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1.
An important body of evidence documents the differential expression of ion channels in brains, suggesting they are essential to endow particular brain structures with specific physiological properties. Because of their role in correlating inputs and outputs in neurons, modulation of voltage-dependent ion channels (VDICs) can profoundly change neuronal network dynamics and performance, and may represent a fundamental mechanism for behavioral plasticity, one that has received less attention in learning and memory studies. Revisiting three paradigmatic mutations altering olfactory learning and memory in Drosophila (dunce, leonardo, amnesiac) a link was established between each mutation and the operation of VDICs in Kenyon cells, the intrinsic neurons of the mushroom bodies (MBs). In Drosophila, MBs are essential to the emergence of olfactory associative learning and retention. Abnormal ion channel operation might underlie failures in neuronal physiology, and be crucial to understand the abnormal associative learning and retention phenotypes the mutants display. We also discuss the only case in which a mutation in an ion channel gene (shaker) has been directly linked to olfactory learning deficits. We analyze such evidence in light of recent discoveries indicating an unusual ion current profile in shaker mutant MB intrinsic neurons. We anticipate that further studies of acquisition and retention mutants will further confirm a link between such mutations and malfunction of specific ion channel mechanisms in brain structures implicated in learning and memory. 相似文献
2.
Mushroom body ablation impairs short-term memory and long-term memory of courtship conditioning in Drosophila melanogaster 总被引:1,自引:0,他引:1
McBride SM Giuliani G Choi C Krause P Correale D Watson K Baker G Siwicki KK 《Neuron》1999,24(4):967-977
We have evaluated the role of the Drosophila mushroom bodies (MBs) in courtship conditioning, in which experience with mated females causes males to reduce their courtship toward virgins (Siegel and Hall, 1979). Whereas previous studies indicated that MB ablation abolished learning in an olfactory conditioning paradigm (deBelle and Heisenberg, 1994), MB-ablated males were able to learn in the courtship paradigm. They resumed courting at naive levels within 30 min after training, however, while the courtship of control males remained depressed 1 hr after training. We also describe a novel courtship conditioning paradigm that established long-term memory, lasting 9 days. In MB-ablated males, memory dissipated completely within 1 day. Our results indicate that the MBs are not required for learning and immediate recall of courtship conditioning but are required for consolidation of short-term and long-term associative memories. 相似文献
3.
Since the discovery of adult neurogenesis, a major issue is the role of newborn neurons and the function-dependent regulation of adult neurogenesis. We decided to use an animal model with a relatively simple brain to address these questions. In the adult cricket brain as in mammals, new neurons are produced throughout life. This neurogenesis occurs in the main integrative centers of the insect brain, the mushroom bodies (MBs), where the neuroblasts responsible for their formation persist after the imaginal molt. The rate of production of new neurons is controlled not only by internal cues such as morphogenetic hormones but also by external environmental cues. Adult crickets reared in an enriched sensory environment experienced an increase in neuroblast proliferation as compared with crickets reared in an impoverished environment. In addition, unilateral sensory deprivation led to reduced neurogenesis in the MB ipsilateral to the lesion. In search of a functional role for the new cells, we specifically ablated MB neuroblasts in young adults using brain-focused gamma ray irradiation. We developed a learning paradigm adapted to the cricket, which we call the "escape paradigm." Using this operant associative learning test, we showed that crickets lacking neurogenesis exhibited delayed learning and reduced memory retention of the task when olfactory cues were used. Our results suggest that environmental cues are able to influence adult neurogenesis and that, in turn, newly generated neurons participate in olfactory integration, optimizing learning abilities of the animal, and thus its adaptation to its environment. Nevertheless, odor learning in adult insects cannot always be attributed to newly born neurons because neurogenesis is completed earlier in development in many insect species. In addition, many of the irradiated crickets performed significantly better than chance on the operant learning task. 相似文献
4.
Mushroom body (MB)-dependent olfactory learning in Drosophila provides a powerful model to investigate memory mechanisms. MBs integrate olfactory conditioned stimulus (CS) inputs with neuromodulatory reinforcement (unconditioned stimuli, US), which for aversive learning is thought to rely on dopaminergic (DA) signaling to DopR, a D1-like dopamine receptor expressed in MBs. A wealth of evidence suggests the conclusion that parallel and independent signaling occurs downstream of DopR within two MB neuron cell types, with each supporting half of memory performance. For instance, expression of the Rutabaga (Rut) adenylyl cyclase in γ neurons is sufficient to restore normal learning to rut mutants, whereas expression of Neurofibromatosis 1 (NF1) in α/β neurons is sufficient to rescue NF1 mutants. DopR mutations are the only case where memory performance is fully eliminated, consistent with the hypothesis that DopR receives the US inputs for both γ and α/β lobe traces. We demonstrate, however, that DopR expression in γ neurons is sufficient to fully support short- and long-term memory. We argue that DA-mediated CS-US association is formed in γ neurons followed by communication between γ and α/β neurons to drive consolidation. 相似文献
5.
Olga Ganeshina Jessika Erdmann Sandra Tiberi Misha Vorobyev Randolf Menzel 《Biology letters》2012,8(6):1023-1027
In mammals, memory formation and stabilization requires polymerization of actin. Here, we show that, in the honeybee, inhibition of actin polymerization within the brain centres involved in memory formation, the mushroom bodies (MBs), enhances associative olfactory memory. Local application of inhibitors of actin polymerization (Cytochalasin D or Latrunculin A) to the MBs 1 h before induction of long-term memory increased memory retention 2 and 24 h after the onset of training. Post-training application of Cytochalasin D also enhanced retention, indicating that memory consolidation is facilitated by actin depolymerization. We conclude that certain aspects of memory mechanisms could have been established independently in mammals and insects. 相似文献
6.
Background
It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis.Methodology/Principal Findings
Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb.Conclusion/Significance
We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory. 相似文献7.
Marie-Ange Chabaud Jean-Marc Devaud Minh-Hà Pham-Delègue Thomas Preat Laure Kaiser 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2006,192(12):1335-1348
Olfactory learning and memory processes in Drosophila have been well investigated with aversive conditioning, but appetitive conditioning has rarely been documented. Here, we
report for the first time individual olfactory conditioning of proboscis activity in restrained Drosophila melanogaster. The protocol was adapted from those developed for proboscis extension conditioning in the honeybee Apis mellifera. After establishing a scale of small proboscis movements necessary to characterize responses to olfactory stimulation, we
applied Pavlovian conditioning, with five trials consisting of paired presentation of a banana odour and a sucrose reward.
Drosophila showed conditioned proboscis activity to the odour, with a twofold increase of percentage of responses after the first trial.
No change occurred in flies experiencing unpaired presentations of the stimuli, confirming an associative basis for this form
of olfactory learning. The adenylyl cyclase mutant rutabaga did not exhibit learning in this paradigm. This protocol generated at least a short-term memory of 15 min, but no significant
associative memory was detected at 1 h. We also showed that learning performance was dependent on food motivation, by comparing
flies subjected to different starvation regimes. 相似文献
8.
Malun D Giurfa M Galizia CG Plath N Brandt R Gerber B Eisermann B 《Journal of neurobiology》2002,53(3):343-360
The mushroom bodies (MBs), a paired structure in the insect brain, play a major role in storing and retrieving olfactory memories. We tested whether olfactory learning and odor processing is impaired in honeybees in which MB subunits were partially ablated. Using hydroxyurea (HU) to selectively kill proliferating cells, we created honeybees with varying degrees of MB lesions. Three-dimensional reconstructions of brains were generated to analyze the drug-induced morphological changes. These reconstructions show that, with few exceptions, only the MBs were affected by the drug, while other brain areas remained morphometrically intact. Typically, lesions affected only the MB in one hemisphere of the brain. To preclude HU-induced physiologic deficits in the antennal lobe (AL) affecting olfactory learning, we measured the responses to odors in the AL using an in vivo calcium imaging approach. The response patterns did not differ between the AL of intact versus ablated brain sides within respective specimens. We, therefore, carried out side-specific classical discriminative olfactory conditioning of the proboscis extension reflex (PER) with control bees and with HU-treated bees with or without MB ablations. All experimental groups learned equally to discriminate and respond to a rewarded (CS+) but not to an unrewarded (CS-) conditioned stimulus during acquisition and retention tests. Thus, our results indicate that partial MB lesions do not affect this form of elemental olfactory learning. 相似文献
9.
Manipulations of context can affect learning and memory performance across species in many associative learning paradigms. Using taste cues to create distinct contexts for olfactory adaptation assays in the nematode Caenorhabditis elegans, we now show that performance in this associative learning paradigm is sensitive to context manipulations, and we investigate the mechanism(s) used for the integration of context cues in learning. One possibility is that the taste and olfactory stimuli are perceived as a combined, blended cue that the animals then associate with the unconditioned stimulus (US) in the same manner as with any other unitary conditioned stimuli (CS). Alternatively, an occasion-setting model suggests that the taste cues only define the appropriate context for olfactory memory retrieval without directly entering into the primary association. Analysis of genetic mutants demonstrated that the olfactory and context cues are sensed by distinct primary sensory neurons and that the animals' ability to use taste cues to modulate olfactory learning is independent from their ability to utilize these same taste cues for adaptation. We interpret these results as evidence for the occasion-setting mechanism in which context cues modulate primary Pavlovian association by functioning in a hierarchical manner to define the appropriate setting for memory recall. 相似文献
10.
Learning and memory is not an attribute of higher animals. Even Drosophila larvae are able to form and recall an association of a given odor with an aversive or appetitive gustatory reinforcer. As the Drosophila larva has turned into a particularly simple model for studying odor processing, a detailed neuronal and functional map of the olfactory pathway is available up to the third order neurons in the mushroom bodies. At this point, a convergence of olfactory processing and gustatory reinforcement is suggested to underlie associative memory formation. The dopaminergic system was shown to be involved in mammalian and insect olfactory conditioning. To analyze the anatomy and function of the larval dopaminergic system, we first characterize dopaminergic neurons immunohistochemically up to the single cell level and subsequent test for the effects of distortions in the dopamine system upon aversive (odor-salt) as well as appetitive (odor-sugar) associative learning. Single cell analysis suggests that dopaminergic neurons do not directly connect gustatory input in the larval suboesophageal ganglion to olfactory information in the mushroom bodies. However, a number of dopaminergic neurons innervate different regions of the brain, including protocerebra, mushroom bodies and suboesophageal ganglion. We found that dopamine receptors are highly enriched in the mushroom bodies and that aversive and appetitive olfactory learning is strongly impaired in dopamine receptor mutants. Genetically interfering with dopaminergic signaling supports this finding, although our data do not exclude on naïve odor and sugar preferences of the larvae. Our data suggest that dopaminergic neurons provide input to different brain regions including protocerebra, suboesophageal ganglion and mushroom bodies by more than one route. We therefore propose that different types of dopaminergic neurons might be involved in different types of signaling necessary for aversive and appetitive olfactory memory formation respectively, or for the retrieval of these memory traces. Future studies of the dopaminergic system need to take into account such cellular dissociations in function in order to be meaningful. 相似文献
11.
Memory impairment induced by cholinergic antagonists injected into the mushroom bodies of the honeybee 总被引:3,自引:0,他引:3
Valérie Lozano Catherine Armengaud Monique Gauthier 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2001,187(4):249-254
The role of honeybee central brain structures, suspected to be cholinergic, has been studied in learning and memory. The nicotinic antagonist mecamylamine and the muscarinic antagonist scopolamine were locally injected into the calyces and the alpha-lobes of mushroom bodies, and their effects on memory acquisition and retrieval were investigated using one-trial olfactory conditioning of the proboscis extension reflex. A strong impairment of the olfactory learning was noticed following mecamylamine injection into the mushroom body calyces. Mecamylamine and scopolamine disturbed retrieval processes when injected into the alpha-lobes of mushroom bodies but remain without effect on these processes when injected into the mushroom body calyces. These results emphasise the role of the cholinergic networks of the mushroom bodies in the formation and recall of memory in the honeybee. They suggest that the role of the brain structures in these processes is sequential. Mushroom body calyces involved in the associative process of olfactory learning could be relayed by the alpha-lobes for information retrieval. 相似文献
12.
Xia S Miyashita T Fu TF Lin WY Wu CL Pyzocha L Lin IR Saitoe M Tully T Chiang AS 《Current biology : CB》2005,15(7):603-615
BACKGROUND: Molecular and electrophysiological properties of NMDARs suggest that they may be the Hebbian "coincidence detectors" hypothesized to underlie associative learning. Because of the nonspecificity of drugs that modulate NMDAR function or the relatively chronic genetic manipulations of various NMDAR subunits from mammalian studies, conclusive evidence for such an acute role for NMDARs in adult behavioral plasticity, however, is lacking. Moreover, a role for NMDARs in memory consolidation remains controversial. RESULTS: The Drosophila genome encodes two NMDAR homologs, dNR1 and dNR2. When coexpressed in Xenopus oocytes or Drosophila S2 cells, dNR1 and dNR2 form functional NMDARs with several of the distinguishing molecular properties observed for vertebrate NMDARs, including voltage/Mg(2+)-dependent activation by glutamate. Both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. Hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. Importantly, we show that Pavlovian learning is disrupted in adults within 15 hr after transient induction of a dNR1 antisense RNA transgene. Extended training is sufficient to overcome this initial learning defect, but long-term memory (LTM) specifically is abolished under these training conditions. CONCLUSIONS: Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory. 相似文献
13.
In the present study we will try to single out several principles of the nervous system functioning essential for describing mechanisms of learning and memory basing on our own experimental investigation of cellular mechanisms of memory in the nervous system of gastropod molluscs and literature data: main changes in functioning due to learning occur in effectivity of synaptic inputs and in the intrinsic properties of postsynaptic neurons; due to learning some synaptic inputs of neurons selectively change its effectivity due to pre- and postsynaptic changes, but the induction of plasticity always starts in postsynapse, maintaining of long-term memory in postsynapse is also shown; reinforcement is not related to activity of the neural chain receptor-sensory neuron-interneuron-motoneuron-effector; reinforcement is mediated via activity of modulatory neurons, and in some cases can be exerted by a single neuron; activity of modulatory neurons is necessary for development of plastic modifications of behavior (including associative), but is not needed for recall of conditioned responses. At the same time, the modulatory neurons (in fact they constitute a neural reinforcement system) are necessary for recall of context associative memory; changes due to learning occur at least in two independent loci in the nervous system. A possibility for erasure of memory with participation of nitroxide is experimentally and theoretically based. 相似文献
14.
Dagmar Malun Martin Giurfa C. Giovanni Galizia Niels Plath Robert Brandt Bertram Gerber Beate Eisermann 《Developmental neurobiology》2002,53(3):343-360
The mushroom bodies (MBs), a paired structure in the insect brain, play a major role in storing and retrieving olfactory memories. We tested whether olfactory learning and odor processing is impaired in honeybees in which MB subunits were partially ablated. Using hydroxyurea (HU) to selectively kill proliferating cells, we created honeybees with varying degrees of MB lesions. Three‐dimensional reconstructions of brains were generated to analyze the drug‐induced morphological changes. These reconstructions show that, with few exceptions, only the MBs were affected by the drug, while other brain areas remained morphometrically intact. Typically, lesions affected only the MB in one hemisphere of the brain. To preclude HU‐induced physiologic deficits in the antennal lobe (AL) affecting olfactory learning, we measured the responses to odors in the AL using an in vivo calcium imaging approach. The response patterns did not differ between the AL of intact versus ablated brain sides within respective specimens. We, therefore, carried out side‐specific classical discriminative olfactory conditioning of the proboscis extension reflex (PER) with control bees and with HU‐treated bees with or without MB ablations. All experimental groups learned equally to discriminate and respond to a rewarded (CS+) but not to an unrewarded (CS?) conditioned stimulus during acquisition and retention tests. Thus, our results indicate that partial MB lesions do not affect this form of elemental olfactory learning. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 343–360, 2002 相似文献
15.
Balaban PM 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2007,93(5):521-530
In the present study, we will try to single out several principles of the nervous system functioning essential for describing the mechanisms of learning and memory, basing on our own experimental investigation of cellular mechanisms of memory in the nervous system of gastropod molluscs and literature data as follows: (1) Main changes in functioning due to learning occur in the interneurons; (2) Due to learning some synaptic inputs of command neurons selectively change its effectivity; (3) Reinforcement is not related to activity of the neural chain receptor-sensory neuron-interneuron-motoneuron-effector; reinforcement is mediated via activity of modulatory neurons, and in some cases can be exerted by a single neuron; (4) Activity of modulatory neurons is necessary for development of plastic modifications of behaviour (including associative), but is not needed for recall of conditioned responses. At the same time, the modulatory neurons (in fact they constitute a neural reinforcement system) are necessary for recall of context associative memory; (5) Changes due to learning occur at least in two independent loci in the nervous system. 相似文献
16.
Yehuda Ben-Shahar Gene E. Robinson 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2001,187(11):891-899
When not satiated prior to training, there were no differences between foragers and nurse honey bees in the acquisition of an appetitively based conditioned response in an olfactory associative learning assay, but when satiated foragers showed faster acquisition than did nurses. Satiation-related differences between foragers and nurses were more a function of behavioral state than age, because satiated precocious foragers also showed faster acquisition rates than did satiated nurse bees, despite their similar ages. Tests of sucrose responsiveness and retention of conditioned responses indicate that the observed performance differences between nurses and foragers were more likely due to differential sensitivity of sensory and motor processes related to satiation rather than differences in cognitive ability. 相似文献
17.
18.
Recent studies using functional optical imaging have revealed that cellular memory traces form in different areas of the insect brain after olfactory classical conditioning. These traces are revealed as increased calcium signals or synaptic release from defined neurons, and include a short-lived trace that forms immediately after conditioning in antennal lobe projection neurons, an early trace in dopaminergic neurons, and a medium-term trace in dorsal paired medial neurons. New molecular genetic tools have revealed that for normal behavioral memory performance, synaptic transmission from the mushroom body neurons is required only during retrieval, whereas synaptic transmission from dopaminergic neurons is required at the time of acquisition and synaptic transmission from dorsal paired medial neurons is required during the consolidation period. Such experimental results are helping to identify the types of neurons that participate in olfactory learning and when their participation is required. Olfactory learning often occurs alongside crossmodal interactions of sensory information from other modalities. Recent studies have revealed complex interactions between the olfactory and the visual senses that can occur during olfactory learning, including the facilitation of learning about subthreshold olfactory stimuli due to training with concurrent visual stimuli. 相似文献
19.
Brooks ES Greer CL Romero-Calderón R Serway CN Grygoruk A Haimovitz JM Nguyen BT Najibi R Tabone CJ de Belle JS Krantz DE 《Neuron》2011,72(2):316-329
Vesicular transporters are required for the storage of?all classical and amino acid neurotransmitters in synaptic vesicles. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male's position during copulation that is rescued by expression in KCs. Because prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning. 相似文献
20.
Gap junctions play an important role in the regulation of neuronal metabolism and homeostasis by serving as connections that enable small molecules to pass between cells and synchronize activity between cells. Although recent studies have linked gap junctions to memory formation, it remains unclear how they contribute to this process. Gap junctions are hexameric hemichannels formed from the connexin and pannexin gene families in chordates and the innexin (inx) gene family in invertebrates. Here we show that two modulatory neurons, the anterior paired lateral (APL) neuron and the dorsal paired medial (DPM) neuron, form heterotypic gap junctions within the mushroom body (MB), a learning and memory center in the Drosophila brain. Using RNA interference-mediated knockdowns of inx7 and inx6 in the APL and DPM neurons, respectively, we found that flies showed normal olfactory associative learning and intact anesthesia-resistant memory (ARM) but failed to form anesthesia-sensitive memory (ASM). Our results reveal that the heterotypic gap junctions between the APL and DPM neurons are an essential part of the MB circuitry for memory formation, potentially constituting a recurrent neural network to stabilize ASM. 相似文献