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1.
Artigo em Inglês | MEDLINE | ID: mdl-38940930

RESUMO

Evidence has been accumulating that elements of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) system are missing in non-chordate genomes, which is at odds with the partial sequence-, immunohistochemical-, and physiological data in the literature. Multilevel experiments were performed on the great pond snail (Lymnaea stagnalis) to explore the role of PACAP in invertebrates. Screening of neuronal transcriptome and genome data did not reveal homologs to the elements of vertebrate PACAP system. Despite this, immunohistochemical investigations with an anti-human PAC1 receptor antibody yielded a positive signal in the neuronal elements in the heart. Although Western blotting of proteins extracted from the nervous system found a relevant band for PACAP-38, immunoprecipitation and mass spectrometric analyses revealed no corresponding peptide fragments. Similarly to the effects reported in vertebrates, PACAP-38 significantly increased cAMP synthesis in the heart and had a positive ionotropic effect on heart preparations. Moreover, it significantly modulated the effects of serotonin and acetylcholine. Homologs to members of Cluster B receptors, which have shared common evolutionary origin with the vertebrate PACAP receptors, PTHRs, and GCGRs, were identified and shown not to be expressed in the heart, which does not support a potential role in the mediation of PACAP-induced effects. Our findings support the notion that the PACAP system emerged after the protostome-deuterostome divergence. Using antibodies against vertebrate proteins is again highlighted to have little/no value in invertebrate studies. The physiological effects of vertebrate PACAP peptides in protostomes, no matter how similar they are to those in vertebrates, should be considered non-specific.

2.
Sci Adv ; 9(12): eadd3403, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36961898

RESUMO

Long-term memory formation is energetically costly. Neural mechanisms that guide an animal to identify fruitful associations therefore have important survival benefits. Here, we elucidate a circuit mechanism in Lymnaea, which enables past memory to shape new memory formation through changes in perception. Specifically, strong classical conditioning drives a positive shift in perception that facilitates the robust learning of a subsequent and otherwise ineffective weak association. Circuit dissection approaches reveal the neural control network responsible, characterized by a mutual inhibition motif. This both sets perceptual state and acts as the master controller for gating new learning. Pharmacological circuit manipulation in vivo fully substitutes for strong paradigm learning, shifting the network into a more receptive state to enable subsequent weak paradigm learning. Thus, perceptual change provides a conduit to link past and future memory storage. We propose that this mechanism alerts animals to learning-rich periods, lowering the threshold for new memory acquisition.


Assuntos
Aprendizagem , Memória , Animais , Aprendizagem/fisiologia , Memória/fisiologia , Memória de Longo Prazo , Percepção
3.
MethodsX ; 10: 102117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970021

RESUMO

In the field of neuroscience and ecotoxicology, there is a great need for investigating the effect(s) of a variety of different chemicals (e.g., pharmacologically active compounds, pesticides, neurotransmitters, modulators) at different biological levels. Different contractile tissue preparations have provided excellent model systems for in vitro pharmacological experiments for a long time. However, such investigations usually apply mechanical force transducer-based approaches. Thus, a rapid, easy, cheap, digital, and reproducible in vitro pharmacological method based on an effective, 'non-invasive' (compared to the force-transducer approaches), refraction-based optical recording approach and isolated heart preparations was developed.•A versatile and unique refraction-based optical recording system with a Java application was developed.•The recording system was tested and validated on isolated heart preparations obtained from the widely used invertebrate model organism, the great pond snail (Lymnaea stagnalis).•The recording system illustrates the progression of technology from the mechanical force transducer system and can represent a suitable tool in ecotoxicology or neuroscience.

4.
Front Behav Neurosci ; 16: 1005867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353518

RESUMO

Investigations of the molecular mechanisms of long-term associative memory have revealed key roles for a number of highly evolutionarily conserved molecular pathways in a variety of different vertebrate and invertebrate model systems. One such system is the pond snail Lymnaea stagnalis, in which, like in other systems, the transcription factors CREB1 and CREB2 and the enzyme NOS play essential roles in the consolidation of long-term associative memory. More recently, epigenetic control mechanisms, such as DNA methylation, histone modifications, and control of gene expression by non-coding RNAs also have been found to play important roles in all model systems. In this minireview, we will focus on how, in Lymnaea, even a single episode of associative learning can activate CREB and NO dependent cascades due to the training-induced up- or downregulation of the expression levels of recently identified short and long non-coding RNAs.

5.
FASEB J ; 36(11): e22593, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36251357

RESUMO

In eukaryotes, CREB-binding protein (CBP), a coactivator of CREB, functions both as a platform for recruiting other components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. We previously showed that the transcriptional activity of cAMP-responsive element binding protein (CREB) plays a crucial role in neuronal plasticity in the pond snail Lymnaea stagnalis. However, there is no information on the molecular structure and HAT activity of CBP in the Lymnaea central nervous system (CNS), hindering an investigation of its postulated role in long-term memory (LTM). Here, we characterize the Lymnaea CBP (LymCBP) gene and identify a conserved domain of LymCBP as a functional HAT. Like CBPs of other species, LymCBP possesses functional domains, such as the KIX domain, which is essential for interaction with CREB and was shown to regulate LTM. In-situ hybridization showed that the staining patterns of LymCBP mRNA in CNS are very similar to those of Lymnaea CREB1. A particularly strong LymCBP mRNA signal was observed in the cerebral giant cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, the key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of the LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors. Preincubation of the CNS with such inhibitors blocked cAMP-induced synaptic facilitation between the CGC and an identified follower motoneuron of the feeding system. Taken together, our findings suggest a role for the HAT activity of LymCBP in synaptic plasticity in the feeding circuitry.


Assuntos
Proteína de Ligação a CREB , Lymnaea , Animais , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Sistema Nervoso Central/metabolismo , Cromatina/metabolismo , Lymnaea/genética , Lymnaea/metabolismo , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo
6.
J Exp Biol ; 225(7)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35403696

RESUMO

Applications of key technologies in biomedical research, such as qRT-PCR or LC-MS-based proteomics, are generating large biological (-omics) datasets which are useful for the identification and quantification of biomarkers in any research area of interest. Genome, transcriptome and proteome databases are already available for a number of model organisms including vertebrates and invertebrates. However, there is insufficient information available for protein sequences of certain invertebrates, such as the great pond snail Lymnaea stagnalis, a model organism that has been used highly successfully in elucidating evolutionarily conserved mechanisms of memory function and dysfunction. Here, we used a bioinformatics approach to designing and benchmarking a comprehensive central nervous system (CNS) proteomics database (LymCNS-PDB) for the identification of proteins from the CNS of Lymnaea by LC-MS-based proteomics. LymCNS-PDB was created by using the Trinity TransDecoder bioinformatics tool to translate amino acid sequences from mRNA transcript assemblies obtained from a published Lymnaea transcriptomics database. The blast-style MMSeq2 software was used to match all translated sequences to UniProtKB sequences for molluscan proteins, including those from Lymnaea and other molluscs. LymCNS-PDB contains 9628 identified matched proteins that were benchmarked by performing LC-MS-based proteomics analysis with proteins isolated from the Lymnaea CNS. MS/MS analysis using the LymCNS-PDB database led to the identification of 3810 proteins. Only 982 proteins were identified by using a non-specific molluscan database. LymCNS-PDB provides a valuable tool that will enable us to perform quantitative proteomics analysis of protein interactomes involved in several CNS functions in Lymnaea, including learning and memory and age-related memory decline.


Assuntos
Biologia Computacional , Lymnaea , Animais , Benchmarking , Sistema Nervoso Central , Cromatografia Líquida , Lymnaea/genética , Proteínas/metabolismo , Espectrometria de Massas em Tandem
7.
Sci Rep ; 11(1): 3594, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574420

RESUMO

Long natural antisense transcripts (NATs) have been demonstrated in significant numbers in a variety of eukaryotic organisms. They are particularly prevalent in the nervous system suggesting their importance in neural functions. However, the precise physiological roles of the overwhelming majority of long NATs remain unclear. Here we report on the characterization of a novel molluscan nitric oxide synthase (NOS)-related long non-coding NAT (Lym-NOS1AS). This NAT is spliced and polyadenylated and is transcribed from the non-template strand of the Lym-NOS1 gene. We demonstrate that the Lym-NOS1AS is co-expressed with the sense Lym-NOS1 mRNA in a key neuron of memory network. Also, we report that the Lym-NOS1AS is temporally and spatially regulated by one-trial conditioning leading to long term memory (LTM) formation. Specifically, in the cerebral, but not in the buccal ganglia, the temporal pattern of changes in Lym-NOS1AS expression after training correlates with the alteration of memory lapse and non-lapse periods. Our data suggest that the Lym-NOS1AS plays a role in the consolidation of nitric oxide-dependent LTM.


Assuntos
Memória de Longo Prazo/fisiologia , Neurônios/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética , Animais , Regulação da Expressão Gênica/genética , Moluscos/genética , Moluscos/fisiologia , Óxido Nítrico Sintase , RNA Mensageiro/genética
8.
Curr Biol ; 31(8): 1754-1761.e3, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33571436

RESUMO

Sensory cues in the natural environment predict reward or punishment, important for survival. For example, the ability to detect attractive tastes indicating palatable food is essential for foraging while the recognition of inedible substrates prevents harm. While some of these sensory responses are innate, they can undergo fundamental changes due to prior experience associated with the stimulus. However, the mechanisms underlying such behavioral switching of an innate sensory response at the neuron and network levels require further investigation. We used the model learning system of Lymnaea stagnalis1-3 to address the question of how an anticipated aversive outcome reverses the behavioral response to a previously effective feeding stimulus, sucrose. Key to the switching mechanism is an extrinsic inhibitory interneuron of the feeding network, PlB (pleural buccal4,5), which is inhibited by sucrose to allow a feeding response. After multi-trial aversive associative conditioning, pairing sucrose with strong tactile stimuli to the head, PlB's firing rate increases in response to sucrose application to the lips and the feeding response is suppressed; this learned response is reversed by the photoinactivation of a single PlB. A learning-induced persistent change in the cellular properties of PlB that results in an increase rather than a decrease in its firing rate in response to sucrose provides a neurophysiological mechanism for this behavioral switch. A key interneuron, PeD12 (Pedal-Dorsal 12), of the defensive withdrawal network5,6 does not mediate the conditioned suppression of feeding, but its facilitated output contributes to the sensitization of the withdrawal response.


Assuntos
Interneurônios , Animais , Comportamento Alimentar , Lymnaea , Neurônios , Sacarose
9.
J Gerontol A Biol Sci Med Sci ; 76(6): 975-982, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-33453110

RESUMO

With the increase of life span, normal aging and age-related memory decline are affecting an increasing number of people; however, many aspects of these processes are still not fully understood. Although vertebrate models have provided considerable insights into the molecular and electrophysiological changes associated with brain aging, invertebrates, including the widely recognized molluscan model organism, the great pond snail (Lymnaea stagnalis), have proven to be extremely useful for studying mechanisms of aging at the level of identified individual neurons and well-defined circuits. Its numerically simpler nervous system, well-characterized life cycle, and relatively long life span make it an ideal organism to study age-related changes in the nervous system. Here, we provide an overview of age-related studies on L. stagnalis and showcase this species as a contemporary choice for modeling the molecular, cellular, circuit, and behavioral mechanisms of aging and age-related memory impairment.


Assuntos
Envelhecimento/fisiologia , Modelos Animais de Doenças , Lymnaea/crescimento & desenvolvimento , Transtornos da Memória/fisiopatologia , Fatores Etários , Animais , Epigênese Genética/genética , Lymnaea/genética , Lymnaea/fisiologia , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/fisiologia , Neurônios/fisiologia
10.
Invert Neurosci ; 20(3): 9, 2020 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-32449011

RESUMO

Modelling of human aging, age-related memory loss, and neurodegenerative diseases has developed into a progressive area in invertebrate neuroscience. Gold standard molluscan neuroscience models such as the sea hare (Aplysia californica) and the great pond snail (Lymnaea stagnalis) have proven to be attractive alternatives for studying these processes. Until now, A. californica has been the workhorse due to the enormous set of publicly available transcriptome and genome data. However, with growing sequence data, L. stagnalis has started to catch up with A. californica in this respect. To contribute to this and inspire researchers to use molluscan species for modelling normal biological aging and/or neurodegenerative diseases, we sequenced the whole transcriptome of the central nervous system of L. stagnalis and screened for the evolutionary conserved homolog sequences involved in aging and neurodegenerative/other diseases. Several relevant molecules were identified, including for example gelsolin, presenilin, huntingtin, Parkinson disease protein 7/Protein deglycase DJ-1, and amyloid precursor protein, thus providing a stable genetic background for L. stagnalis in this field. Our study supports the notion that molluscan species are highly suitable for studying molecular, cellular, and circuit mechanisms of the mentioned neurophysiological and neuropathological processes.


Assuntos
Envelhecimento/metabolismo , Transtornos da Memória/metabolismo , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Transcriptoma , Envelhecimento/genética , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Lymnaea , Transtornos da Memória/genética , Doenças Neurodegenerativas/genética
11.
Commun Biol ; 2: 242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31263786

RESUMO

Interference-based forgetting occurs when new information acquired either before or after a learning event attenuates memory expression (proactive and retroactive interference, respectively). Multiple learning events often occur in rapid succession, leading to competition between consolidating memories. However, it is unknown what factors determine which memory is remembered or forgotten. Here, we challenge the snail, Lymnaea, to acquire two consecutive similar or different memories and identify learning-induced changes in neurons of its well-characterized motor circuits. We show that when new learning takes place during a stable period of the original memory, proactive interference only occurs if the two consolidating memories engage the same circuit mechanisms. If different circuits are used, both memories survive. However, any new learning during a labile period of consolidation promotes retroactive interference and the acquisition of the new memory. Therefore, the effect of interference depends both on the timing of new learning and the underlying neuronal mechanisms.


Assuntos
Aprendizagem/fisiologia , Lymnaea/fisiologia , Consolidação da Memória/fisiologia , Memória/fisiologia , Animais , Comportamento Animal , Rememoração Mental , Fatores de Tempo
12.
Sci Adv ; 4(11): eaau9180, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30474061

RESUMO

Hunger state can substantially alter the perceived value of a stimulus, even to the extent that the same sensory cue can trigger antagonistic behaviors. How the nervous system uses these graded perceptual shifts to select between opposed motor patterns remains enigmatic. Here, we challenged food-deprived and satiated Lymnaea to choose between two mutually exclusive behaviors, ingestion or egestion, produced by the same feeding central pattern generator. Decoding the underlying neural circuit reveals that the activity of central dopaminergic interneurons defines hunger state and drives network reconfiguration, biasing satiated animals toward the rejection of stimuli deemed palatable by food-deprived ones. By blocking the action of these neurons, satiated animals can be reconfigured to exhibit a hungry animal phenotype. This centralized mechanism occurs in the complete absence of sensory retuning and generalizes across different sensory modalities, allowing food-deprived animals to increase their perception of food value in a stimulus-independent manner to maximize potential calorific intake.


Assuntos
Comportamento de Escolha/fisiologia , Comportamento Alimentar/fisiologia , Privação de Alimentos/fisiologia , Fome/fisiologia , Lymnaea/fisiologia , Neurônios/fisiologia , Animais , Modelos Neurológicos , Vias Neurais
13.
Sci Rep ; 8(1): 12227, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111831

RESUMO

Single cell mass spectrometry (MS) is uniquely positioned for the sequencing and identification of peptides in rare cells. Small peptides can take on different roles in subcellular compartments. Whereas some peptides serve as neurotransmitters in the cytoplasm, they can also function as transcription factors in the nucleus. Thus, there is a need to analyze the subcellular peptide compositions in identified single cells. Here, we apply capillary microsampling MS with ion mobility separation for the sequencing of peptides in single neurons of the mollusk Lymnaea stagnalis, and the analysis of peptide distributions between the cytoplasm and nucleus of identified single neurons that are known to express cardioactive Phe-Met-Arg-Phe amide-like (FMRFamide-like) neuropeptides. Nuclei and cytoplasm of Type 1 and Type 2 F group (Fgp) neurons were analyzed for neuropeptides cleaved from the protein precursors encoded by alternative splicing products of the FMRFamide gene. Relative abundances of nine neuropeptides were determined in the cytoplasm. The nuclei contained six of these peptides at different abundances. Enabled by its relative enrichment in Fgp neurons, a new 28-residue neuropeptide was sequenced by tandem MS.


Assuntos
Espectrometria de Massas/métodos , Análise de Célula Única/métodos , Sequência de Aminoácidos , Animais , FMRFamida/metabolismo , Interneurônios/metabolismo , Espaço Intracelular , Lymnaea/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Peptídeos/análise , Peptídeos/metabolismo , Frações Subcelulares/metabolismo
14.
Sci Adv ; 4(7): eaat1357, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29978045

RESUMO

Action potential shape is a major determinant of synaptic transmission, and mechanisms of spike tuning are therefore of key functional significance. We demonstrate that synaptic activity itself modulates future spikes in the same neuron via a rapid feedback pathway. Using Ca2+ imaging and targeted uncaging approaches in layer 5 neocortical pyramidal neurons, we show that the single spike-evoked Ca2+ rise occurring in one proximal bouton or first node of Ranvier drives a significant sharpening of subsequent action potentials recorded at the soma. This form of intrinsic modulation, mediated by the activation of large-conductance Ca2+/voltage-dependent K+ channels (BK channels), acts to maintain high-frequency firing and limit runaway spike broadening during repetitive firing, preventing an otherwise significant escalation of synaptic transmission. Our findings identify a novel short-term presynaptic plasticity mechanism that uses the activity history of a bouton or adjacent axonal site to dynamically tune ongoing signaling properties.


Assuntos
Potenciais de Ação/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Sinapses/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Potenciais Evocados/efeitos dos fármacos , Feminino , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Patch-Clamp , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar
15.
Sci Rep ; 8(1): 3950, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29500383

RESUMO

Although single-trial induced long-term memories (LTM) have been of major interest in neuroscience, how LTM can form after a single episode of learning remains largely unknown. We hypothesized that the removal of molecular inhibitory constraints by microRNAs (miRNAs) plays an important role in this process. To test this hypothesis, first we constructed small non-coding RNA (sncRNA) cDNA libraries from the CNS of Lymnaea stagnalis subjected to a single conditioning trial. Then, by next generation sequencing of these libraries, we identified a specific pool of miRNAs regulated by training. Of these miRNAs, we focussed on Lym-miR-137 whose seed region shows perfect complementarity to a target sequence in the 3' UTR of the mRNA for CREB2, a well-known memory repressor. We found that Lym-miR-137 was transiently up-regulated 1 h after single-trial conditioning, preceding a down-regulation of Lym-CREB2 mRNA. Furthermore, we discovered that Lym-miR-137 is co-expressed with Lym-CREB2 mRNA in an identified neuron with an established role in LTM. Finally, using an in vivo loss-of-function approach we demonstrated that Lym-miR-137 is required for single-trial induced LTM.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Aprendizagem , Lymnaea/fisiologia , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação para Baixo , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , RNA Mensageiro/genética , Proteínas Repressoras/genética , Transcrição Gênica , Regulação para Cima
16.
FEBS Lett ; 591(9): 1236-1246, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28337747

RESUMO

Amyloid-ß (Aß) peptides are implicated in the causation of memory loss, neuronal impairment, and neurodegeneration in Alzheimer's disease. Our recent work revealed that Aß 1-42 and Aß 25-35 inhibit long-term memory (LTM) recall in Lymnaea stagnalis (pond snail) in the absence of cell death. Here, we report the characterization of the active species prepared under different conditions, describe which Aß species is present in brain tissue during the behavioral recall time point and relate the sequence and structure of the oligomeric species to the resulting neuronal properties and effect on LTM. Our results suggest that oligomers are the key toxic Aß1-42 structures, which likely affect LTM through synaptic plasticity pathways, and that Aß 1-42 and Aß 25-35 cannot be used as interchangeable peptides.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Lymnaea/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/ultraestrutura , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Hemolinfa/efeitos dos fármacos , Hemolinfa/fisiologia , Lymnaea/fisiologia , Memória de Longo Prazo/fisiologia , Microscopia Eletrônica de Transmissão , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Patch-Clamp , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/ultraestrutura
17.
Sci Rep ; 6: 30182, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27443509

RESUMO

Amyloid ß1-42 (Aß1-42) plays a central role in Alzheimer's disease. The link between structure, assembly and neuronal toxicity of this peptide is of major current interest but still poorly defined. Here, we explored this relationship by rationally designing a variant form of Aß1-42 (vAß1-42) differing in only two amino acids. Unlike Aß1-42, we found that the variant does not self-assemble, nor is it toxic to neuronal cells. Moreover, while Aß1-42 oligomers impact on synaptic function, vAß1-42 does not. In a living animal model system we demonstrate that only Aß1-42 leads to memory deficits. Our findings underline a key role for peptide sequence in the ability to assemble and form toxic structures. Furthermore, our non-toxic variant satisfies an unmet demand for a closely related control peptide for Aß1-42 cellular studies of disease pathology, offering a new opportunity to decipher the mechanisms that accompany Aß1-42-induced toxicity leading to neurodegeneration.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Doenças Neurodegenerativas/metabolismo , Sequência de Aminoácidos , Proteínas Amiloidogênicas/metabolismo , Amiloidose/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Transtornos da Memória/metabolismo , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Ratos
18.
Nat Commun ; 7: 11793, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27257106

RESUMO

During goal-directed decision-making, animals must integrate information from the external environment and their internal state to maximize resource localization while minimizing energy expenditure. How this complex problem is solved by the nervous system remains poorly understood. Here, using a combined behavioural and neurophysiological approach, we demonstrate that the mollusc Lymnaea performs a sophisticated form of decision-making during food-searching behaviour, using a core system consisting of just two neuron types. The first reports the presence of food and the second encodes motivational state acting as a gain controller for adaptive behaviour in the absence of food. Using an in vitro analogue of the decision-making process, we show that the system employs an energy management strategy, switching between a low- and high-use mode depending on the outcome of the decision. Our study reveals a parsimonious mechanism that drives a complex decision-making process via regulation of levels of tonic inhibition and phasic excitation.


Assuntos
Comportamento Apetitivo/fisiologia , Tomada de Decisões/fisiologia , Lymnaea/fisiologia , Neurônios/fisiologia , Animais , Comportamento Alimentar/fisiologia , Objetivos , Técnicas In Vitro , Motivação , Inibição Neural/fisiologia
19.
Neurobiol Aging ; 36(10): 2838-49, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163984

RESUMO

During aging, the Ca(2+)-sensitive slow afterhyperpolarization (sAHP) of hippocampal neurons is known to increase in duration. This change has also been observed in the serotonergic cerebral giant cells (CGCs) of the pond snail Lymnaea stagnalis, but has yet to be characterized. In this article, we confirm that there is a reduction in firing rate, an increase in the duration of the sAHP, and an alteration in the strength and speed of spike frequency adaptation in the CGCs during aging, a finding that is compatible with an increase in the sAHP current. We go on to show that age-related changes in the kinetics of spike frequency adaptation are consistent with a reduction in Ca(2+) clearance from the cell, which we confirm with Ca(2+) imaging and pharmacological manipulation of the sodium calcium exchanger. These experiments suggest that the sodium calcium exchanger may be switching to a reverse-mode configuration in the CGCs during aging.


Assuntos
Potenciais de Ação/fisiologia , Envelhecimento/fisiologia , Neurônios Serotoninérgicos/fisiologia , Trocador de Sódio e Cálcio/fisiologia , Animais , Cálcio/metabolismo , Células Cultivadas , Sistema Nervoso Central/citologia , Lymnaea , Técnicas de Patch-Clamp , Neurônios Serotoninérgicos/metabolismo
20.
Sci Rep ; 5: 10614, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26024049

RESUMO

Amyloid beta (Aß) induced neuronal death has been linked to memory loss, perhaps the most devastating symptom of Alzheimer's disease (AD). Although Aß-induced impairment of synaptic or intrinsic plasticity is known to occur before any cell death, the links between these neurophysiological changes and the loss of specific types of behavioral memory are not fully understood. Here we used a behaviorally and physiologically tractable animal model to investigate Aß-induced memory loss and electrophysiological changes in the absence of neuronal death in a defined network underlying associative memory. We found similar behavioral but different neurophysiological effects for Aß 25-35 and Aß 1-42 in the feeding circuitry of the snail Lymnaea stagnalis. Importantly, we also established that both the behavioral and neuronal effects were dependent upon the animals having been classically conditioned prior to treatment, since Aß application before training caused neither memory impairment nor underlying neuronal changes over a comparable period of time following treatment.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Memória de Longo Prazo , Plasticidade Neuronal , Neurônios/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Morte Celular/efeitos dos fármacos , Condicionamento Clássico , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Hemolinfa/metabolismo , Transtornos da Memória/metabolismo , Memória de Longo Prazo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Agregação Patológica de Proteínas , Caramujos , Fatores de Tempo
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