Biology subjects

Toth, B.

Publications and source records attributed to Toth, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Neuronal FICD shapes motivated behavior through modulation of dopamine receptor dynamics

Motivated behaviors rely on dopaminergic signaling, which in turn depends on the correct folding and trafficking of receptors through the endoplasmic reticulum (ER). Within the ER, the AMPylase enzyme FICD acts as a molecular rheostat through its modification of the chaperone BiP, dynamically tuning the organelle's responsiveness to folding perturbations and cellular stress. While the biochemistry of FICD is well-established, its role in complex animal behavior remains poorly understood. Here, we identify FICD as a conserved contributor to the generation of motivated behavior. In Drosophila, pan-neuronal knockdown of dFic significantly reduces feeding, spontaneous locomotion, and reward-seeking behavior. These alterations occur without disrupting circadian architecture, motor capacity, or homeostatic hunger, indicating a specific loss of motivational drive. Depleting dFic within subsets of dopamine receptor-expressing (Dop1R1) neurons recapitulates these behavioral alterations. Transcriptomic profiling reveals that dFic depletion does not induce a canonical unfolded protein response, pointing to a specific post-transcriptional alteration rather than global ER stress. At the molecular level, dysregulated dFic alters the localization and abundance of Dop1R1. Finally, we demonstrate that this regulatory axis is evolutionarily conserved, as loss of FICD similarly diminishes motivated behaviors in C. elegans and mice. Together, these findings implicate FICD in the generation of motivated behavior and link dynamic control of ER proteostasis to dopamine-receptor maturation.

neuroscience↗

bioRxiv2026

Specialized layer 5 cortical terminals target functional thalamic spines

Dendritic spines are ubiquitous morpho-functional elements of excitatory synaptic transmission and plasticity. Whether axo-spinous communication exists in the thalamus is presently unclear. Here we find that layer 5 (L5) corticothalamic terminals arising from frontal cortices selectively target thalamic spines with classical head and neck dimensions. The synapses of the L5 axo-spinous contacts were enriched in GluR1 subunit of AMPA receptor and their size correlated with their spine head volume. Synaptic stimulation of thalamic spines resulted in compartmentalized Ca2+ responses similar to that of hippocampal spines. Optogenetic activation of the frontal L5-thalamus pathway had strong impact on thalamic spiking even at high stimulation frequencies and could selectively recruit a subnetwork of thalamic cells in a behavioral state dependent manner. Optogenetic interference with the small L5-thalamic pathway perturbed motor learning. Our study reveals a hitherto unrecognized, effective top-down communication channel between the frontal cortex and thalamus that involves highly variable axo-spinous contacts.

neuroscience↗

bioRxiv2026

The impact of seizures on REM sleep and the cholinergic pedunculopontine nucleus in a mouse model of Dravet Syndrome

Sleep disruption is a common and burdensome feature in epilepsy, with rapid eye movement (REM) sleep particularly affected. While sleep disturbances in epilepsy patients are multifactorial, clinical evidence suggests that recent seizures acutely impair REM sleep architecture. To investigate this relationship, we used a haploinsufficient mouse model of Dravet Syndrome, which allows experimental control of seizure timing and burden. We found that hyperthermia-induced seizures profoundly decreased subsequent sleep, specifically impairing REM entry. In vivo fiber photometry revealed acute, seizure-induced activation of cholinergic neurons in the pedunculopontine nucleus (PPN), a brainstem structure critical for REM entry. We additionally found that repeated seizures triggered anatomical changes in the PPN, including reduced cholinergic neuron number and significant hypertrophy of remaining cholinergic neurons. These results suggest seizures are a driver of both acute and chronic disruption of PPN cholinergic networks, which in turn impair REM sleep in epilepsy. Our findings identify the PPN as a potential therapeutic target for interventions to address sleep-related sequelae of seizures.

neuroscience↗

bioRxiv2025

Genome-wide characterization of upper Fraser River sockeye salmon identifies a region of major differentiation between run timing groups in the Stuart River Watershed

Effective wildlife conservation and management depends on a thorough understanding of both neutral and adaptive intraspecific genomic variation. Although population structure is often well understood for many ecologically or economically important species, the extensive population genomic resources required to characterize putatively adaptive variation, for example in punctuated genomic regions, is typically only recently available in many species, if at all. Here we explore recently published whole-genome resequencing data in the upper Fraser River and identify a large island of divergence separating populations with different run timings in the Nechako Watershed. The island of divergence at approximately 56.3-58.0 Mbp of Chr18 has extended homozygosity and reduced Tajimas D in specific populations of the upper Fraser River. These include the Nadina and Stellako River sockeye, as well as the Stuart-Summer run timing group, but not the geographically proximal Early Stuart sockeye. In the populations without the Stuart-Summer haploblock, genetic variation looks more similar to elsewhere throughout the chromosome. When investigating the gene content of this region, importantly it was determined to contain the leucine rich-repeat containing 9-like (lrrc9-like) gene and surrounding homeologous region to the lrrc9 region of Chr12, known to contain a conserved and selected island of divergence that has been associated with life history traits and run timing throughout the species range. By also inspecting the samples in the present work at the Chr12 haploblock, three genotypic states were observed throughout the region, although the Stuart River run timing groups contained mainly the reference haplotype. Using similar methods, no other regions of major differentiation were observed in the available samples for the Chilcotin or Quesnel River systems. These results provide additional evidence for the importance of both homeologous regions holding lrrc9 and lrrc9-like in different geographic regions and underscore the uniqueness of upper Fraser River sockeye in this potentially adaptive island of divergence.

genomics↗

bioRxiv2025

Human newborns form musical predictions based on rhythmic but not melodic structure

The ability to anticipate rhythmic and melodic structures in music is considered a fundamental human trait, present across all cultures and predating linguistic comprehension in human development. Yet, it remains unclear the extent to which this ability is already developed at birth. Here, we used temporal response functions to assess rhythmic and melodic neural encoding in newborns (N = 49) exposed to classical monophonic musical pieces (real condition) and control stimuli with shuffled tones and inter-onset intervals (shuffled condition). We computationally quantified context-based rhythmic and melodic expectations and dissociated these high-level processes from low-level acoustic tracking, such as local changes in timing and pitch. We observed encoding of probabilistic rhythmic expectations only in response to real but not shuffled music. This proves newborns ability to rely on rhythmic statistical regularities to generate musical expectations. We found no evidence for the tracking of melodic information demonstrating a downweighing of this dimension compared to the rhythmic one. This study provides neurophysiological evidence that the capacity to track statistical regularities in music is present at birth and driven by rhythm. Melodic tracking, in contrast, may receive more weight through development with exposure to signals relevant to communication, such as speech and music. SignificancePerception and appreciation of music stem from humans universal ability to track sequential pitch and timing variations, forming musical melodies and rhythms. To investigate the neurobiological origins of this capacity, we measured neural encoding of rhythm and melody in newborns listening to naturalistic music. We demonstrate a precocious ability to track high-level rhythmic statistical regularities beyond low-level acoustic features. Conversely, melodic tracking is virtually absent at birth, likely emerging with later exposure to pitch-varying signals such as speech and music. This reveals that newborns gradually rely on different sound dimensions to start making sense of the auditory environment. While rhythm and melody are both universal components of music, they do not emerge in parallel but instead develop along distinct timelines.

neuroscience↗

bioRxiv2024

What are you talking about? Representation of the Topic of Speech in the Human Brain

A sentence outside context provides very restricted information to the listener. Real understanding requires one to be able to place it within the sequence of sentences forming a coherent "story" and just as importantly, within ones general knowledge of the "topic". Here we demonstrate the existence of functional brain networks robustly sensitive to the topic of ca. 6-minute-long coherent newspaper articles. Main network hubs are located in parietal and temporal brain regions. These networks changed very slowly during the course of the article, consistent with their involvement in representing the topic rather than the story aspect of the context. Because even the meaning of words can depend on the topic (see e.g., the word "shuttle" in transportation and weaving) the topic-sensitive network must also be intimately linked with the mental lexicon underlying language comprehension. Significance StatementWhen we listen to someone talking, our brain continuously integrates the speech stream with our general knowledge associated with the topic. While this is a central process of comprehension, it is still unclear how the brain maintains the relevant representations. Here we demonstrate the existence of a cortical network, which is sensitive to the topic of the speech just heard. This network may form the neural substrate for "topic representation" in the brain. Understanding how such representations are maintained and accessed would let us reveal the computations enabling rapid linguistic integration, a key process in human communication.

neuroscience↗

bioRxiv2024

Temporal expectations modulate coupling between frontal and sensory brain areas

Temporal prediction enhances perceptual processing by aligning neural excitability with expected sensory events. While local oscillatory mechanisms are known to support timing, less is understood about how large-scale functional brain networks dynamically coordinate predictive processes. In particular, it remains unclear how functional connectivity (FC)--the integration of information into network hubs--differs during expectation formation (post-cue) versus outcome evaluation (post-target), and how this varies across levels of predictability. To investigate this, we recorded electroencephalogram (EEG) while participants performed a cued auditory target-detection task with varying temporal predictability (80% and 50%). Event-related potential (ERP) results revealed that implicit temporal predictability primarily modulated later evaluative processes (P3b, frontal negativity), rather than early sensory components, consistent with context updating under uncertainty. FC was analyzed using a data-driven approach based on Normalized Directed Transfer Entropy (NDTE) applied to EEG difference waveforms between high- and low-predictability conditions. Connectivity was examined separately for the post-cue and post-target periods to distinguish prediction and evaluation phases. Behaviorally, higher temporal predictability facilitated faster reaction times. Connectivity analyses revealed largely overlapping but somewhat distinct network dynamics for prediction and evaluation phases of the signal processing.

neuroscience↗

bioRxiv2024

Regulation of REM Sleep Onset and Homeostasis by Preoptic Glutamatergic Neurons

The preoptic area of the hypothalamus is key for the control of sleep onset and sleep homeostasis. Although traditionally considered exclusively somnogenic, recent studies identified a group of preoptic glutamatergic neurons that promote wakefulness. Specifically, our previous investigations demonstrated that chemogenetic stimulation of glutamatergic neurons within the medial-lateral preoptic area (MLPO_VGLUT2) promotes wakefulness, fragments non-rapid eye movement sleep (NREMs), and suppresses REM sleep (REMs). This evidence is further supported by recent work showing that preoptic glutamatergic neurons are activated during microarousals that fragment sleep in response to stress, and optogenetic stimulation of these neurons promotes microarousals and wakefulness. Thus, while the wake-promoting function of MLPO_VGLUT2 is clear, their role in sleep homeostasis has not been assessed. We tested the hypothesis that MLPO_VGLUT2 are wake-active, and their activation will increase wakefulness and disrupt sleep homeostasis via projections to arousal-promoting systems. Using fiber photometry, we found that MLPO_VGLUT2 were highly active during REMs, wakefulness and brief arousals, and remained minimally active during NREMs. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REMs onset and suppressed the REMs homeostatic response after total sleep deprivation. Chemogenetic inhibition of MLPO_VGLUT2 increased REMs time (during the light phase only) but did not influence REMs and NREMs homeostasis. Anterograde projection mapping revealed that MLPO_VGLUT2 innervate central regions that promote wakefulness and inhibit REMs. We conclude that MLPO_VGLUT2 powerfully suppress REMs and that exogenous --and possibly pathologic-- activation of these neurons disrupts REMs recovery, presumably by directly or indirectly activating REMs-inhibitory mechanisms. SIGNIFICANCE STATEMENTThe preoptic area of the hypothalamus has been extensively studied and its role in sleep regulation is well-established. Importantly, recent work identified a group of preoptic glutamatergic neurons (MLPO_VGLUT2) that are wake-active and promote wakefulness. However, whether these neurons influence sleep homeostasis remains unknown. We demonstrate that MLPO_VGLUT2 are maximally active during REM sleep (REMs), wakefulness and brief arousals from sleep, and innervate wake-promoting and REMs-inhibitory regions. MLPO_VGLUT2 stimulation inhibits REMs and REMs rebound after sleep deprivation, whereas their inactivation increases REMs but does not alter REMs homeostatic response. We thus identified a preoptic mechanism that powerfully suppresses REMs, which we propose may engage during normal sleep-to-wake transitions to block REMs intrusions into subsequent wakefulness.

neuroscience↗

bioRxiv2024

Interpersonal Synchronization in Mother-Child Dyads: Neural and Motor Coupling as a Mechanism for Motor Learning and Development in Preschoolers

Interpersonal movement synchrony (IMS) and brain-to-brain coupling play a crucial role in social behavior across species. In humans, IMS is often studied in structured tasks that require specific body movements, while spontaneous, unstructured movements have received less attention. In this study, we investigated both structured and spontaneous motor coordination in mother-child dyads. We recorded upper-body kinematics and dual-EEG from mothers and their preschool children during motor tasks and spontaneous face-to-face interactions. Our findings show that mother-child dyads synchronize their movements and neural activity, particularly in gamma band oscillations. This motor and neural synchrony evolves across task repetitions, with a strong correlation between motor and neural measures. Further, we observed that only motor synchronization was significantly related to the childs motor development stage, as assessed by the Movement Assessment Battery for Children. These results suggest that gamma band brain-to-brain coupling reflects joint motor coordination and mutual adaptation shaped by structured tasks and spontaneous interpersonal interactions.

neuroscience↗

bioRxiv2024

Effect of pre-germination temperature conditions on germination characteristics of temperate grassland species

Germination characteristics of target species used for grassland restoration are often unknown, despite such information would be essential for designing restoration interventions. Filling this knowledge gap and improving our understanding about germination responses of grassland species to varying cold and warm treatments could be especially important in the face of climate change. Here we studied the effect of three different durations of warm dry stratification and three different durations of cold wet stratification, and their combinations in a full factorial design (in total 15 different pre-germination treatments), on the germination capacity of 48 grassland species native to Central Europe. Stratification treatments modelled present and forecasted summer (1-3 months warm period) and winter (1-3 months cold period) temperature conditions, while the study of the combined effect of these treatments is especially important in spring-germinating species. As response variables, we calculated relative response indexes and germination uncertainties of each species separately and applied general linear models to study the effect of treatments on these variables. We found clear effect of warm- or cold stratification on relative response indexes only in four species: strong positive response to warm stratification was found in Silene conica, while strong positive response to cold stratification was found in Agrimonia eupatoria, Echium vulgare, and Plantago lanceolata. The responses to treatment combinations were contradictory or lacked clear trends in most of the species. Germination uncertainty in general was high for all species, supporting the fact that Central European grassland species often rely on bet hedging as risk spreading strategy, to avoid unfavourable conditions during seedling establishment.

plant biology↗

bioRxiv2024

Threat-Related Corticocortical Connectivity Elicited by Rapid Auditory Looms

While sounds of approaching objects are generally more salient than those of receding ones, the traditional association of this auditory looming bias with threat perception is subject to debate. Differences between looming and receding sounds may also be learned through non-threatening multisensory information, or influenced by confounding stimulus characteristics. To investigate, we analyzed corticocortical connectivity patterns from electroencephalography, examining the preferential processing of looming sounds under different attentional states. To simulate rapid distance changes we used complementary distance cues, previously studied in the looming bias literature. Notably, despite the absence of conscious threat perception, we observed crucial involvement of frontal cortical regions typically associated with threat and fear responses. Our findings suggest an underlying bias towards the ventral what stream over the dorsal where stream in auditory information processing, even when the participants task was solely focused on the discrimination of movement direction. These results support the idea, that the perceptual bias towards looming sounds reflects an auditory threat detection mechanism, while offering insights into the neural function involved in processing ecologically relevant environmental cues.

neuroscience↗

bioRxiv2024

Endocannabinoid biomarkers of vulnerability to the development of trauma-induced generalized fear responses

Traumatic experiences result in the development of posttraumatic stress disorder (PTSD) in 10-25% of exposed individuals. While human clinical studies suggest that susceptibility is potentially linked to endocannabinoid (eCB) signaling, neurobiological PTSD susceptibility factors are poorly understood. Employing a rat model of PTSD, we characterized distinct resilient and susceptible subpopulations based on generalized fear, a core symptom of PTSD. In these groups, we assessed i.) eCB levels by mass spectrometry and expression variations of eCB system- and iii.) neuroplasticity-related genes by real-time quantitative PCR in the circuitry relevant in trauma-induced changes. Furthermore, employing supervised and semi-supervised machine learning based statistical analytical models, we assessed iv.) gene expression patterns with the most robust predictive power regarding PTSD susceptibility. According to our findings, in our model, generalized fear responses occurred with sufficient variability to characterize distinct resilient and susceptible subpopulations. Susceptible subjects showed lower prelimbic and higher ventral hippocampal levels of eCB 2-arachidonoyl-glycerol (2-AG) compared to resilient subjects. Ventral hippocampal 2-AG content positively correlated with the strength of fear generalization. Furthermore, susceptibility was associated with i.) neuronal prefrontal, hippocampal and amygdalar hypoactivity, ii.) marked decrease in the expression of genes of transcription factors modulating neuroplasticity and iii.) an altered expression pattern of eCB-related genes, including enzymes involved in eCB metabolism. Unsupervised and semi-supervised statistical approaches highlighted that hippocampal gene expression patterns possess strong predictive power regarding susceptibility. Taken together, the marked eCB and neuroplasticity changes in susceptible individuals associated with abnormal activity patterns in the fear circuitry possibly contribute to context coding deficits, resulting in generalized fear. HighlightsO_LIWe assessed endocannabinoid and neuroplasticity correlates of PTSD susceptibility C_LIO_LIPosttrauma generalized fear strength separates susceptible and resilient individuals C_LIO_LISusceptible individuals show altered endocannabinoid levels in the fear circuitry C_LIO_LINeuroplasticity and endocannabinoid gene expression patterns predict susceptibility C_LI

neuroscience↗

bioRxiv2024

Devaluing memories of reward: A case for dopamine

We describe a novel role for dopamine in devaluing sensory memories of reward. Mesencephalic dopamine cells activated during a mediated devaluation phase were later chemogenetically reactivated. This retrieval of the devalued reward memory elicited a reduction in the hedonic evaluation of sucrose reward. Through optogenetic and chemogenetic manipulations, we confirm dopamine cells are both sufficient and necessary for mediated devaluation, and retrieval of these memories reflected dopamine release in the nucleus accumbens. Consistent with our computational modelling data, our findings indicate a critical role for dopamine in encoding predictive representations of the sensory features of reinforcement. Overall, we illuminate the elaborate nature of reinforcement signals encoded by dopamine and suggest novel approaches to treating a host of psychobiological disorders.

neuroscience↗

bioRxiv2023

Longitudinal study of functional brain networks for processing infant directed and adult directed speech during the first year

In most cultures infant directed speech (IDS) is used to communicate with young children. The main role IDS plays in parent-child interactions appears to change over time from conveying emotion to facilitating language acquisition. There is EEG evidence for the discrimination of IDS form adult directed speech (ADS) at birth, however, less is known about the development of brain networks responsible for differentially processing IDS and ADS. The current study compared topological characteristics of functional brain networks obtained from 49 healthy infants at the age of 0, 6, and 9 months listening to the same fairy tale presented by the same speaker in IDS and ADS speech. Brain connectivity was assessed by the phase lag synchronization index in 6 frequency bands (delta, theta, low alpha, high alpha, beta, gamma). The topology of the large scale network organization was quantified using minimum spanning tree graphs, separately for each band. The delta band cortical networks organization was found to be significantly more hierarchical and had a more cost-efficient organization during listening to ID compared to listening to AD. This network organization changes with age as nodes over the frontal cortex become more central within the network. The general picture emerging from the results is that with development the speech processing network becomes more integrated and its focus is shifting towards the left hemisphere. Our results suggest that ID speech specific differences in network topology are related to changes in the role of IDS during the first year of life. Highlights- Multiple stages of maturation are reflected by different EEG bands, occurring in parallel, but with different timing. - Networks processing infant directed speech changes during the first year of life reflecting the change in the role infant directed speech plays in development. - Speech processing networks are shifting towards the left hemisphere with age. - Longitudinal study of speech perception using functional networks on a large sample

neuroscience↗

bioRxiv2023

Early maturation of sound duration processing in the infant brain

The ability to process sound duration is crucial already at a very early age for laying the foundation for the main functions of auditory perception, such as object perception and music and language acquisition. With the availability of age-appropriate structural anatomical templates, we can reconstruct EEG source activity with much-improved reliability. The current study capitalized on this possibility by reconstructing the sources of event-related potential (ERP) waveforms sensitive to sound duration in four- and nine-month-old infants. Infants were presented with short (200 ms) and long (300 ms) sounds equiprobably delivered in random order. Two temporally separate ERP waveforms were found to be modulated by sound duration. Generators of these waveforms were mainly located in primary and secondary auditory area and other language-related regions, such as the superior temporal and the inferior frontal gyri. The results show marked developmental changes between four and nine months, partly reflected by scalp-recorded ERPs, but appearing in the underlying generators in a far more nuanced way. The results also confirm the feasibility of the application of anatomical templates in developmental populations.

neuroscience↗

bioRxiv2023

The effects of aging and hearing impairment on listening in noise

Listening in a noisy environment (e.g., speech in noise) relies on the fundamental ability to extract coherence from the variable sensory input. This allows the detection active sound sources and their segregation of them from the rest of the scene (figure-ground segregation). Peripheral and central causes of age-related decline of listening in noise were assessed by a tone-cloud-based figure detection task. In two conditions differing in the amount of noise, figure detection performance was equalized between young, normal-hearing, and hearing-impaired elderly listeners by adapting the stimulation separately to the abilities of each person. Based on behavioral measures and event-related brain potentials (ERP), in the absence of cognitive deficits, aging alone does not appear to significantly deteriorate the ability to detect sound sources in noise, although ERPs show delayed perceptual processes and some expected deterioration in attention and/or executive functions. However, even mild hearing impairment substantially reduces the ability to segregate individual sound sources within a complex auditory scene, and susceptibility to masking noise increases together with the severity of the hearing deficit. Significance StatementThis work provides new information about the contributions of central and peripheral causes to the typical age-related decline of listening in a noisy environment. Behavioral and neurophysiological data collected in a well-controlled model of listening in noise suggest that aging alone does not significantly reduce the ability to detect sound sources in a complex auditory scene. However, even mild hearing impairment significantly reduces this ability. The stimulus paradigm used appears to be quite sensitive to hearing loss, making it potentially useful for the early detection of hearing problems.

neuroscience↗

bioRxiv2022

Benefits of individualized brain anatomies and EEG electrode positions for auditory cortex localization

Due to its high temporal resolution and non-invasive nature, electroencephalography (EEG) is considered a method of great value for the field of auditory cognitive neuroscience. In performing source space analyses, localization accuracy poses a bottleneck, which precise forward models based on individualized attributes such as subject anatomy or electrode locations aim to overcome. Yet acquiring anatomical images or localizing EEG electrodes requires significant additional funds and processing time, making it an oftentimes inaccessible asset. Neuroscientific software offers template solutions, on which analyses can be based. For localizing the source of auditory evoked responses, we here compared the results of employing such template anatomies and electrode positions versus the subject-specific ones, as well as combinations of the two. All considered cases represented approaches commonly used in electrophysiological studies. We considered differences between two commonly used inverse solutions (dSPM, sLORETA) and targeted the primary auditory cortex; a notoriously small cortical region that is located within the lateral sulcus, thus more prone to errors in localization. Through systematical comparison of the outcomes in terms of auditory activity attributes and leakage quantification, we assessed how the individualization steps impacted the analyses outcomes. Both electrode locations as well as subject anatomies were found to have an effect, which though varied based on the configuration considered. When comparing the inverse solutions, we moreover found that dSPM more consistently benefited from individualization of subject characteristics. Based on the scientific question considered, our results may be used to facilitate the planning of auditory neuroscientific experiments in terms of expected infrastructure, personnel and funds.

neuroscience↗

bioRxiv2022

Speech prosody supports speaker selection and auditory stream segregation in a multi-talker situation

To process speech in a multi-talker environment, listeners need to segregate the mixture of incoming speech streams and focus their attention on one of them. Potentially, speech prosody could aid the segregation of different speakers, the selection of the desired speech stream, and detecting targets within the attended stream. For testing these issues, we recorded behavioral responses and extracted event-related potentials and functional brain networks from electroencephalographic signals recorded while participants listened to two concurrent speech streams, performing a lexical detection and a recognition memory task in parallel. Prosody manipulation was applied to the attended speech stream in one group of participants and to the ignored speech stream in another group. Naturally recorded speech stimuli were either intact, synthetically F0-flattened, or suppressed by the speaker. Results show that prosody - especially the parsing cues mediated by speech rate - facilitates stream selection, while playing a smaller role in auditory stream segmentation and target detection.

neuroscience↗