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    • Teiichi Tanimura
    • 2019
    • Journal of Experimental Biology
    • Pt 7
    • Softness sensing and learning in Drosophila larvae
    • <p>Mechanosensation provides animals with important sensory information in addition to olfaction and gustation during feeding behavior. Here, we used Drosophila melanogaster larvae to investigate the role of softness sensing in behavior and learning. In the natural environment, larvae need to dig into soft foods for feeding. Finding foods that are soft enough to dig into is likely to be essential for their survival. We report that larvae can discriminate between different agar concentrations and prefer softer agar. Interestingly, we show that larvae on a harder surface search for a softer surface using memory associated with an odor, and that they evaluate foods by balancing softness and sweetness. These findings suggest that larvae integrate mechanosensory information with chemosensory input while foraging. Moreover, we found that the larval preference for softness is affected by genetic background. </p>
    • http://www.scopus.com/inward/record.url?scp=85064194422&partnerID=8YFLogxK
    • Anna Fejtova, Anna Fejtova
    • 2019
    • Journal of Neuroscience
    • 14
    • 2606-2619
    • A multiple piccolino-RIBEYE interaction supports plate-shaped synaptic ribbons in retinal neurons
    • <p>Active zones at chemical synapses are highly specialized sites for the regulated release of neurotransmitters. Despite a high degree of active zone protein conservation in vertebrates, every type of chemical synapse expresses a given set of protein isoforms and splice variants adapted to the demands on neurotransmitter release. So far, we know little about how specific active zone proteins contribute to the structural and functional diversity of active zones. In this study, we explored the nanodomain organization of ribbon-type active zones by addressing the significance of Piccolino, the ribbon synapse-specific splice variant of Piccolo, for shaping the ribbon structure. We followed up on previous results, which indicated that rod photoreceptor synaptic ribbons lose their structural integrity in a knockdown of Piccolino. Here, we demonstrate an interaction between Piccolino and the major ribbon component RIBEYE that supports plate-shaped synaptic ribbons in retinal neurons. In a detailed ultrastructural analysis of three different types of retinal ribbon synapses in Piccolo/Piccolino-deficient male and female rats, we show that the absence of Piccolino destabilizes the superstructure of plate-shaped synaptic ribbons, although with variable manifestation in the cell types examined. Our analysis illustrates how the expression of a specific active zone protein splice variant (e.g., Piccolino) contributes to structural diversity of vertebrate active zones. SIGNIFICANCE STATEMENT Retinal ribbon synapses are a specialized type of chemical synapse adapted for the regulated fast and tonic release of neurotransmitter. The hallmark of retinal ribbon synapses is the plate-shaped synaptic ribbon, which extends from the release site into the terminals' cytoplasm and tethers hundreds of synaptic vesicles. Here, we show that Piccolino, the synaptic ribbon specific splice variant of Piccolo, interacts with RIBEYE, the main component of synaptic ribbons. This interaction occurs via several PxDLS-like motifs located at the C terminus of Piccolino, which can connect multiple RIBEYE molecules. Loss of Piccolino disrupts the characteristic plate-shaped structure of synaptic ribbons, indicating a role of Piccolino in synaptic ribbon assembly. </p>
    • http://www.scopus.com/inward/record.url?scp=85064239611&partnerID=8YFLogxK
    • Bertram Gerber, Bertram Gerber
    • 2019
    • Current Opinion in Neurobiology
    • 146-154
    • Connectomics and function of a memory network
    • <p>The Drosophila larva is a relatively simple, 10 000-neuron study case for learning and memory with enticing analytical power, combining genetic tractability, the availability of robust behavioral assays, the opportunity for single-cell transgenic manipulation, and an emerging synaptic connectome of its complete central nervous system. Indeed, although the insect mushroom body is a much-studied memory network, the connectome revealed that more than half of the classes of connection within the mushroom body had escaped attention. The connectome also revealed circuitry that integrates, both within and across brain hemispheres, higher-order sensory input, intersecting valence signals, and output neurons that instruct behavior. Further, it was found that activating individual dopaminergic mushroom body input neurons can have a rewarding or a punishing effect on olfactory stimuli associated with it, depending on the relative timing of this activation, and that larvae form molecularly dissociable short-term, long-term, and amnesia-resistant memories. Together, the larval mushroom body is a suitable study case to achieve a nuanced account of molecular function in a behaviorally meaningful memory network.</p>
    • http://www.scopus.com/inward/record.url?scp=85055260920&partnerID=8YFLogxK
    • Bertram Gerber, Jörg Kleber, Bertram Gerber
    • 2019
    • Journal of Experimental Biology
    • Pt 19
    • Implications of the Sap47 null mutation for synapsin phosphorylation, longevity, climbing proficiency and behavioural plasticity in adult Drosophila
    • <p>The Sap47 gene of Drosophila melanogaster encodes a highly abundant 47 kDa synaptic vesicle-associated protein. Sap47 null mutants show defects in synaptic plasticity and larval olfactory associative learning but the molecular function of Sap47 at the synapse is unknown. We demonstrate that Sap47 modulates the phosphorylation of another highly abundant conserved presynaptic protein, synapsin. Site-specific phosphorylation of Drosophila synapsin has repeatedly been shown to be important for behavioural plasticity but it was not known where these phospho-synapsin isoforms are localized in the brain. Here, we report the distribution of serine-6-phosphorylated synapsin in the adult brain and show that it is highly enriched in rings of synapses in the ellipsoid body and in large synapses near the lateral triangle. The effects of knockout of Sap47 or synapsin on olfactory associative learning/memory support the hypothesis that both proteins operate in the same molecular pathway. We therefore asked if this might also be true for other aspects of their function. We show that knockout of Sap47 but not synapsin reduces lifespan, whereas knockout of Sap47 and synapsin, either individually or together, affects climbing proficiency, as well as plasticity in circadian rhythms and sleep. Furthermore, electrophysiological assessment of synaptic properties at the larval neuromuscular junction (NMJ) reveals increased spontaneous synaptic vesicle fusion and reduced paired pulse facilitation in Sap47 and synapsin single and double mutants. Our results imply that Sap47 and synapsin cooperate non-uniformly in the control of synaptic properties in different behaviourally relevant neuronal networks of the fruitfly. </p>
    • Ramona Grzeschik, Ramona Grzeschik
    • 2019
    • Cognition
    • 50-61
    • The contribution of visual attention and declining verbal memory abilities to age-related route learning deficits
    • <p>Our ability to learn unfamiliar routes declines in typical and atypical ageing. The reasons for this decline, however, are not well understood. Here we used eye-tracking to investigate how ageing affects people's ability to attend to navigationally relevant information and to select unique objects as landmarks. We created short routes through a virtual environment, each comprised of four intersections with two objects each, and we systematically manipulated the saliency and uniqueness of these objects. While salient objects might be easier to memorise than non-salient objects, they cannot be used as reliable landmarks if they appear more than once along the route. As cognitive ageing affects executive functions and control of attention, we hypothesised that the process of selecting navigationally relevant objects as landmarks might be affected as well. The behavioural data showed that younger participants outperformed the older participants and the eye-movement data revealed some systematic differences between age groups. Specifically, older adults spent less time looking at the unique, and therefore navigationally relevant, landmark objects. Both young and older participants, however, effectively directed gaze towards the unique and away from the non-unique objects, even if these were more salient. These findings highlight specific age-related differences in the control of attention that could contribute to declining route learning abilities in older age. Interestingly, route-learning performance in the older age group was more variable than in the young age group with some older adults showing performance similar to the young group. These individual differences in route learning performance were strongly associated with verbal and episodic memory abilities.</p>
    • http://www.scopus.com/inward/record.url?scp=85062157994&partnerID=8YFLogxK
    • Eckart D. Gundelfinger, Eckart D. Gundelfinger
    • 2019
    • bioRxiv
    • TRPV4 intracts with mitochondrial proteins and acts as a mitochondrial structure-function regulator
    • Christian König-Bethke, Thomas Niewalda, Bertram Gerber, Christian König, Afshin Khalili, Bertram Gerber
    • 2019
    • Biology Letters
    • 7
    • An optogenetic analogue of second-order reinforcement in Drosophila
    • <p>In insects, odours are coded by the combinatorial activation of ascending pathways, including their third-order representation in mushroom body Kenyon cells. Kenyon cells also receive intersecting input from ascending and mostly dopaminergic reinforcement pathways. Indeed, in Drosophila, presenting an odour together with activation of the dopaminergic mushroom body input neuron PPL1-01 leads to a weakening of the synapse between Kenyon cells and the approach-promoting mushroom body output neuron MBON-11. As a result of such weakened approach tendencies, flies avoid the shock-predicting odour in a subsequent choice test. Thus, increased activity in PPL1-01 stands for punishment, whereas reduced activity in MBON-11 stands for predicted punishment. Given that punishment-predictors can themselves serve as punishments of second order, we tested whether presenting an odour together with the optogenetic silencing of MBON-11 would lead to learned odour avoidance, and found this to be the case. In turn, the optogenetic activation of MBON-11 together with odour presentation led to learned odour approach. Thus, manipulating activity in MBON-11 can be an analogue of predicted, second-order reinforcement.</p>
    • http://www.scopus.com/inward/record.url?scp=85069261878&partnerID=8YFLogxK
    • Liv Mahnke, Frank Angenstein, Liv Mahnke, Frank Angenstein
    • 2019
    • Frontiers in Neuroscience
    • MAY
    • Electrical Stimulation of the Lateral Entorhinal Cortex Causes a Frequency-Specific BOLD Response Pattern in the Rat Brain
    • <p>Although deep brain stimulation of the entorhinal cortex has recently shown promise in the treatment of early forms of cognitive decline, the underlying neurophysiological processes remain elusive. Therefore, the lateral entorhinal cortex (LEC) was stimulated with trains of continuous 5 Hz and 20 Hz pulses or with bursts of 100 Hz pulses to visualize activated neuronal networks, i.e., neuronal responses in the dentate gyrus and BOLD responses in the entire brain were simultaneously recorded. Electrical stimulation of the LEC caused a wide spread pattern of BOLD responses. Dependent on the stimulation frequency, BOLD responses were only triggered in the amygdala, infralimbic, prelimbic, and dorsal peduncular cortex (5 Hz), or in the nucleus accumbens, piriform cortex, dorsal medial prefrontal cortex, hippocampus (20 Hz), and contralateral entorhinal cortex (100 Hz). In general, LEC stimulation caused stronger BOLD responses in frontal cortex regions than in the hippocampus. Identical stimulation of the perforant pathway, a fiber bundle projecting from the entorhinal cortex to the dentate gyrus, hippocampus proper, and subiculum, mainly elicited significant BOLD responses in the hippocampus but rarely in frontal cortex regions. Consequently, BOLD responses in frontal cortex regions are mediated by direct projections from the LEC rather than via signal propagation through the hippocampus. Thus, the beneficial effects of deep brain stimulation of the entorhinal cortex on cognitive skills might depend more on an altered prefrontal cortex than hippocampal function.</p>
    • http://www.scopus.com/inward/record.url?scp=85068535834&partnerID=8YFLogxK
    • Birgit Michels, Marcel Brosch, Bertram Gerber, Marcel Brosch, Katrin Franke, Bertram Gerber
    • 2019
    • Journal of Ethnopharmacology
    • 320-328
    • Rhodiola rosea root extract has antipsychotic-like effects in rodent models of sensorimotor gating
    • <p>Ethnopharmacological relevance: The plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce. Aim of the study: In this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract. Materials and methods: We tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders. Results: R. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits. Conclusions: The present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects.</p>
    • http://www.scopus.com/inward/record.url?scp=85061712060&partnerID=8YFLogxK
    • Rainer Pielot, Daniela Dieterich, Eckart D. Gundelfinger, Maria Andres-Alonso, Rainer Pielot, Daniela C Dieterich, Eckart D. Gundelfinger, Michael R. Kreutz
    • 2019
    • Neuron
    • 2
    • 217-234.e4
    • SynGO
    • <p>Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org).</p>
    • http://www.scopus.com/inward/record.url?scp=85068734308&partnerID=8YFLogxK
    • Magdalena Sauvage, Erika Atucha Trevino, Magdalena M. Sauvage, Erika Atucha
    • 2019
    • Journal of Neuroscience Methods
    • 108368
    • Single-cell memory trace imaging with immediate-early genes
    • <p>For the past decades, an increasing number of studies has taken advantage of molecular imaging methods involving the detection of immediate-early genes' (IEGs) expression for investigating neural substrates underlying plasticity processes and memory function. The detection of IEGs RNA by Fluorescent In-Situ Hybridization (FISH) yields single-cell as well as high temporal resolution and has recently enabled the mapping of medial temporal lobe subareas/subnetworks activity induced by single or multiple behavioural events in the same animal. After briefly reviewing the function and the ties of the typical IEGs (Fos, Zif268, Arc, Homer1a) used for mapping plasticity, we focus on discussing technical considerations vital for the successful detection of IEGs with FISH with emphasis on the design of RNA probes, the optimization of experimental conditions and the necessity for controls. Finally, we discuss recent developments in brain clearing methods that in combination with FISH detection of IEGs' expression allow for 3D imaging with single cell resolution as well as whole brain analyses. This, in parallel with the recent development of fMRI cognitive tasks in awake rats and the use of high resolution fMRI in humans, holds great promises for bridging further memory in humans and animals.</p>
    • http://www.scopus.com/inward/record.url?scp=85069858455&partnerID=8YFLogxK
    • Magdalena Sauvage, Magdalena M. Sauvage
    • 2019
    • Journal of Behavior Therapy and Experimental Psychiatry
    • Visuospatial computer game play after memory reminder delivered three days after a traumatic film reduces the number of intrusive memories of the experimental trauma
    • <p>Objective: The experience of intrusive memories is a core clinical symptom of posttraumatic stress disorder (PTSD), and can be distressing in its own right. Notions of dual task interference and reconsolidation-update mechanisms suggest novel approaches to target intrusive memories. This study tested the hypothesis that a single-session cognitive intervention (memory reminder task plus Tetris gameplay)would reduce the occurrence of experimental trauma memories even when delivered 3 days post-trauma. Critically, this study tested effects against two control groups: Reminder-only, and reminder plus another computer game (a form of Quiz). Methods: 86 healthy volunteers (59% female, age M = 24.35, SD = 4.59 years)watched a trauma film and then recorded their intrusive memories in a diary for 3 days (pre-intervention). They then returned to the lab. After presentation of visual reminder cues for the film plus a 10 min wait period (memory reminder task), participants were randomized into one of three task conditions (Tetris game play, Quiz game play, vs. reminder-only). They then kept the diary for a further 3 days (post-intervention). Results: As predicted, after the experimental manipulation, the reminder + Tetris group experienced significantly fewer intrusions than the reminder-only group (d = 1.37). Further, the reminder + Tetris group also experienced significantly fewer intrusions than the reminder + Quiz (d = 0.65)group. Contrary to predictions, the reminder + Quiz group experienced significantly fewer intrusions than the reminder-only group (d = 0.69). Prior to the experimental manipulation, there was no significant difference between groups in number of intrusions. Recognition memory test scores for facts of the trauma film after 6 days were comparable between groups. Conclusions: We demonstrated that 3 days after experimental trauma (i.e. after memory consolidation)an intervention comprising a reminder task prior to a 15 min cognitive interference task (one of two computer games)led to a reduction in intrusion occurrence compared to reminder only. We interpret and discuss our findings within the framework of supposed reconsolidation-update mechanisms and competition for limited (visuospatial)working memory resources. Should these effects hold true in clinical populations, this type of simple intervention approach could help contribute to reducing intrusive memories of trauma.</p>
    • http://www.scopus.com/inward/record.url?scp=85064615397&partnerID=8YFLogxK
    • Michael Schleyer, Naoko Toshima, Naoko Toshima, Michael Schleyer
    • 2019
    • Current Opinion in Insect Science
    • 39 - 44
    • Neuronal processing of amino acids in Drosophila: from taste sensing to behavioural regulation
    • Finding and feeding on appropriate food is crucial for all animals. Carbohydrates and amino acids are both essential nutrients, albeit with distinct roles: the former are the main energy source whereas the latter are the building blocks of proteins and are used as neurotransmitters. Despite their crucial role, neither the sensing nor the neuronal processing of amino acids is well understood. Studies in Drosophila melanogaster have only recently gained momentum in shedding new light on the molecular and neuronal mechanisms of peripheral and internal amino acid sensing, as well as the organization of amino acid feeding behaviour. Furthermore, amino acids have been shown to act as rewards in associative learning. Focusing on recent studies in Drosophila, we summarize what is known so far about the perception of, and the behavioural responses to, amino acids in insects, and try to identify key questions for future research.
    • http://www.scopus.com/inward/record.url?scp=85071453012&partnerID=8YFLogxK
    • Michael Schleyer, Emmanouil Paisios, Michael Schleyer
    • 2019
    • PLoS ONE
    • 10
    • Modulations of microbehaviour by associative memory strength in Drosophila larvae
    • <p>Finding food is a vital skill and a constant task for any animal, and associative learning of food-predicting cues gives an advantage in this daily struggle. The strength of the associations between cues and food depends on a number of parameters, such as the salience of the cue, the strength of the food reward and the number of joint cue-food experiences. We investigate what impact the strength of an associative odour-sugar memory has on the microbehaviour of Drosophila melanogaster larvae. We find that larvae form stronger memories with increasing concentrations of sugar or odour, and that these stronger memories manifest themselves in stronger modulations of two aspects of larval microbehaviour, the rate and the direction of lateral reorientation manoeuvres (so-called head casts). These two modulations of larval behaviour are found to be correlated to each other in every experiment performed, which is in line with a model that assumes that both modulations are controlled by a common motor output. Given that the Drosophila larva is a genetically tractable model organism that is well suited to the study of simple circuits at the single-cell level, these analyses can guide future research into the neuronal circuits underlying the translation of associative memories of different strength into behaviour, and may help to understand how these processes are organised in more complex systems.</p>
    • Martin Walter
    • 2019
    • Translational Psychiatry
    • 1
    • 28
    • Child sexual offenders show prenatal and epigenetic alterations of the androgen system
    • <p>Child sexual offending (CSO) places a serious burden on society and medicine and pedophilia (P) is considered a major risk factor for CSO. The androgen system is closely linked to sexual development and behavior. This study assessed markers of prenatal brain androgenization, genetic parameters of androgen receptor function, epigenetic regulation, and peripheral hormones in a 2 × 2 factorial design comprising the factors Offense (yes/no) and Pedophilia (yes/no) in analyzing blood samples from 194 subjects (57 P+CSO, 45 P−CSO, 20 CSO−P, and 72 controls) matched for age and intelligence. Subjects also received a comprehensive clinical screening. Independent of their sexual preference, child sexual offenders showed signs of elevated prenatal androgen exposure compared with non-offending pedophiles and controls. The methylation status of the androgen receptor gene was also higher in child sexual offenders, indicating lower functionality of the testosterone system, accompanied by lower peripheral testosterone levels. In addition, there was an interaction effect on methylation levels between offense status and androgen receptor functionality. Notably, markers of prenatal androgenization and the methylation status of the androgen receptor gene were correlated with the total number of sexual offenses committed. This study demonstrates alterations of the androgen system on a prenatal, epigenetic, and endocrine level. None of the major findings was specific for pedophilia, but they were for CSO. The findings support theories of testosterone-linked abnormalities in early brain development in delinquent behavior and suggest possible interactions of testosterone receptor gene methylation and plasma testosterone with environmental factors.</p>
    • http://www.scopus.com/inward/record.url?scp=85060157794&partnerID=8YFLogxK
    • Martin Walter
    • 2019
    • Journal of Affective Disorders
    • 371-379
    • Resting-state mapping of neural signatures of vulnerability to depression relapse
    • <p>Background: Patients with major depressive disorder (MDD) can frequently develop new depressive episodes after remission. However, the neural mechanisms underlying the increased risk for depressive relapse remain unclear. Herein, we aimed to explore whether the specific changes to regional and inter-regional spontaneous brain activities within DMN are associated with the course of episodes in pooled MDD patients. Methods: Resting-state functional magnetic resonance imaging was performed on patients with single-episode MDD (SEMDD, n = 30) and multiple-episode MDD (MEMDD, n = 54), and 71 age-, gender-, and educational level-matched healthy controls (HCs). We then accessed the differences in both the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity by using the right precuneus as the seed among different groups. Results: Compared to the MEMDD and HC groups, the SEMDD group exhibited increased fALFF values in the right subgenual anterior cingulate cortex and right middle temporal gyrus. Decreased fALFF values in the right thalamus in the MEMDD group were also identified relative to the SEMDD and HC group. The peak values of fALFF in the right precuneus showed a negative correlation with the number of depressive episodes across the entire pool of MDD patients. No correlation was identified between functional connectivity using the right precuneus as the seed and the number of depressive episodes for the pooled MDD patients. Limitations: Medication, a relatively small sample size, and hypothesis driven study. Conclusions: Our neuroimaging results identified depression relapse-associated neural signatures and also indicated the role of reduced emotional appraisals in the thalamus. It is now possible to believe that the regional activity not inter-regional connectivity within the DMN may be involved in the pathology of depression relapse.</p>
    • http://www.scopus.com/inward/record.url?scp=85062691939&partnerID=8YFLogxK
    • Alice Weiglein, Michael Schleyer, Nino Mancini, Bertram Gerber, Nino Mancini, Michael Schleyer, Bertram Gerber
    • 2019
    • Learning and Memory
    • 4
    • 109-120
    • One-trial learning in larval Drosophila
    • <p>Animals of many species are capable of "small data" learning, that is, of learning without repetition. Here we introduce larval Drosophila melanogaster as a relatively simple study case for such one-trial learning. Using odor-food associative conditioning, we first show that a sugar that is both sweet and nutritious (fructose) and sugars that are only sweet (arabinose) or only nutritious (sorbitol) all support appetitive one-trial learning. The same is the case for the optogenetic activation of a subset of dopaminergic neurons innervating the mushroom body, the memory center of the insects. In contrast, no one-trial learning is observed for an amino acid reward (aspartic acid). As regards the aversive domain, one-trial learning is demonstrated for high-concentration sodium chloride, but is not observed for a bitter tastant (quinine). Second, we provide follow-up, parametric analyses of odor-fructose learning. Specifically, we ascertain its dependency on the number and duration of training trials, the requirements for the behavioral expression of one-trial odor-fructose memory, its temporal stability, and the feasibility of one-trial differential conditioning. Our results set the stage for a neurogenetic analysis of one-trial learning and define the requirements for modeling mnemonic processes in the larva.</p>
    • http://www.scopus.com/inward/record.url?scp=85063625323&partnerID=8YFLogxK
    • Andreas Widmann
    • 2019
    • Journal of Cognitive Neuroscience
    • 8
    • 1110-1125
    • Presentation Probability of Visual-Auditory Pairs Modulates Visually Induced Auditory Predictions
    • Predictions about forthcoming auditory events can be established on the basis of preceding visual information. Sounds being incongruent to predictive visual information have been found to elicit an enhanced negative ERP in the latency range of the auditory N1 compared with physically identical sounds being preceded by congruent visual information. This so-called incongruency response (IR) is interpreted as reduced prediction error for predicted sounds at a sensory level. The main purpose of this study was to examine the impact of probability manipulations on the IR. We manipulated the probability with which particular congruent visual–auditory pairs were presented (83/17 vs. 50/50 condition). This manipulation led to two conditions with different strengths of the association of visual with auditory information. A visual cue was presented either above or below a fixation cross and was followed by either a high- or low-pitched sound. In 90% of trials, the visual cue correctly predicted the subsequent sound. In one condition, one of the sounds was presented more frequently (83% of trials), whereas in the other condition both sounds were presented with equal probability (50% of trials). Therefore, in the 83/17 condition, one congruent combination of visual cue and corresponding sound was presented more frequently than the other combinations presumably leading to a stronger visual–auditory association. A significant IR for unpredicted compared with predicted but otherwise identical sounds was observed only in the 83/17 condition, but not in the 50/50 condition, where both congruent visual cue–sound combinations were presented with equal probability. We also tested whether the processing of the prediction violation is dependent on the task relevance of the visual information. Therefore, we contrasted a visual–auditory matching task with a pitch discrimination task. It turned out that the task only had an impact on the behavioral performance but not on the prediction error signals. Results suggest that the generation of visual-to-auditory sensory predictions is facilitated by a strong association between the visual cue and the predicted sound (83/17 condition) but is not influenced by the task relevance of the visual information.
    • Andreas Widmann
    • 2019
    • Journal of Cognitive Neuroscience
    • Action-intention based and stimulus-regularity based predictions: Same or different?
    • We act on the environment to produce desired effects, but we also adapt to the environmental demands by learning what to expect next, based on experience: How do action-based predictions and sensory predictions relate to each other? We explore this by implementing a self-generation oddball paradigm, where participants performed random sequences of left and right button presses to produce frequent standard and rare deviant tones. By manipulating the action-tone association, as well as the likelihood of a button-press over the other one, we compare ERP effects evoked by the intention to produce a specific tone, tone regularity, and both intention and regularity. We show that the N1b and Tb components of the N1 response are modulated by violations of tone regularity only. However, violations of action intention as well as of regularity elicit MMN responses, which occur similarly in all three conditions. Regardless of whether the predictions at sensory levels were based on either intention, regularity, or both, the tone deviance was further and equally well detected at hierarchically higher processing level, as reflected in similar P3a effects between conditions. We did not observe additive prediction errors when intention and regularity were violated concurrently, suggesting the two integrate despite presumably having independent generators. Even though they are often discussed as individual prediction sources in the literature, this study represents to our knowledge the first to directly compare them. Finally, these results show how in the context of action, our brain can easily switch between top-down intention-based expectations and bottom-up regularity cues, in order to efficiently predict future events.
    • Motoharu Yoshida, Motoharu Yoshida
    • 2019
    • Hippocampus
    • 9
    • 817-835
    • Switching between persistent firing and depolarization block in individual rat CA1 pyramidal neurons
    • <p>The hippocampal formation plays a role in mnemonic tasks and epileptic discharges in vivo. In vitro, these functions and malfunctions may relate to persistent firing (PF) and depolarization block (DB), respectively. Pyramidal neurons of the CA1 field have previously been reported to engage in either PF or DB during cholinergic stimulation. However, it is unknown whether these cells constitute disparate populations of neurons. Furthermore, it is unclear which cell-specific peculiarities may mediate their diverse response properties. However, it has not been shown whether individual CA1 pyramidal neurons can switch between PF and DB states. Here, we used whole cell patch clamp in the current clamp mode on in vitro CA1 pyramidal neurons from acutely sliced rat tissue to test various intrinsic properties which may provoke individual cells to switch between PF and DB. We found that individual cells could switch from PF to DB, in a cholinergic agonist concentration dependent manner and depending on the parameters of stimulation. We also demonstrate involvement of TRPC and potassium channels in this switching. Finally, we report that the probability for DB was more pronounced in the proximal than in the distal half of CA1. These findings offer a potential mechanism for the stronger spatial modulation in proximal, compared to distal CA1, as place field formation was shown to be affected by DB. Taken together, our results suggest that PF and DB are not mutually exclusive response properties of individual neurons. Rather, a cell's response mode depends on a variety of intrinsic properties, and modulation of these properties enables switching between PF and DB.</p>
    • http://www.scopus.com/inward/record.url?scp=85061991073&partnerID=8YFLogxK
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