Fruit flies can learn to associate an odor with an aversive stimulus, such as a shock. New findings indicate that disrupting the expression of N-methyl-D-aspartate (NMDA) receptors in flies impairs olfactory conditioning. The findings provide support for a critical role for NMDA receptors in associative learning.

Long-term potentiation of Aplysia sensorimotor synapses (apLTP) can be induced in Hebbian fashion by pairing brief tetanic stimulation of the sensory neuron with depolarization of the motor neuron. It has been proposed that Hebbian apLTP plays a significant role in classical conditioning of the defensive withdrawal reflex of Aplysia. However, as originally demonstrated, Hebbian apLTP is induced by simultaneous pairing of sensory neuron stimulation and motor neuron depolarization, whereas in the Aplysia classical conditioning paradigm the onset of the conditioned stimulus (CS) precedes the onset of the unconditioned stimulus (US) by 0.5 s. Therefore, if Hebbian apLTP does indeed mediate classical conditioning in Aplysia, temporally offset delivery of presynaptic stimulation and postsynaptic depolarization must be able to support apLTP. To ascertain whether temporally offset pre- and postsynaptic stimuli can support apLTP, we varied the interstimulus interval (ISI) between the onset of presynaptic tetanus and the onset of postsynaptic depolarization. In the first set of experiments we determined the amount of potentiation that results from varying the temporal interval between the onset of a single presynaptic tetanus and the onset of a single bout of postsynaptic depolarization. The ISI between the onset of the two stimuli ranged from 0.0 to 5.0 s. Significant apLTP was obtained with ISIs of 0.0 and 0.5 s. but the amount of potentiation was independent of the order in which the presynaptic and postsynaptic stimuli were delivered. Because classical conditioning of the withdrawal reflex in Aplysia is dependent on the temporal order of the CS and US, in a second set of experiments we compared the efficacy of forward and backward pairing of pre- and postsynaptic stimulation with the use of a conditioning-like protocol. Forward pairing and backward pairing (0.5-s ISI) yielded equal amounts of apLTP. These data raise questions for the hypothesis that Hebbian apLTP mediates classical conditioning of the withdrawal reflex in Aplysia. Our results indicate that Hebbian apLTP alone cannot fully account for classical conditioning in Aplysia. An additional cellular mechanism is required to explain the temporal specificity present in the behavioral results.

1. Activation of sensory neurons at 2 Hz for 15 min induces long-term depression (LTD) of isolated Aplysia sensorimotor synapses in cell culture. 2. Prior infusion of the Ca2+ chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) into the postsynaptic motor neuron blocks the induction of LTD, but not short-term synaptic depression. 3. Invertebrate central synapses possess the capacity for LTD. This form of long-term synaptic plasticity may play an important role in learning in Aplysia.

The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.

Noxious stimuli, such as electrical shocks to the animal's tail, enhance Aplysia's gill- and siphon-withdrawal reflex. Previous experimental work has indicated that this behavioral enhancement, known as dishabituation (if the reflex has been habituated) or sensitization (if it has not been habituated), might be mediated, at least in part, by the endogenous monoaminergic transmitter serotonin (5-HT). To assess 5-HT's role in dishabituation and sensitization of Aplysia withdrawal reflex, we treated Aplysia with the serotonergic neurotoxin 5,7- dihydroxytryptamine (5,7-DHT). We found that 5,7-DHT treatment significantly reduced the dishabituation of the withdrawal reflex produced by tail shock. Treatment with the neurotoxin also blocked the heterosynaptic facilitation of monosynaptic connections between siphon sensory neurons and their follower cells, which contributes to the behavioral enhancement. Analysis by high-performance liquid chromatography indicated that 5,7-DHT treatment significantly reduced 5- HT levels in the Aplysia CNS. Moreover, the neurotoxic effects of 5,7- DHT appeared to be relatively specific for serotonergic pathways. Thus, 5,7-DHT treatment did not disrupt the ability of nonserotonergic facilitatory interneurons, the L29 cells, to facilitate the connections of siphon sensory neurons. Also, 5,7-DHT reduced 5-HT-dependent, but not dopamine-dependent, histofluorescence in Aplysia central ganglia. Finally, 5,7-DHT does not reduce the levels of the facilitatory peptides SCPA and SCPB within the Aplysia CNS. Our results, together with those of Mackey et al. (1989), indicate that 5-HT plays a major role in mediating dishabituation and sensitization of Aplysia's withdrawal reflex.

The anterior insular gustatory neocortex (AIGN) has been implicated as a functional substrate of conditioned taste aversion (CTA) learning. Results of previous neuroanatomical and neurobehavioral experiments indicate that projections from gustatory-responsive neurons in the posterior ventromedial thalamic nuclei (parvicellular division; VPMpc) may provide relevant input to the AIGN during CTA learning. In rat, gustatory thalamocortical projections from VPMpc thalamus traverse the ventrolateral neostriatum (VLS) enroute to the AIGN. In these experiments, various neuroanatomical and neurobehavioral manipulations in the VLS were used to examine the contribution of presumed gustatory thalamocortical projections to CTA learning. These experiments demonstrate that projections from VPMpc thalamus to the AIGN are essential for normal CTA learning. Because both VPMpc thalamus and the AIGN each have been implicated as functional substrates of CTA learning, the present results suggest that the gustatory thalamocortical relay per se is necessary for normal taste-illness learning.

The amygdaloid complex is functionally implicated in conditioned taste aversion (CTA) learning. Results of previous neurobehavioral studies have provided equivocal evidence concerning the involvement of specific amygdaloid nuclei in CTA learning. The present study was conducted to examine the involvement of the central (CE), lateral (LA), and basolateral (BL) amygdaloid nuclei and the temporal neocortices (area 20) in CTA learning. To that end, distinct groups of rats received bilateral electrolytic lesion placements in the CE, LA, BL, or the temporal neocortices. Control animals received scalp and meningeal incisions only. Following recovery, animals were habituated to a restricted drinking schedule with distilled water. Animals then received CTA conditioning, with LiCl used both as the conditioned stimulus and as the unconditioned stimulus. Anterograde degeneration histologies were performed on all brain tissue to evaluate relations between CTA learning deficits and axonal pathology induced by lesion placements. Results of behavioral manipulations indicated that destruction of the CE, LA, or temporal neocortex impaired CTA acquisition, but damage induced to the basolateral amygdaloid nucleus did not. Anatomical observations indicated that degeneration of amygdalofugal and/or corticofugal projections to the convolutions of the olfactory tubercle (medial), subthalamic nucleus, and the parabrachial complex is correlated with CTA learning deficits. These results indicate that destruction of the dorsolateral amygdaloid nuclei and/or the temporal neocortices may produce CTA learning deficits by affecting olfactory, gustatory, and/or gastrointestinal processing in various portions of the forebrain.

Retrograde axonal transport of fluorescent dyes was used to demonstrate collateral projections from neurons of the pontine taste area (PTA) to gustatory-responsive areas of the posterior ventromedial thalamic nucleus (VPM), and to the gustatory neocortex (GN) of the rat. Dual-labeled PTA neurons were reliably observed following application of two different fluorescent dyes to the GN and to VPM thalamus. Dye injections into the GN and into thalamic regions surrounding the VPM nucleus, the bed nucleus of stria terminalis or the infralimbic neocortex, did not result in dual-labeled cells within the PTA. This finding suggests that gustatory information may be relayed simultaneously and specifically to VPM thalamus and to the GN via collateral axons of PTA neurons.

The functional relation between restricted damage to ventral primary somatosensory neocortex and the ability of rats to acquire conditioned taste aversion (CTA( was examined by a combination of behavioral and neurohistological techniques. Lesions confined exclusively to the established gustatory neocortex (GN) did not disrupt CTA acquisition, nor did lesions confined to suprarhinal cortical areas ventral to the GN. Lesions that encroached on dorsal prepiriform and insular cortices produced CTA acquisition deficits and damaged a large proportion of efferent projections to the prefrontal and precentral neocortex. In a second experiment, lesions of dorsal prepiriform and insular cortices did not modify taste preference-aversion threshold to any of the four taste modalities. It is concluded tha ventral somatosensory neocortical fields, including the established GN, do not mediate CTA acquisition and that rhinal cortices ventral and posterior to the GN are preferentially involved in associative learning for tastes and illness.

Horseradish peroxidase histochemistry was used to determine the course and extent of neuronal projections from the pontine taste area (PTA) to the gustatory neocortex (GN) in rat. Two distinct findings were encountered: (1) thalamocortical projections from posterior ventromedial thalamus to GN were confirmed, and (2) direct projections from cells located in the PTA to the GN were described. This novel anatomical finding supports previous suggestions that some gustatory information may be relayed to forebrain areas without making synaptic connection in the diencephalon.

The effects of ethyl alcohol on neuronal plasticity were examined using a model systems preparation of monosynaptic habituation: the lateral column to motoneuron pathway of the isolated frog spinal cord. Two fundamental effects of alcohol on this system were demonstrated. First, alcohol always depressed the ventral root responses to lateral column stimulation when stimulus intensity was held constant across conditions. This was accompanied by an increase in the amount of habituation produced as training progressed. Second, when stimulus intensity was increased in the alcohol condition so that responses were equated with pre-alcohol response amplitudes, the amount of habituation was markedly decreased. Results are discussed both in terms of proposed mechanisms of habituation and of possible pharmacological interactions with this simple example of response plasticity.

Intracellular recordings of spontaneous miniature synaptic potentials were made from motoneurons of the isolated spinal cord of the frog, as a function of habituation of the monosynaptic pathway originating with lateral column fibers. The frequency and amplitude of spontaneous miniature potentials were used to assess the possibility of several proposed mechanisms underlying habituation in this system. These studies provide clear evidence in eliminating the role of transmitter depletion, incomplete vesicle filling and receptor desensitization in the habituation process occurring within this vertebrate central nervous system.

Gaining insight into the mechanism of generation of goal-directed actions is important in understanding neural function. In this study we examined the role of the action potential (AP) in a single molluscan neuron (responsible for a defensive response) in an instrumental behavior. The intracellular electrical activity of two neurons was recorded simultaneously. One neuron was trained and the other served as a control neuron. When the trained neuron produced an AP in response to a conditioned stimulus (CS), the mollusc did not receive a painful stimulus. Delivery of the painful stimulus did not depend on the response of the control neuron. The number of AP's in a trained neuron, the AP latency and the threshold revealed a bell-shaped dependence on learning, whereas the response of the control neuron to a CS decreased during learning. It is apparently feasible to elaborate this type of instrumental reflex, so that the discharge of a single neuron may serve as an instrumental action for the entire animal. The membrane potential in a trained neuron varies significantly during instrumental learning, but the changes do not correspond to the dynamics of the instrumental reaction in the response to a CS. The control neuron exhibited weak but significant hyperpolarization during learning. The onset of the EPSP is determined by the timing of AP generation in presynaptic neurons. However, it changed in the trained neuron during the elaboration of an instrumental reflex. The alterations in the latency of EPSP's during learning were significant, but were not consistent with the time history of the conditioned response. Therefore, although the learning procedure was directed to only one neuron, the presynaptic neurons and neurons at the same neuronal level (command-like neurons of the same behavior) participated in the learning. The sign of the participation was not necessarily the same as that in the trained neuron.

The lumbar area of the spinal cords of adult frogs administered single injections of the drug 5,6-dihydroxytryptamine were treated with silver staining techniques for axonal and terminal degeneration. At all doses, maximal fiber degeneration occurred in the lateral columns of the spinal cord. The degeneration followed discrete patterns entering the spinal gray in bundles and terminating on somata and dendrites of interneurons and motoneurons. Fiber degeneration was also seen in the dorsal columns, particularly the dorsolateral zone and in the ventrolateral and ventromedial fiber tracts. Terminal degeneration was always heaviest in the ventral gray; fewer terminals were located in more dorsal areas of the central gray.

ArticlesHabituation of a monosynaptic response in vertebrate central nervous system: lateral column-motoneuron pathway in isolated frog spinal cordP. B. Farel, D. L. Glanzman, and R. F. ThompsonP. B. Farel, D. L. Glanzman, and R. F. ThompsonPublished Online:01 Nov 1973https://doi.org/10.1152/jn.1973.36.6.1117MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByThe development of serotonergic raphespinal projections in Xenopus laevisInternational Journal of Developmental Neuroscience, Vol. 4, No. 5Activation of brainstem serotoninergic pathways decreases homosynaptic depression of monosynaptic responses of frog spinal motoneuronsBrain Research, Vol. 280, No. 2The nictitating membrane response: An electrophysiological study of the abducens nerve and nucleus and the accessory abducens nucleus in rabbitBrain Research, Vol. 258, No. 2Habituation of the Hoffmann reflexBrain Research, Vol. 220, No. 2Disruption of vertebrate monosynaptic habituation by ethyl alcoholBrain Research, Vol. 212, No. 1The effects of hyposmolality on spinal cord activityLife Sciences, Vol. 28, No. 8Effects of changes in osmolality on spinal cord activityExperimental Neurology, Vol. 68, No. 3Alterations in spontaneous miniature potential activity during habituation of a vertebrate monosynaptic pathwayBrain Research, Vol. 189, No. 2Evidence against conduction failure as the mechanism underlying monosynaptic habituation in frog spinal cordBrain Research, Vol. 174, No. 2The bulbo-spinal indoleaminergic pathway in the frogBrain Research, Vol. 172, No. 2Inhibition of the monosynaptic responses in frog spinal motoneuronsNeuroscience, Vol. 4, No. 7Habituation of the nictitating membrane reflex response in the intact frogPhysiology & Behavior, Vol. 22, No. 6Effect of temperature on habituation of the LC-VR reflex of the frog spinal cordPhysiology & Behavior, Vol. 22, No. 4Reflex activity of regenerating frog spinal motoneuronsBrain Research, Vol. 158, No. 2Action of Mg2+ at low concentrations on the response to habituating stimuli and spontaneous activity of frog spinal cord motoneuronsBrain Research, Vol. 142, No. 1The efects of Ca2+ and Mg2+ on the habituating LCVR reflex of the frog spinal cordBrain Research, Vol. 139, No. 1The pharmacology of the amphibian spinal cordProgress in Neurobiology, Vol. 11, No. 1Brainstem reticular formation mechanisms subserving generalized seizures: Effects of convulsants and anticonvulsants on sensory-evoked responsesProgress in Neuro-Psychopharmacology, Vol. 2, No. 4Monosynaptic habituation in the vertebrate forebrain: The dentate gyrus examined in vitroBrain Research, Vol. 115, No. 3Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal sliceBrain Research, Vol. 110, No. 3Ultrastructural observations in the frog spinal cord in relation to the generation of primary afferent depolarizationNeuroscience Letters, Vol. 2, No. 3Criteria for distinguishing between monosynaptic and polysynaptic transmissionBrain Research, Vol. 105, No. 1The relation between monosynaptic spinal reflex amplitudes and some EEG alpha activity parametersElectroencephalography and Clinical Neurophysiology, Vol. 40, No. 3Sensitization and habituation of the plantar cushion reflex in catsBrain Research, Vol. 103, No. 2The effects of 5,6-dihydroxytryptamine in the amphibian spinal cord using silver staining techniquesBrain Research, Vol. 78, No. 2The effect of p-CPAand lesions of the dorsal raphe nucleus on habituation of the flexor withdrawal reflexBrain Research, Vol. 77, No. 3Dual processes control response habituation across a single synapseBrain Research, Vol. 72, No. 2Persistent increase in synaptic efficacy following a brief tetanus in isolated frog spinal cordBrain Research, Vol. 66, No. 1 More from this issue > Volume 36Issue 6November 1973Pages 1117-1130 Copyright & PermissionsCopyright © 1973 the American Physiological Societyhttps://doi.org/10.1152/jn.1973.36.6.1117PubMed4543415History Published online 1 November 1973 Published in print 1 November 1973 Metrics