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Kemenes, G.

Publications and source records attributed to Kemenes, G..

5 recordsLinked to original sources

History-dependent ephaptic interactions in paired olfactory receptor neurons

Olfactory sensing begins with the transduction of odors into receptor currents on the dendrites of olfactory receptor neurons (ORNs). In insects and many other arthropods, ORNs are grouped stereotypically in hair-like sensilla on the surface of olfactory organs, enabling mutual inhibition through non-synaptic ephaptic interactions (NSIs). Given the electrical, and therefore virtually instantaneous, nature of NSIs, it has been hypothesized that they contribute to processing fast temporal elements of mixed odor plumes. Here, we present single sensillum recordings and computational modeling that characterize NSIs during short offset dual-odor stimulations in the olfactory sensilla of adult female Drosophila melanogaster. We find in the experiments that the magnitude of inhibition between co-housed ORNs cannot be predicted by their instantaneous activity (firing rate) alone. It is adaptation-dependent, with strong effects only occurring when the inhibited ORN is adapted. This limits the usefulness of NSIs for fast odor processing when ORNs lack time to adapt. We reproduced the observed phenomena in a computational model and use this model to explain how the adaptation-dependence of NSI-mediated inhibition arises from nonlinearities in neural responses. We conclude that NSIs are unlikely to support the encoding of fast temporal dynamics in mixed odor stimuli, instead contributing to slower peripheral processing, supporting roles such as novelty detection. More broadly, we demonstrate how the nonlinear interactions of fairly simple electrical components lead to non-intuitive results, offering insight into the longstanding debate around ephaptic interactions in other systems, such as the mammalian CNS.

neuroscience↗

Histone acetyltransferase activity of CREB-binding protein is essential for synaptic plasticity in Lymnaea

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 role CBP plays in CREB-initiated plastic changes in Lymnaea. In this study, we characterized the Lymnaea CBP (LymCBP) gene and investigated the roles it plays in synaptic plasticity involved in regulating feeding behaviors. Similar to CBPs of other species, LymCBP possesses functional domains, such as KIX domain, which is essential for interaction with CREB and was shown to regulate long-term memory (LTM). In situ hybridization showed that the staining patterns of LymCBP mRNA in the central nervous system were very similar to those of Lymnaea CREB1 (LymCREB1). A particularly strong LymCBP mRNA signal was observed in the Cerebral Giant Cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors such as curcumin, anacardic acid and garcinol. Preincubation of Lymnaea CNSs with these HAT inhibitors blocked cAMP-induced long-term potentiation between the CGC and the follower B1 motoneuron. We therefore suggest that HAT activity of LymCBP in the CGCs is a key factor in synaptic plasticity contributing to LTM after classical conditioning.

neuroscience↗

A proteomics database for CNS proteins of the great pond snail Lymnaea stagnalis

Applications of key technologies in biomedical research, such as qRT-PCR or LC-MS based proteomics, are generating large biological (-omics) data sets which are useful for the identification and quantification of biomarkers involved in molecular mechanisms of 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 learning and memory, ageing and age-related as well as amyloid-{beta} induced memory decline. In this investigation, we used a bioinformatics approach to designing and benchmarking a comprehensive CNS proteomics database (LymCNS-PDB) for the identification of proteins from the Central Nervous System (CNS) of Lymnaea stagnalis 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 an existing published Lymnaea stagnalis transcriptomics database. The blast-style MMSeq2 software was used to match all translated sequences to sequences for molluscan proteins (including Lymnaea stagnalis and other molluscs) available from UniProtKB. LymCNS-PDB, which contains 9,628 identified matched proteins, was then benchmarked by performing LC-MS based proteomics analysis with proteins isolated from the CNS of Lymnaea stagnalis. MS/MS analysis using the LymCNS-PDB database led to the identification of 3,810 proteins while 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 to identify a plethora of protein interactomes involved in several CNS functions in Lymnaea stagnalis including learning and memory, aging-related memory decline and others.

bioinformatics↗

Interneuronal mechanisms underlying a learning-induced switch in a sensory response that anticipates changes in behavioural outcomes

How an animal responds to a particular sensory stimulus will to a great extent depend on prior experience associated with that stimulus. For instance, aversive associative learning may lead to a change in the predicted outcomes, which suppresses the behavioural response to an otherwise rewarding stimulus. However, the neuronal mechanisms of how aversive learning can result in the suppression of even a vitally important innate behaviour is not well understood. Here we used the model system of Lymnaea stagnalis to address the question of how an anticipated aversive outcome can alter the behavioural response to a previously effective feeding stimulus. We found that aversive classical conditioning with sucrose as the CS (conditioned stimulus) and strong touch as the aversive US (unconditioned stimulus) reverses the decision so that the same salient feeding stimulus inhibits feeding, rather than activating it. Key to the understanding of the neural mechanism underlying this switch in the behavioural response is the PlB (pleural buccal) extrinsic interneuron of the feeding network whose modulatory effects on the feeding circuit inhibit feeding. After associative aversive training, PlB is excited by sucrose to reverse its effects on the feeding response. Aversive associative learning induces a persistent change in the electrical properties of PlB that is both sufficient and necessary for the switch in the behavioural output. In addition, the strong touch used as the US during the associative training protocol can also serve as a sensitizing stimulus to lead to an enhanced defensive withdrawal response to a mild touch stimulus. This non-associative effect of the strong touch is probably based on the facilitated excitatory output of a key identified interneuron of the defensive withdrawal network, PeD12.

neuroscience↗

A central control circuit for encoding perceived food value

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 such 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 towards 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.

neuroscience↗