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1.
Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica 总被引：1，自引：0，他引：1
The defensive siphon and gill withdrawal reflex of Aplysia is a simple reflex mediated by a well-defined neural circuit. This reflex exhibits classical conditioning when a weak tactile stimulus to the siphon is used as a conditioned stimulus and a strong shock to the tail is used as an unconditioned stimulus. The siphon withdrawal component of this reflex can be differentially conditioned when stimuli applied to two different sites on the mantle skin (the mantle shelf and the siphon) are used as discriminative stimuli. The differential conditioning can be acquired in a single trial, is retained for more than 24 hours, and increases in strength with increased trials. Differential conditioning can also be produced within the field of innervation of a single cluster of sensory neurons (the LE cluster) since two separate sites on the siphon skin can serve as discriminative stimuli. The finding that two independent afferent inputs that activate a common set of interneurons and motor neurons can be differentially conditioned restricts the possible cellular loci involved in the associative learning. 相似文献
2.
Molecular biology of learning: modulation of transmitter release 总被引：82，自引：0，他引：82
Until recently, it has been impossible to approach learning with the techniques of cell biology. During the past several years, elementary forms of learning have been analyzed in higher invertebrates. Their nervous systems allow the experimental study of behavioral, neurophysiological, morphological, biochemical, and genetic components of the functional (plastic) changes underlying learning. In this review, we focus primarily on short-term sensitization of the gill and siphon reflex in the marine mollusk, Aplysia californica. Analyses of this form of learning provide direct evidence that protein phosphorylation dependent on cyclic adenosine monophosphate can modulate synaptic action. These studies also suggest how the molecular mechanisms for this short-term form of synaptic plasticity can be extended to explain both long-term memory and classical conditioning. 相似文献
3.
Learning to associate sensory cues with threats is critical for minimizing aversive experience. The ecological benefit of associative learning relies on accurate perception of predictive cues, but how aversive learning enhances perceptual acuity of sensory signals, particularly in humans, is unclear. We combined multivariate functional magnetic resonance imaging with olfactory psychophysics to show that initially indistinguishable odor enantiomers (mirror-image molecules) become discriminable after aversive conditioning, paralleling the spatial divergence of ensemble activity patterns in primary olfactory (piriform) cortex. Our findings indicate that aversive learning induces piriform plasticity with corresponding gains in odor enantiomer discrimination, underscoring the capacity of fear conditioning to update perceptual representation of predictive cues, over and above its well-recognized role in the acquisition of conditioned responses. That completely indiscriminable sensations can be transformed into discriminable percepts further accentuates the potency of associative learning to enhance sensory cue perception and support adaptive behavior. 相似文献
4.
Associative learning has been demonstrated in a reduced siphon, mantle, gill, and abdominal ganglion preparation of Aplysia. The preparations learned to respond to a previously neutral stimulus as a consequence of training in a classical conditioning paradigm. Backward conditioning, presentation of the conditioned stimulus alone, or presentation of the unconditioned stimulus at some random interval after presentation of the conditioned stimulus failed to produce conditioning. This model system can be used to study the neural mechanisms underlying associative learning. 相似文献
5.
Brembs B Lorenzetti FD Reyes FD Baxter DA Byrne JH 《Science (New York, N.Y.)》2002,296(5573):1706-1709
Operant conditioning is a form of associative learning through which an animal learns about the consequences of its behavior. Here, we report an appetitive operant conditioning procedure in Aplysia that induces long-term memory. Biophysical changes that accompanied the memory were found in an identified neuron (cell B51) that is considered critical for the expression of behavior that was rewarded. Similar cellular changes in B51 were produced by contingent reinforcement of B51 with dopamine in a single-cell analog of the operant procedure. These findings allow for the detailed analysis of the cellular and molecular processes underlying operant conditioning. 相似文献
6.
A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia 总被引：24，自引：0，他引：24
P G Montarolo P Goelet V F Castellucci J Morgan E R Kandel S Schacher 《Science (New York, N.Y.)》1986,234(4781):1249-1254
Both long-term and short-term sensitization of the gill and siphon withdrawal reflex in Aplysia involve facilitation of the monosynaptic connections between the sensory and motor neurons. To analyze the relationship between these two forms of synaptic facilitation at the cellular and molecular level, this monosynaptic sensorimotor component of the gill-withdrawal reflex of Aplysia can be reconstituted in dissociated cell culture. Whereas one brief application of 1 microM serotonin produced short-term facilitation in the sensorimotor connection that lasted minutes, five applications over 1.5 hours resulted in long-term facilitation that lasted more than 24 hours. Inhibitors of protein synthesis or RNA synthesis selectively blocked long-term facilitation, but not short-term facilitation, indicating that long-term facilitation requires the expression of gene products not essential for short-term facilitation. Moreover, the inhibitors only blocked long-term facilitation when given during the serotonin applications; the inhibitors did not block the facilitation when given either before or after serotonin application. These results parallel those for behavioral performance in vertebrates and indicate that the critical time window characteristic of the requirement for macromolecular synthesis in long-term heterosynaptic facilitation is not a property of complex circuitry, but an intrinsic characteristic of specific nerve cells and synaptic connections involved in the long-term storage of information. 相似文献
7.
Linden DJ 《Science (New York, N.Y.)》2003,301(5640):1682-1685
Neuroscientists have long sought to elucidate the molecular underpinnings of the memories needed to learn, for example, a motor task. In his Perspective, Linden discusses new work (Koekkoek et al.) suggesting that long-term depression in Purkinje cells mediated by protein kinase C signaling is responsible for motor memory in a task called associative eyelid conditioning. 相似文献
8.
cAMP evokes long-term facilitation in Aplysia sensory neurons that requires new protein synthesis 总被引：14，自引：0，他引：14
Behavioral sensitization leads to both short- and long-term enhancement of synaptic transmission between the sensory and motor neurons of the gill-withdrawal reflex in Aplysia. Serotonin (5-HT), a transmitter important for short-term sensitization, can evoke long-term enhancement of synaptic strength detected 1 day later. Because 5-HT mediates short-term facilitation through adenosine 3',5'-monophosphate (cAMP)-dependent protein phosphorylation, the role of cAMP in the long-term modulation of this identified synapse was examined. Like 5-HT, cAMP can also evoke long-term facilitation lasting 24 hours. Unlike the short-term change, the long-lasting change is blocked by anisomycin, a reversible inhibitor of protein synthesis, and therefore must involve the synthesis of gene products not required for the short-term change. 相似文献
9.
Imaging of memory-specific changes in the distribution of protein kinase C in the hippocampus 总被引：12，自引：0，他引：12
J L Olds M L Anderson D L McPhie L D Staten D L Alkon 《Science (New York, N.Y.)》1989,245(4920):866-869
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. 相似文献
10.
To examine the cellular mechanisms responsible for transition from a short-term to a long-term behavioral modification, a rapid training procedure was developed for producing long-term habituation of the defensive withdrawal of gill and siphon in Aplysia. Four ten-trial training sessions, with 1(1/2)-hour intersession intervals, produced habituation that was retained for more than 1 week. This 5-hour procedure could be applied to a test system in the isolated abdominal ganglion where the cellular changes accompanying the acquisition of long-term habituation can be examined. During acquisition, intracellular recordings were obtained from L7, a major gill and siphon motor neuron, and the pattern of stimulation used in the behavioral experiments was applied to an afferent nerve. Acquisition was associated with a progressive decrease in the complex excitatory synaptic potential produced in L7 by afferent nerve stimulation. When retention was tested 24 hours later, the synaptic decrement was still evident. Thus, a behaviorally meaningful stimulus sequence, consisting of only 40 patterned stimuli, leads to changes in synaptic effectiveness lasting one or more days in a neural pathway involved in short-term habituation of this reflex. 相似文献
11.
Tail shock produces transient presynaptic inhibition and longer lasting presynaptic facilitation of the siphon sensory neurons in Aplysia. The facilitation undergoes activity-dependent enhancement that is thought to contribute to classical conditioning of the gill- and siphon-withdrawal reflex. Inhibition of the sensory neurons has now also been shown to undergo activity-dependent enhancement when action potential activity in the sensory neurons is paired with inhibitory transmitter. This effect appears to involve an amplification of the same cellular mechanisms that are involved in normal presynaptic inhibition. These results suggest that activity-dependent enhancement may be a general type of associative cellular mechanism. 相似文献
12.
A fundamental problem in the cellular analysis of learning and memory is the identification of the neuronal substrates of long-term information storage and their relation to short-term cellular alterations. In this report, biophysical correlates of long-term sensitization of a simple withdrawal reflex in the mollusc Aplysia were examined. A voltage-clamp analysis of the sensory neurons that control the reflex, 24 hours after sensitization training, revealed a significant reduction in net outward current. The results indicate that one mechanism for the storage of long-term sensitization is the regulation of membrane currents that influence the characteristics of the action potential and the excitability of individual neurons. The results also provide insights into the relation between short- and long-term sensitization in that the biophysical loci involved in the storage of long-term sensitization appear similar to those involved in short-term sensitization. 相似文献
13.
Contributions of two types of calcium channels to synaptic transmission and plasticity 总被引：7，自引：0，他引：7
In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity. 相似文献
14.
Calcium-mediated reduction of ionic currents: a biophysical memory trace 总被引：25，自引：0，他引：25
D L Alkon 《Science (New York, N.Y.)》1984,226(4678):1037-1045
Learning behavior similar to vertebrate classical conditioning was demonstrated for the mollusc Hermissenda crassicornis. Postsynaptic membrane changes within well-defined neural systems that mediate the learning play a casual role in recording the learned association for later recall. Specific ionic currents in neural tissue undergo transformations lasting days after associative training with physiologic stimuli. During acquisition the intracellular calcium increases; this increase is accompanied by specific potassium current reduction that lasts for days after conditioning. The increase of calcium enhances calmodulin-dependent phosphorylation of proteins that either regulate or are part of ion channels. These currents and the conditions that precede their transformation occur in many types of vertebrate neurons, and hence this biophysical basis of Hermissenda learning could have relevance for species other than the gastropod studied. 相似文献
15.
Long-term potentiation in the motor cortex 总被引：4，自引：0，他引：4
Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills. 相似文献
16.
Stimulation of abducens nucleus supports classical conditioning of the nictitating membrane response
The acquisition and terminal performance of a classical conditioning group compared with a control group indicated that extension of the nictitating membrane elicited by direct electrical stimulation of the abducens nucleus was successfully conditioned to a previously neutral stimulus. The conditioning so obtained was associative and not due to such nonassociative factors as sensitization, pseudo-conditioning, or alteration in base-rate responding. 相似文献
17.
Associative conditioning of single sensory neurons suggests a cellular mechanism for learning 总被引：10，自引：0，他引：10
A cellular analog of associative learning has been demonstrated in individual sensory neurons of the tail withdrawal reflex of Aplysia. Sensory cells activated by intracellular current injection shortly before a sensitizing shock to the animal's tail display significantly more facilitation of their monosynaptic connections to a tail motor neuron than cells trained either with intracellular stimulation unpaired to tail shock or with tail shock alone. This associative effect is acquired rapidly and is expressed as a temporally specific amplification of heterosynaptic facilitation. The results suggest that activity-dependent neuromodulation may be a mechanism underlying associative information storage and point to aspects of subcellular processes that might be involved in the formation of neural associations. 相似文献
18.
Intracellular injection of cAMP induces a long-term reduction of neuronal K+ currents 总被引：5，自引：0，他引：5
Intracellular signals that trigger long-term (24-hour) changes in membrane currents in identified neurons of Aplysia have been examined in order to understand the cellular mechanisms underlying long-term sensitization. Adenosine 3',5'-monophosphate (cAMP) was directly injected into individual sensory neurons to mimic the effects of sensitization training at the single cell level. Potassium currents of these cells were reduced 24 hours after injection of cAMP; these currents were similar to those reduced 24 hours after behavioral sensitization. These results suggest that cAMP is part of the intracellular signal that induces long-term sensitization in Aplysia. 相似文献
19.
Facilitation of spindle-burst sleep by conditioning of electroencephalographic activity while awake 总被引：6，自引：0，他引：6
A slow-wave electroencephalographic rhythm recorded from the sensorimotor cortex of the waking cat has been correlated behaviorally with the suppression of movement. Facilitation of this rhythm through conditioning selectively enhances a similar pattern recorded during sleep, the familiar spindle burst. The training also produced longer epochs of undisturbed sleep. The specific neural mechanism manipulated during wakefulness appears to function also in sleep and to be involved with the regulation of phasic motor behavior. 相似文献
20.
J F Flood E L Bennett A E Orme M R Rosenzweig M E Jarvik 《Science (New York, N.Y.)》1978,199(4326):324-326
Mice were trained in a passive (foot shock)avoidance task. When administered after training, the stimulants caffeine or nicotine blocked amnesia for the task that had been produced by injections of the protein synthesis inhibitor anisomycin given prior to training. With foot shock at a higher intensity, anisomycin did not produce amnesia by itself, but the administration of the depressants chloral hydrate or sodium phenobarbital after training did cause amnesia. Stimulants and depressants did not have an appreciable influence on the overall degree of protein synthesis inhibition produced by anisomycin. The results support the hypothesis that arousal after training is an important factor in the conversion of short-term to long-term memory. 相似文献