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Progress in Brain Research 2008The marine snail Aplysia has served for more than four decades as an important model system for neurobiological analyses of learning and memory. Until recently, it has... (Review)
Review
The marine snail Aplysia has served for more than four decades as an important model system for neurobiological analyses of learning and memory. Until recently, it has been believed that learning and memory in Aplysia were due predominately, if not exclusively, to presynaptic mechanisms. For example, two nonassociative forms of learning exhibited by Aplysia, sensitization and dishabituation of its defensive withdrawal reflex, have been previously ascribed to presynaptic facilitation of the connections between sensory and motor neurons that mediate the reflex. Recent evidence, however, indicates that postsynaptic mechanisms play a far more important role in learning and memory in Aplysia than formerly appreciated. In particular, dishabituation and sensitization depend on a rise in intracellular Ca(2+) in the postsynaptic motor neuron, postsynaptic exocytosis, and modulation of the functional expression of postsynaptic AMPA-type glutamate receptors. In addition, the expression of the persistent presynaptic changes that occur during intermediate- and long-term dishabituation and sensitization appears to require retrograde signals that are triggered by elevated postsynaptic Ca(2+). The model for learning-related synaptic plasticity proposed here for Aplysia is similar to current mammalian models. This similarity suggests that the cellular mechanisms of learning and memory have been highly conserved during evolution.
Topics: Animals; Aplysia; Avoidance Learning; Behavior, Animal; Memory; Models, Biological; Neuronal Plasticity; Serotonin; Synapses; Synaptic Transmission
PubMed: 18394481
DOI: 10.1016/S0079-6123(07)00017-9 -
Marine Drugs Feb 2016The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds... (Review)
Review
The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a successful phyla in the discovery of new marine natural products (MNPs). Over a 50-year period from 1963, 116 genera of mollusks contributed innumerous compounds, Aplysia being the most studied genus by MNP chemists. This genus includes 36 valid species and should be distinguished from all mollusks as it yielded numerous new natural products. Aplysia sea hares are herbivorous mollusks, which have been proven to be a rich source of secondary metabolites, mostly of dietary origin. The majority of secondary metabolites isolated from sea hares of the genus Aplysia are halogenated terpenes; however, these animals are also a source of compounds from other chemical classes, such as macrolides, sterols and alkaloids, often exhibiting cytotoxic, antibacterial, antifungal, antiviral and/or antifeedant activities. This review focuses on the diverse structural classes of secondary metabolites found in Aplysia spp., including several compounds with pronounced biological properties.
Topics: Animals; Aplysia; Aquatic Organisms; Biological Products; Drug Discovery; Humans; Mollusca; Secondary Metabolism
PubMed: 26907303
DOI: 10.3390/md14020039 -
Learning & Memory (Cold Spring Harbor,... 2023Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been...
Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk , with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior. To screen for other peptides that might also play roles in behavior, we observed immunoreactivity in individual neurons in the central nervous system of adult with antisera raised against the peptide FMRFamide and two mammalian peptides that are also found in , cholecystokinin (CCK) and neuropeptide Y (NPY), as well as serotonin (5HT). In addition, we observed staining of individual neurons with antisera raised against mammalian somatostatin (SOM) and peptide histidine isoleucine (PHI). However, genomic analysis has shown that these two peptides are not expressed in the nervous system, and we have therefore labeled the unknown peptides stained by these two antibodies as X and X There was an area at the anterior end of the cerebral ganglion that had staining by antisera raised against many different transmitters, suggesting that this may be a modulatory region of the nervous system. There was also staining for X and, in some cases, FMRFamide in the bag cell cluster of the abdominal ganglion. In addition, these and other studies have revealed a fairly high degree of colocalization of different neuropeptides in individual neurons, suggesting that the peptides do not just act independently but can also interact in different combinations to produce complex functions. The simple nervous system of is advantageous for further testing these ideas.
Topics: Animals; Aplysia; FMRFamide; Central Nervous System; Neuropeptides; Ganglia; Mammals
PubMed: 37442624
DOI: 10.1101/lm.053758.123 -
Scientific Reports May 2023Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein...
Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica, no receptors have been described in Aplysia, nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii, we found three putative elevenin GPCRs in Aplysia. We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.
Topics: Animals; Amino Acid Sequence; Aplysia; Neuropeptides; Receptors, G-Protein-Coupled; Disulfides
PubMed: 37169790
DOI: 10.1038/s41598-023-34596-9 -
Journal of the American Association For... Mar 2019This pharmacokinetic study was designed to determine the pharmacokinetics of enrofloxacin at 5 mg/kg when given to sea hares in their hemolymph. Enrofloxacin is a...
This pharmacokinetic study was designed to determine the pharmacokinetics of enrofloxacin at 5 mg/kg when given to sea hares in their hemolymph. Enrofloxacin is a commonly used antimicrobial in veterinary medicine and potentially could be used to treat sea hares exposed to susceptible bacterial species. We individually identified 8 juvenile and group housed them in an open seawater flow system at 14 to 18 °C; 2 served as untreated controls. The remaining 6 animals were injected into the hemocoel with 0.030 mL of 22.7 mg/mL enrofloxacin (average dose, 5 to 6 mg/kg). At each time point, 300 μL hemolymph was collected from the pedal hemolymph sinus and HPLC-analyzed for enrofloxacin and ciprofloxacin levels. Enrofloxacin was detected in all dosed animals, at an average peak concentration of 3 μg/mL in hemolymph, and remained in the body for 20.3 h with an average clearance of 0.19 μg × h/mL. No ciprofloxacin was detected in any in this study. Hemocoel injection appears to be an effective way to administer enrofloxacin to and reach clinically relevant concentrations. Enrofloxacin reached therapeutic target concentrations in when dosed according to the regimen described in the current report.
Topics: Animals; Anti-Bacterial Agents; Aplysia; Chromatography, High Pressure Liquid; Enrofloxacin; Laboratory Animal Science
PubMed: 30819273
DOI: 10.30802/AALAS-JAALAS-18-000072 -
The Biological Bulletin Jun 2006Until recently, investigations of the neurobiological substrates of simple forms of learning and memory in the marine snail Aplysia have focused mostly on plastic... (Review)
Review
Until recently, investigations of the neurobiological substrates of simple forms of learning and memory in the marine snail Aplysia have focused mostly on plastic changes that occur within the presynaptic sensory neurons. Here, I summarize the results of recent studies that indicate that exclusively presynaptic processes cannot account for simple forms of learning in Aplysia. In particular, I present evidence that postsynaptic mechanisms play a far more important role in nonassociative learning in Aplysia than has been appreciated before now. Moreover, I describe recent data that suggests the intriguing hypothesis that the persistent, learning-induced changes in Aplysia sensory neurons might depend critically on postsynaptic signals for their induction. Finally, I discuss the potential applicability of this hypothesis to learning-related synaptic plasticity in the mammalian brain.
Topics: Animals; Aplysia; Excitatory Postsynaptic Potentials; Habituation, Psychophysiologic; Learning; Models, Neurological; Neuronal Plasticity; Neurons, Afferent; Receptors, Glutamate; Synapses
PubMed: 16801500
DOI: 10.2307/4134563 -
Behavioural Brain Research Sep 2018Following exposure to aversive stimuli, organisms budget their behaviors by augmenting defensive responses and reducing/suppressing non-defensive behaviors. This...
Following exposure to aversive stimuli, organisms budget their behaviors by augmenting defensive responses and reducing/suppressing non-defensive behaviors. This budgeting process must be flexible to accommodate modifications in the animal's internal and/or external state that require the normal balance between defensive and non-defensive behaviors to be adjusted. When exposed to aversive stimuli, the mollusk Aplysia budgets its behaviors by concurrently enhancing defensive withdrawal reflexes (an elementary form of learning known as sensitization) and suppressing feeding. Sensitization and feeding suppression are consistently co-expressed following different training protocols and share common temporal domains, suggesting that they are interlocked. In this study, we attempted to uncouple the co-expression of sensitization and feeding suppression using: 1) manipulation of the animal's motivational state through prolonged food deprivation and 2) extended training with aversive stimuli that induces sensitization lasting for weeks. Both manipulations uncoupled the co-expression of the above behavioral changes. Prolonged food deprivation prevented the expression of sensitization, but not of feeding suppression. Following the extended training, sensitization and feeding suppression were co-expressed only for a limited time (i.e., 24 h), after which feeding returned to baseline levels as sensitization persisted for up to seven days. These findings indicate that sensitization and feeding suppression are not interlocked and that their co-expression can be uncoupled by internal (prolonged food deprivation) and external (extended aversive training) factors. The different strategies, by which the co-expression of sensitization and feeding suppression was altered, provide an example of how budgeting strategies triggered by an identical aversive experience can vary depending on the state of the organism.
Topics: Animals; Aplysia; Behavior, Animal; Feeding Behavior; Food Deprivation; Learning; Reflex
PubMed: 29704600
DOI: 10.1016/j.bbr.2018.04.040 -
Cellular and Molecular Life Sciences :... Mar 2011Associative learning in goal-directed behaviors, in contrast to reflexive behaviors, can alter processes of decision-making in the selection of appropriate action and... (Review)
Review
Associative learning in goal-directed behaviors, in contrast to reflexive behaviors, can alter processes of decision-making in the selection of appropriate action and its initiation, thereby enabling animals, including humans, to gain a predictive understanding of their external environment. In the mollusc Aplysia, recent studies on appetitive operant conditioning in which the animal learns about the positive consequences of its behavior have provided insights into this form of associative learning which, although ubiquitous, remains mechanistically poorly understood. The findings support increasing evidence that central circuit- and cell-wide sites other than chemical synaptic connections, including electrical coupling and membrane conductances controlling intrinsic neuronal excitability and underlying voltage-dependent plateauing or oscillatory mechanisms, may serve as the neural substrates for behavioral plasticity resulting from operant conditioning. Aplysia therefore continues to provide a model system for understanding learning and memory formation that enables establishing the neurobiological links between behavioral, network, and cellular levels of analysis.
Topics: Animals; Aplysia; Conditioning, Operant; Dopamine; Feeding Behavior; Reward
PubMed: 21042832
DOI: 10.1007/s00018-010-0570-9 -
Nature Methods Oct 2021Peptidergic dense-core vesicles are involved in packaging and releasing neuropeptides and peptide hormones-critical processes underlying brain, endocrine and exocrine...
Peptidergic dense-core vesicles are involved in packaging and releasing neuropeptides and peptide hormones-critical processes underlying brain, endocrine and exocrine function. Yet, the heterogeneity within these organelles, even for morphologically defined vesicle types, is not well characterized because of their small volumes. We present image-guided, high-throughput mass spectrometry-based protocols to chemically profile large populations of both dense-core vesicles and lucent vesicles for their lipid and peptide contents, allowing observation of the chemical heterogeneity within and between these two vesicle populations. The proteolytic processing products of four prohormones are observed within the dense-core vesicles, and the mass spectral features corresponding to the specific peptide products suggest three distinct dense-core vesicle populations. Notable differences in the lipid mass range are observed between the dense-core and lucent vesicles. These single-organelle mass spectrometry approaches are adaptable to characterize a range of subcellular structures.
Topics: Animals; Aplysia; High-Throughput Screening Assays; Machine Learning; Organelles; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34594032
DOI: 10.1038/s41592-021-01277-2 -
Analytical Chemistry Dec 2016A receptor binding class of d-amino acid-containing peptides (DAACPs) is formed in animals from an enzymatically mediated post-translational modification of ribosomally...
A receptor binding class of d-amino acid-containing peptides (DAACPs) is formed in animals from an enzymatically mediated post-translational modification of ribosomally translated all-l-amino acid peptides. Although this modification can be required for biological actions, detecting it is challenging because DAACPs have the same mass as their all-l-amino acid counterparts. We developed a suite of mass spectrometry (MS) protocols for the nontargeted discovery of DAACPs and validated their effectiveness using neurons from Aplysia californica. The approach involves the following three steps, with each confirming and refining the hits found in the prior step. The first step is screening for peptides resistant to digestion by aminopeptidase M. The second verifies the presence of a chiral amino acid via acid hydrolysis in deuterium chloride, labeling with Marfey's reagent, and liquid chromatography-mass spectrometry to determine the chirality of each amino acid. The third involves synthesizing the putative DAACPs and comparing them to the endogenous standards. Advantages of the method, the d-amino acid-containing neuropeptide discovery funnel, are that it is capable of detecting the d-form of any common chiral amino acid, and the first two steps do not require peptide standards. Using these protocols, we report that two peptides from the Aplysia achatin-like neuropeptide precursor exist as GdYFD and SdYADSKDEESNAALSDFA. Interestingly, GdYFD was bioactive in the Aplysia feeding and locomotor circuits but SdYADSKDEESNAALSDFA was not. The discovery funnel provides an effective means to characterize DAACPs in the nervous systems of animals in a nontargeted manner.
Topics: Amino Acids; Animals; Aplysia; CD13 Antigens; Mass Spectrometry; Neurons; Neuropeptides
PubMed: 27788334
DOI: 10.1021/acs.analchem.6b03658