Biology subjects

Arslan, C.

Publications and source records attributed to Arslan, C..

6 recordsLinked to original sources

bioRxiv2026

Mechanism and subunit-dependence of disease-associated lurcher mutation in AMPA-type glutamate receptors

AMPA receptors are glutamate-activated neuroreceptors responsible for the majority of fast excitatory neurotransmission in vertebrate brains. Activity-dependent changes in their functional and trafficking properties underpin cognitive processes such as learning and memory formation. In the past 15 years, a number of mutations within AMPA receptor genes have been identified as disease-causing leading to some form of neurodevelopmental delay. Here, we focused on one such mutation called lurcher, resulting from a change of the third Ala in the highly conserved SYTANLAAF motif to Thr. We determined functional consequences of lurcher mutation in homomeric AMPA receptors composed of subunits GluA1 or GluA2. In GluA1 subunit, lurcher mutation has been identified as a hotspot in a large cohort of patients with neurodevelopmental disorders. We confirm previously established lurcher phenotype characterised by slower deactivation and desensitization kinetics as well as more profound block of desensitization compared to the wild-type (WT) homomers. We show that these effects are more pronounced in GluA2 than GluA1 homomers. Lurcher phenotypes are attenuated, but still present, in more physiologically abundant heteromeric AMPA receptors composed of two GluA1 lurcher and two GluA2 WT subunits (GluA1 lc/GluA2 WT). Schild analysis indicates lurcher enhances activity of AMPA receptors by primarily changing the efficiency with which they open their ion channel upon glutamate binding rather than by changing affinity for glutamate. Perampanel, the only widely licensed drug that targets AMPA receptors, is an anti-convulsant that acts as a non-competitive inhibitor. We show it continues to inhibit GluA1 lc/GluA2 WT heteromeric receptors and that its IC50 depends on the auxiliary subunits associated with the heteromers. Specifically, stargazin (TARP {gamma}-2) brings the IC50 for perampanel into the submicromolar range, just like in the WT receptors.

neuroscience↗

bioRxiv2026

Neural reinstatement of features in audiovisual working memory indicatesobject-based retrieval

Selective attention allows us to prioritize or retrieve task-relevant features and items from working memory. However, previous work has largely relied on unisensory paradigms, leaving open the question of how attentional mechanisms act on audiovisual working memory representations. Here, using an EEG-based audiovisual delayed-match-to-sample task, we investigate whether attention to audiovisual working memory contents operates on the level of individual unisensory features or bound cross-modal objects. On each trial, participants memorized an audiovisual item. At test, they were randomly presented with either an auditory, visual, or an audiovisual probe stimulus and indicated whether the latter matched their working memory content. Compared with recalling the entire audiovisual object, recall of unisensory visual or auditory features resulted in poorer behavioral performance and elevated midfrontal theta power. Multivariate pattern analyses (MVPA) showed that task-irrelevant feature representations were retrieved in both auditory and visual probe trials, consistent with object-based retrieval. Moreover, these results shed light on the representational structure underlying cross-modal feature storage in working memory, suggesting that audiovisual features are stored as bound objects and that attentional selection of individual object features in one modality spreads to cross-modal object features in another modality. In task conditions where such incidental recall of task-irrelevant features is detrimental to task performance, this places greater demands on cognitive control mechanisms.

neuroscience↗

bioRxiv2025

Tracking neural representations of attended and unattended features in multisensory working memory over time

Working memory supports goal-directed behavior by maintaining task-relevant information. However, a growing number of studies shows that even task-irrelevant features are automatically encoded and can interfere with the recall of task-relevant information. While this phenomenon is well documented in unisensory contexts, it remains unclear whether and how task-irrelevant information persists in multisensory working memory. We examine the role of cross-modal binding by tracking the dynamic neural representation of audio-visual objects under varying selective attention conditions, using an EEG-based audio-visual delayed-match-to-sample task. Participants attended to either auditory or visual features (selective attention), or to both features (conjunction) of two sequential audio-visual items and subsequently compared those task-relevant features to an audio-visual probe. Further, to investigate the influence of bottom-up factors on cross-modal binding, we manipulated spatial congruency by presenting both features from either the same (i.e., in the center) or from disparate positions. Behaviorally, task-irrelevant features interfered with performance even under selective attention, consistent with automatic cross-modal binding and encoding into working memory. This interference was even stronger with spatially disparate presentation, suggesting that bottom-up attentional dynamics strengthen cross-modal bindings and their subsequent storage. Condition-level representational similarity analysis (RSA) showed that EEG activity patterns under selective attention more closely resembled those of conjunction trials than unisensory trials, indicating that task-irrelevant features were incorporated into multisensory object-level representations. This conjunction-similarity persisted in attend-visual trials, but declined over time in attend-auditory trials, reflecting partial filtering of task-irrelevant orientations. Crucially, activity patterns never shifted fully towards an auditory-only profile, indicating that irrelevant visual features were not fully excluded. In addition, feature-level RSA corroborated that both sound frequency-specific and orientation-specific information were present in EEG activity patterns, irrespective of the attended modality. Overall, these results demonstrate the persistence of task-irrelevant information in multisensory working memory and offer critical insights into how attentional processes shape its representational architecture.

neuroscience↗

bioRxiv2024

Strikingly different neurotransmitter release strategies in dopaminergic subclasses

Neuronal function is intimately tied to axodendritic polarity. Neurotransmitter release, for example, is usually the role of the axon. There are widespread exceptions to this rule, however, including many mammalian neuronal types that can release neurotransmitter from their dendrites. In the mouse olfactory bulb, closely related subclasses of dopaminergic interneuron differ markedly in their polarity, with one subtype lacking an axon entirely. These axon-bearing and anaxonic dopaminergic subclasses have distinct developmental profiles and sensory responses, but how their fundamental polarity differences translate to functional outputs remains entirely unknown. Here, we provide anatomical evidence for distinct neurotransmitter release strategies among these closely related dopaminergic subtypes: anaxonic cells release from their dendrites, while axon-bearing neurons release exclusively from their intermittently myelinated axon. These structural differences are linked to a clear functional distinction: anaxonic, but not axon-bearing dopaminergic neurons are capable of self-inhibition. Our findings suggest that variations in polarity can produce striking distinctions in neuronal outputs, and that even closely related neuronal subclasses may play entirely separate roles in sensory information processing.

neuroscience↗

bioRxiv2024

The Interplay Between Multisensory Processing and Attention in Working Memory: Behavioral and Neural Indices of Audio-Visual Object Storage

Although real-life events are multisensory, how audio-visual objects are stored in working memory is an open question. At a perceptual level, evidence shows that both top-down and bottom-up attentional processes can play a role in multisensory interactions. To understand how attention and multisensory processes interact in working memory, we designed an audio-visual delayed match-to-sample task in which participants were presented with one or two audio-visual memory items, followed by an audio-visual probe. In three different blocks, participants were instructed to either (a) attend to the auditory features, (b) attend to the visual features, or (c) attend to both auditory and visual features. Participants were instructed to indicate whether the task-relevant features of the probe matched one of the task-relevant feature(s) or objects in working memory. Behavioral results showed interference from task-irrelevant features, suggesting bottom-up integration of audio-visual features and their automatic encoding into working memory, irrespective of their task relevance. Yet, ERP analyses revealed no evidence for active maintenance of these task-irrelevant features, while they clearly taxed greater attentional resources during recall. Notably, alpha oscillatory activity revealed that linking information between auditory and visual modalities required more attentional demands at retrieval. Overall, these results offer critical insights into how and at which processing stage multisensory interactions occur in working memory. Public Significance StatementCurrent working memory research is dominated by investigations of the visual domain. Yet, understanding how more complex representations, e.g., based on multisensory inputs, are formed, stored, and recalled is crucial to obtaining a more realistic understanding of working memory function. The present study shows that when confronted with audio-visual inputs at the same time and location, features from both modalities are combined into a working memory representation, irrespective of their task relevance. During maintenance, alpha oscillations serve to flexibly gate information flow in the cortex, allowing for the re-distribution of attentional resources between modalities depending on their task-relevance. Notably, when the task instructions explicitly involve the storage of audio-visual objects as a whole, recall requires more attentional resources.

neuroscience↗

bioRxiv2023

Boosting sleep slow waves suppresses dreaming

Previous findings suggest a negative correlation between slow oscillations (SO) in posterior brain regions and dreaming. Here we use a precise closed-loop auditory stimulation (CLAS) procedure to causally test whether slow oscillations suppress dreaming. Our results show that boosting posterior SO during NREM sleep decreases the likelihood of dreaming as compared to no SO boosting. This study provides the first causal evidence for the neural correlates of dreaming.

neuroscience↗