Biomedical subjects

I Lederhendler

Publications and source records attributed to I Lederhendler.

8 recordsLinked to original sources

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

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↗

PubMed1988

Sequential modification of membrane currents with classical conditioning.

Pavlovian conditioning of the nudibranch mollusc Hermissenda crassicornis was previously shown to produce long-lasting reduction of two K+ currents measured across the Type B photoreceptor soma membrane (Alkon et al., 1982a; Alkon et al., 1985). Pavlovian conditioning of the rabbit was also shown to be followed by persistent K+ current reduction (Disterhoft et al., 1986). Here we report the first evidence that Ca2+ currents can also be modified by conditioning. The amplitude of the currents rather than their voltage-dependence remains reduced at least 1-2 d after conditioning (but not control procedures). Conditioning-induced changes of both K+ and Ca2+ currents increased as a function of training, the Ca2+ currents only changing substantially with greater than or equal to 250 trials. The later changes of the Ca2+ current may function to limit the magnitude of excitability increases due to associative learning.

Animals↗

PubMed1987

Effects of alpha 2-adrenergic agonists and antagonists on photoreceptor membrane currents.

Type B photoreceptors of the nudibranch mollusc Hermissenda crassicornis receive excitatory synaptic potentials (EPSPs) whose frequency is controlled by potential changes of a neighboring cell known as the S optic ganglion cell which is thought to be electrically coupled to the presynaptic source of these EPSPs, the E optic ganglion cell. The frequency of the EPSPs increases when a conditioned stimulus (light) is paired with an unconditioned stimulus (rotation) during acquisition of a Pavlovian conditioned response. The results of the present study are consistent with an adrenergic origin for these EPSPs. Noradrenergic agonists (greater than 100 microM), norepinephrine and clonidine, only slightly depolarize the type B cell but clearly prolong its depolarizing response to light. Serotonin, by contrast, causes hyperpolarization of the type B cell's resting potential as well as after a light step. Clonidine reduces voltage-dependent outward K+ currents (IA, an early current, ICa2+-K+, a late Ca2+-dependent current) that control the type B cell's excitability (and thus its light response and membrane potential). These effects of clonidine are reduced or blocked by the alpha 2-receptor antagonist, yohimbine (0.5 microM), but not the alpha 1-blocker, prazosin. The same yohimbine concentration also blocked depolarizing synaptic excitation of the type B cell in response to depolarization of a simultaneously impaled S optic ganglion cell. Histochemical techniques (both the glyoxylic acid method of de la Torre and Surgeon and the formaldehyde-induced fluorescence or Falck-Hillarp method) demonstrated the presence of a biogenic amine(s) within a single neuron in each optic ganglion as well as three or four cells within the vicinity of previously identified visual interneurons. No serotonergic neurons were found within the optic ganglion or in proximity to visual interneurons. A clonidine-like synaptic effect on type B cells, therefore, could amplify conditioning-specific changes of membrane currents by increasing type B depolarization and possibly, as well, by elevating intracellular second messengers.

Adrenergic alpha-Agonists↗

PubMed1986

The role of neurochemical modulation in learning.

Tsukahara creatively exploited the advantages of a "simple system" approach in a vertebrate context to gain cellular insights into the learning process. The molluscs Aplysia and Hermissenda have provided useful invertebrate examples of this approach. For classical conditioning of Hermissenda a temporal sequence of cellular transformations has been found to correspond to and to substantially account for a learning-specific behavioral transformation. For at least days after the conditioning a biophysical record persists: two voltage-dependent K+ currents, IA and ICa2+-K+, remain reduced in amplitude and at least IA shows an increased rate of inactivation. More recently, a similar biophysical record of associative memory has been identified in the mammalian brain (Disterhoft et al., 1986). Other experiments suggest that a synergistic interaction of C-kinase activation with Ca2+/CaM-kinase activation enhances and prolongs Ca2+-mediated K+ current reduction. The effects of alpha-receptor agonists to enhance depolarization of type B cells (a site of visual-vestibular convergence) and in turn acquisition of classical conditioning are in contrast to the effects of serotonin which can hyperpolarize and thereby reduce depolarization during the acquisition process. For both LTP and LTD, application of a neurotransmitter itself is not sufficient to produce long-lasting neural modification. In this respect, both the LTP and LTD models are more similar to the biochemical sequence implicated in Hermissenda conditioning than to the mechanism initiated by serotonin-like substances proposed for Aplysia sensitization.

Animals↗

PubMed1986

Implicating causal relations between cellular function and learning behavior.

Learning in the nudibranch mollusc Hermissenda shows many features of vertebrate associative conditioning. Pairings of light and rotation produce conditioned suppression of phototaxis, which is retained for days, shows savings, extinction, contingency sensitivity, and, recently, temporal specificity. In addition, specific features of the behavior have been shown to undergo classical Pavlovian conditioning. Extensive analysis of the neural networks mediating the flow of visual and graviceptive information have demonstrated convergent pathways at specific cellular loci. These cells are critically implicated for a primary role in the conditioned modifications of behavior. A variety of experimental approaches consistently support the proposal that reductions of specific K+ currents in the Type B photoreceptor soma play a causal role for several different behavioral expressions of the conditioning. In this article, we review several of these behaviors to show how the demonstrated close temporal correspondence of cellular and behavioral functions further implicates certain causal relations. For example, studies of the shadow withdrawal behavior of Hermissenda suggest a causal relation between the long-lasting depolarization of the Type B photoreceptor and the animal's reduced ability to turn towards the light at light/dark boundaries. Whereas the shadow response corresponded to cellular events at the end of a light step, responses to the onset of light or rotation were largely unexplored. By using a different approach, we identified behavioral responses during the first few seconds of stimulation with light and rotation. These responses, for which Pavlovian conditioning was demonstrated, correspond closely in time to known cellular correlates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Reduction of two voltage-dependent K+ currents mediates retention of a learned association.

A single identified neuron, the medial type B photoreceptor, was isolated by axotomy from the nervous systems of nudibranch molluscs (Hermissenda) which had been exposed to three different training experiences. Paired animals had been trained with repeated paired presentations of light and rotation and random animals with randomized light and rotation; naive animals had no training. A two-microelectrode voltage clamp of axotomized type B somata (separated from all synaptic interactions and impulse activity) was used to measure, with a blind procedure, three distinct ionic currents at least 24 h after the training experience. An early K+ current, IA, and a Ca2+-dependent K+ current, ICa2+-K+, but not a light-induced inward Na+ current, were significantly reduced for the paired as compared to the random and naive animals. The magnitude of ICa2+-K+ reduction was related (again measured blindly) to the degree of training-induced suppression of phototaxis (a measure of the learned behavior) for the paired animals. These data are consistent with previous observations indicating that changes of intrinsic type B membrane properties are an important means for encoding the acquisition and retention of Hermissenda associative learning.

Animals↗

PubMed1985

Input and output changes of an identified neural pathway are correlated with associative learning in Hermissenda.

The effect of associative training on an identified putative motoneuron (MN1) in an identified visual input-output neural pathway was studied in Hermissenda crassicornis. The increased impulse frequency of the MN1 cell in response to a light step (MN1-LR) was found to be smaller up to 54 hr after associative training with paired light and rotation stimuli. No change was found in animals which received these training stimuli randomly. The MN1 activity in darkness, namely, baseline impulse frequency, spike amplitude, input resistance, and resting potential, did not change after training. The MN1-LR was positively correlated on retention days with the behavioral latency of the animal to enter the illuminated area of a light intensity gradient. However, the input resistance of the type B photoreceptor was inversely correlated with this behavioral latency as well as with MN1-LR. These findings suggest that the reduction of MN1-LR may be caused by the biophysical changes which have been found in the type B photoreceptor membrane. Furthermore, these findings support several other studies which indicate that specific biophysical changes in the type B photoreceptor membrane play a causal role in the observed behavioral modifications after associative training in Hermissenda.

Animals↗