtained from medial Type B photoreceptors that were isolated from the nervous system 1 day after animals were exposed to paired light and rotation stimuli or control procedures (Unpaired, or no exposure to light and rotation), ICa2(+)-K+ was found to be unchanged 18-30 h after 50 training trials. This result is consistent with a previous study where ICa2(+)-K+ was found to be unchanged after 50 light and rotation trials, although significantly reduced by 100 trials. In the present study 50 pairings of light and rotation produced a significant reduction in IA, suggesting an important role for this current in the earliest stages of classical conditioning.

Animals↗
PubMed1990

Pattern-recognition by an artificial network derived from biologic neuronal systems.

A novel artificial neural network, derived from neurobiological observations, is described and examples of its performance are presented. This DYnamically STable Associative Learning (DYSTAL) network associatively learns both correlations and anticorrelations, and can be configured to classify or restore patterns with only a change in the number of output units. DYSTAL exhibits some particularly desirable properties: computational effort scales linearly with the number of connections, i.e., it is O(N) in complexity; performance of the network is stable with respect to network parameters over wide ranges of their values and over the size of the input field; storage of a very large number of patterns is possible; patterns need not be orthogonal; network connections are not restricted to multi-layer feed-forward or any other specific structure; and, for a known set of deterministic input patterns, the network weights can be computed, a priori, in closed form. The network has been associatively trained to perform the XOR function as well as other classification tasks. The network has also been trained to restore patterns obscured by binary or analog noise. Neither global nor local feedback connections are required during learning; hence the network is particularly suitable for hardware (VLSI) implementation.

Animals↗
PubMed1990

Pavlovian conditioning of distinct components of Hermissenda's responses to rotation.

In two experiments with the nudibranch mollusk Hermissenda, distinct characteristics of conditioned and unconditioned responses to high-speed orbital rotation were examined. In Experiment 1, two principle unconditioned responses to rotation were identified, namely, reduced rate of locomotion and contraction of the foot. The magnitude of the foot contraction increased throughout a 20-s period of rotation, whereas locomotion was reduced immediately after the onset of the rotation and was maintained at this constant low rate throughout the stimulus presentation. These divergent response patterns suggest that the two responses emerge independently. In Experiment 2, a classical conditioning procedure was employed in which a light (CS) was paired with the rotation (US) employed in Experiment 1. In a subsequent test, it was found that the light had acquired the capability to evoke both foot contraction and decreased locomotion. Although the magnitude of these conditioned responses was reduced relative to the corresponding unconditioned response, the patterns of responding were virtually identical; that is, foot contraction developed gradually whereas locomotion decreased immediately. In contrast, animals that received unpaired presentations of the light and rotation, light alone, or no prior exposure to those stimuli exhibited foot extension in response to the light. These results illustrate a transfer of some of the response-evoking properties of the US to the CS as a result of conditioning, as well as the emergence of two independent conditioned responses. Moreover, these results suggest modulation of at least two distinct motor pathways as a function of learning.

Animals↗
PubMed1990

Early regulation of membrane excitability by ras oncogene proteins.

Two electrode voltage clamp conditions were used to study the early effects on ionic membrane channels of the intracellularly injected proto-oncogenic form of c-Ha-ras (c-ras) and its oncogenic counterpart v-Ha-ras (v-ras). These experiments were conducted on isolated somata of identified fully differentiated neurons of the sea snail Hermissenda. 20 min after c-ras, and 10 min after v-ras intracellular injections into type B medial photoreceptors of Hermissenda, the peak amplitude of two outward potassium currents (IA and IC), across the isolated Type B soma membrane begin to decrease. These two currents have been previously isolated by differences in activation and inactivation kinetics and their response to pharmacological blockers. c- or v-ras injections did not have any effect on a voltage-dependent inward calcium current. Reduction of IA preceded that of IC. Current reductions due to c-ras, but not to v-ras injection reversed spontaneously after 40 min. The voltage dependence of the steady state inactivation of IA shifted toward more negative potentials with ras injections. Ras-mediated cell transformations therefore, could involve, perhaps as initial events, prolonged modification of membrane currents.

Animals↗
PubMed1990

Acquisition of conditioned associations in Hermissenda: additive effects of contiguity and the forward interstimulus interval.

Conditioned suppression of photokinesis by the marine mollusc Hermissenda was examined in 3 experiments. In each experiment, groups of animals received light (the conditioned stimulus, CS) that was paired with high-speed orbital rotation (the unconditioned stimulus, UCS), light and rotation explicitly unpaired, or no exposure to these stimuli. Twenty-four hours after training, all animals were tested for suppression of photokinesis in the presence of the light. To establish the effectiveness of our conditioning procedure, in Experiment 1 individual groups of animals received either 50, 100, or 150 CS-UCS pairings. Fifty pairings resulted in a marginal suppression of photokinesis, whereas 100 and 150 pairings produced strong suppression. In Experiment 2, the delay between CS onset and UCS onset was varied between 1 and 10 s. The 10-s interstimulus interval (ISI) did not support conditioning, whereas 1-s and 2-s ISIs were effective. As predicted by the current understanding of Hermissenda's neural network, in Experiment 3 it was found that CS-UCS pairings in which the CS preceded the onset of the UCS and terminated with the offset of the UCS evoked stronger conditioned suppression than either a CS that preceded the UCS and terminated with its onset or a CS that was paired in simultaneous compound with the UCS. This result indicates that CS-UCS contiguity as well as the forward ISI act additively to establish the CS-UCS association. In none of the 3 experiments were any differences observed between groups that were untreated and that received the CS and UCS unpaired. In total, these experiments suggest strong similarities in the temporal characteristics of associative learning in Hermissenda and vertebrate species.

Animals↗
PubMed1990

Specific high molecular weight mRNAs induced by associative learning in Hermissenda.

Associative conditioning of Hermissenda crassicornis has been demonstrated to result in long-term changes in the potassium currents IA and ICa2(+)-K+ in photoreceptor neurons in the eye and to increase mRNA levels in the eye 2- to 3-fold. mRNA isolated from Hermissenda trained with paired light and rotation stimuli was labeled with [3H]acetic anhydride, while mRNA from naive animals or from animals subjected to random light and rotation stimuli was labeled with [14C]acetic anhydride. The labeled RNA was combined and separated by agarose gel electrophoresis. The overall size distribution of labeled mRNA was shifted to longer chain lengths in the paired group. In addition, the 3H/14C ratios were markedly increased for 21 distinct size bands, indicating increased mRNA of specific chain lengths in the paired group. Increases in the same size bands were also observed with mRNA labeled in vivo with 32Pi. This indicates that associative learning in Hermissenda results in a specific induction of a distinct set of at least 21 mRNAs, rather than in a generalized increase in synthesis of all mRNA, thus resembling in some respects a differentiation-like response.

Animals↗
PubMed1990

Contraction of neuronal branching volume: an anatomic correlate of Pavlovian conditioning.

Associative memory of the mollusc Hermissenda crassicornis, previously correlated with changes of specific K+ currents, protein phosphorylation, and increased synthesis of mRNA and specific proteins, is here shown to be accompanied by macroscopic alteration in the structure of a single identified neuron, the medial type B photoreceptor cell. Four to five days after training, terminal arborizations of B cells iontophoretically injected with Ni2+ ions and then treated with rubeanic acid were measured with charge-coupled device (CCD)-digitized pseudocolor images of optical sections under "blind" conditions. Boundary volumes enclosing medial-type B-cell arborizations from classically conditioned animals were unequivocally reduced compared with volumes for naive animals or those trained with unpaired stimuli. Branch volume magnitude was correlated with input resistance of the medial type B-cell soma. Such associative learning-induced structural changes may share function with "synapse elimination" described in developmental contexts.

Animals↗
PubMed1990

Discrimination learning alters the distribution of protein kinase C in the hippocampus of rats.

Protein kinase C (PKC), an enzyme that plays an essential role in eukaryotic cell regulation (Nishizuka, 1988; Huang et al., 1989), is critical to memory storage processes both in the marine snail Hermissenda crassicornis and in the rabbit (Alkon et al., 1988; Bank et al., 1988; Olds et al., 1989). Specifically, activation of PKC mimics neurobiological correlates of classical conditioning in both Hermissenda and the rabbit, and the distribution of the enzyme within the rabbit hippocampus changes after Pavlovian conditioning. Here, we report that the amount of PKC, as assayed by specific binding of 3H-phorbol-12,13-dibutyrate (3H-PDBU), decreased significantly within the hippocampal CA3 cell region in rats trained to solve a water maze task either by cognitive mapping or by visual discrimination strategies, but not in control rats. Furthermore, hippocampal lesions interfered with acquisition of both of these tasks. We interpret these findings to support the conclusion that distributional changes of PKC within the mammalian hippocampus play a crucial role in memory storage processes.

Animals↗
PubMed1990

Regulation of short-term associative memory by calcium-dependent protein kinase.

Neural and behavioral correlates of an associative memory in Hermissenda were examined during induction and/or formation of the memory. Hermissenda received either light (conditioned stimulus or CS) and rotation (unconditioned stimulus or US) paired (i.e., Pavlovian conditioning), light and rotation unpaired (pseudoconditioning), or no exposure to light and rotation. Following 9 pairings in a 6 min session, conditioned animals exhibited a contraction of the foot in response to a test CS presented 2 min after the last conditioning trial, whereas pseudoconditioned and untreated animals exhibited a foot extension to the same CS. In addition, both an associative and a nonassociative reduction in light-induced locomotion was observed. To examine neural correlates of this learning within minutes of acquisition, the isolated nervous system of the Hermissenda (containing the visual and vestibular organs) was trained with stimulus conditions identical to those used for the intact animal. Prior isolation and preparation of the nervous system permitted immediate intracellular recording following the final conditioning trial. Relative to pseudoconditioned and untreated animals, the B photoreceptors in conditioned nervous systems were found to have elevated input resistance (inversely related to K+ channel conductance and positively related to excitability) and exhibited increased steady-state depolarization in response to the light CS, as well as a prolonged depolarization after the CS offset. These neural correlates of the associative memory were attenuated if the protein kinase inhibitor H7 was present in the extracellular bath during conditioning, demonstrating in the reduced preparation that antagonism of protein kinase activity blocks the induction of membrane alterations of identified neurons that correlate with memory storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The interstimulus interval and classical conditioning in the marine snail Hermissenda crassicornis.

We examined the role of the interstimulus interval for the conditioned association between light and rotation stimuli in the marine snail Hermissenda. This interval between the conditioned stimulus (CS) and the unconditioned stimulus (US) is an important and widespread property of vertebrate associative learning. We demonstrated that with a forward CS-US delay of 1.0 s we were able to produce significant 24-h retention of an associative memory after 50 training trials. Other paired treatments providing intervals of 1.5 s, 0.5 s, simultaneous, and backward arrangements did not support retention at 24 h.

Animals↗
PubMed1989

Imaging of memory-specific changes in the distribution of protein kinase C in the hippocampus.

Activation of protein kinase C (PKC) can mimic the biophysical effects of associative learning on neurons. Furthermore, classical conditioning of the rabbit nictitating membrane (a form of associative learning) produces translocation of PKC activity from the cytosolic to the membrane compartments of the CA1 region of the hippocampus. Evidence is provided here for a significant change in the amount and distribution of PKC within the CA1 cell field of the rabbit hippocampus that is specific to learning. This change is seen at 1 day after learning as focal increments of [3H]phorbol-12,13-dibutyrate binding to PKC in computer-generated images produced from coronal autoradiographs of rabbit brain. In addition, 3 days after learning, the autoradiographs suggest a redistribution of PKC within CA1 from the cell soma to the dendrites.

Animals↗
PubMed1989

The nature of memory.

Memory, and its failings, are surely the most important factors in determining human behaviour. In humans and the higher animals the memory process is manifestly so complex as to defy direct experimental investigation. However, the snail Hermissenda crassicornis, with a nervous system many orders of magnitude simpler, has been shown to be capable of associative learning, and investigation of its cellular basis throws light on the mechanisms governing the memory process generally, and, more specifically, as now being revealed in the rabbit hippocampus and cerebellum.

Animals↗
PubMed1989

Hippocampal lesions impair memory of short-delay conditioned eye blink in rabbits.

Involvement of hippocampus in short-delay eye blink conditioning was reexamined during conditioned response (CR) consolidation. Rabbits received bilateral hippocampectomy, removal of overlying neocortex, or sham lesions and were trained with tone/puff pairings to early acquisition (consolidation) or well trained (overtraining); retention was tested. Two effects were observed: 1) Rabbits with hippocampal lesions showed less retention in the consolidation experiment than controls. Previous studies may not have found this because initial training was more complete. Overtrained hippocampal rabbits showed more retention, which agrees with this suggestion. 2) Hippocampectomized rabbits showed larger CR amplitudes in the overtraining experiment. The complementary roles of hippocampus in the consolidation process during early learning and in modulating the expression of the amplitude/time course of behavioral conditioned responses after associations are well learned are discussed.

Animals↗
PubMed1989

Classical conditioning reduces amplitude and duration of calcium-dependent afterhyperpolarization in rabbit hippocampal pyramidal cells.

1. The afterhyperpolarization (AHP) that follows action potentials was studied in CA1 hippocampal pyramidal cells from classically conditioned and control rabbits. Measurements of the AHP were obtained with intracellular recordings from CA1 cells within hippocampal slices. 2. The AHP of rabbit CA1 pyramidal cells was found to be accompanied by a conductance increase. The AHP was reduced by bath applications of the calcium channel blockers, cadmium and cobalt, by bath application of the cholinergic agonist, carbamylcholine chloride, and intracellular injection of the calcium chelator, ethylene glycol-bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). 3. The AHP was markedly reduced in cells from rabbits that were well-trained with the nictitating membrane conditioning procedure, as compared with cells from pseudoconditioned or naive control animals. The difference in AHP amplitudes between conditioned and control groups increased as the number of spikes elicited by the stimulation pulse increased from one to four. Both the duration (measured as the time constant of AHP decay) and amplitude of the AHP were reduced in cells from conditioned animals. 4. The reduced AHP in cells from conditioned animals remained reduced in a medium that contained 0.5 microM tetrodotoxin (TTX) and 5.0 mM tetraethylammonium chloride (TEA); the AHP following calcium spikes was measured under these conditions. Since this medium eliminated synaptic transmission elicited by Schaeffer collateral stimulation, the AHP reduction in pyramidal cells from conditioned animals was not due to a modification in synaptic properties. There were no significant differences in the mean voltage thresholds, amplitudes, or durations of calcium spikes between cells from animals in the three groups. Thus the AHP reduction appears to be due to a modification of a Ca2+ -dependent K+ conductance and was not due to a secondary effect of reductions in calcium conductances underlying the spike. 5. In medium containing TTX and TEA, the amount of injected current required to elicit a calcium spike (current threshold) was significantly greater in cells from conditioned animals than in cells from control animals. This increase in current threshold persisted in 4-aminopyridine (4-AP)-containing medium and so cannot be attributed entirely to conditioning-specific increases in the A-current. 6. The conditioning-specific AHP reduction resulted in increased excitability in cells from conditioned animals versus pseudoconditioned control animals. Cells from conditioned animals fired more spikes to trains of 100-ms depolarizing current pulses than did cells from controls.

4-Aminopyridine↗