Biology subjects

Kiraly, B.

Publications and source records attributed to Kiraly, B..

8 recordsLinked to original sources

bioRxiv2026

Hippocampo-septal inhibitory feedback controls the medial septal circuit as a function of brain state, pyramidal cell activity and movement speed.

Encoding novel experiences and retrieving stored information rely on the hippocampal theta rhythm in several mammalian species. Coordination of putative pacemakers in the medial septum (MS) by the GABAergic hippocampo-septal (HS) feedback is hypothesized to be essential for theta genesis. In order to reveal how the HS-feedback controls the MS circuit, and through it hippocampal oscillations in general, we set out to uncover the behavior-related activity of HS neurons as well as how different components of the MS network are regulated by the HS-feedback. Utilizing computational modelling and in vivo optogenetic manipulation of the HS pathway, we show that the HS feedback is not required for theta generation, which is primarily governed by intra-MS connections. HS blockade did not alter the phase coupling of MS neurons to hippocampal theta rhythm nor the synchrony between rhythmic MS neurons but augmented ongoing theta and coupled mid-gamma oscillations in the hippocampus. By contrast, correlated activity between non-rhythmic MS neurons was sensitive to HS blockade. Moreover, the HS feedback scaled with hippocampal activity and running speed. In turn, modulation of MS neurons by running and ripples was diminished by the transient suppression of HS terminals. These findings suggest that the HS feedback exerts inhibitory control of the MS depending upon hippocampal output and movement speed.

neuroscience↗

bioRxiv2026

Cholinergic--dopaminergic interplay underlies prediction error broadcasting

Neuromodulatory systems, notably basal forebrain cholinergic and midbrain dopaminergic pathways, critically influence reinforcement learning 1-3. However, whether and how they cooperate or compete to jointly control associative learning functions remains unresolved. Here we demonstrate that basal forebrain cholinergic and midbrain dopaminergic projection systems form a coordinated and cross-regulating architecture for encoding prediction errors. Using dual-cell-type optogenetic tagging and real-time neurotransmitter measurements in mice performing a psychometric operant learning task, we simultaneously monitored cholinergic and dopaminergic activity during learning. Dopamine and acetylcholine jointly encoded reward prediction errors synergistically following reward and reward-predicting stimuli. In contrast, aversive outcomes elicited opposite responses in cholinergic neurons and approximately half of dopaminergic neurons. Activity in these two populations exhibited negative trial-by-trial correlations, revealing antagonistic dynamics. Consistently, channelrhodopsin-assisted circuit mapping uncovered a disynaptic inhibitory pathway from cholinergic to dopaminergic neurons. Chemogenetic suppression of cholinergic activity disrupted dopaminergic prediction error signaling, reduced punishment-induced suppression of dopamine release, and impaired learning. These results demonstrate that prediction error signaling is jointly implemented by coordinated interactions between major neuromodulatory systems, challenging the prevailing view of their functional independence and revealing coordinated cross-system interactions as an organizing principle of reinforcement learning, with implications for neuropsychiatric disease 4-6.

neuroscience↗

bioRxiv2025

Face photo-based age acceleration predicts all-cause mortality and differs among occupations

While scientists argue what aging is and what drives aging, it is widely accepted that our face changes drastically with age and that mortality increases in late life. We hypothesize that people of the same age can be biologically older than others and that the human face may reflect accelerated molecular aging. To test this hypothesis we examine the associations of face photo-based age acceleration with mortality and lifestyle. For this purpose, we trained and tested artificial intelligence models on 442,110 photos of famous people. We found that face photo-based age predicts all-cause mortality for middle-aged and older individuals meaning that those age faster based on their face photo die sooner. We also found that, based on face photos, sport is the slowest aging occupation among famous people consistently to previous findings showing the benefits of exercise to epigenetic aging. Overall, we demonstrate that the face photo-base age model approaches biological age in some extent and provides a low-cost and fast complementary measurement for personalized medicine, as well as aging and rejuvenation studies. The model is available for demonstration and academic research purposes at https://photoage.sztaki.hu/.

bioinformatics↗

bioRxiv2025

Most ventral pallidal cholinergic neurons are cortically projecting bursting basal forebrain cholinergic neurons

The ventral pallidum (VP) lies at the intersection of basal ganglia and basal forebrain circuitry, possessing attributes of both major subcortical systems. Basal forebrain cholinergic neurons are rapidly recruited by reinforcement feedback and project to cortical and subcortical forebrain targets; in contrast, striatal cholinergic cells are local interneurons exhibiting classical pause-burst responses to rewards. However, VP cholinergic neurons (VPCNs) are less characterized, and it is unclear whether basal forebrain and striatal type cholinergic neurons mix in the VP. Therefore, we performed anterograde and mono-transsynaptic retrograde labeling, in vitro acute slice recordings and bulk calcium recordings of VPCNs. We found that VPCNs broadly interact with the affective circuitry that processes rewards and punishments, targeting the basolateral amygdala, the nucleus accumbens, the medial prefrontal cortex and the lateral habenula, while receiving inputs from the nucleus accumbens, hypothalamus, central amygdala, bed nucleus of stria terminalis and the ventral tegmental area. Bulk calcium recordings revealed VPCN responses to rewards, punishments and reward-predicting cues, like those of the horizontal diagonal band of Broca of the basal forebrain. Acute slice recordings showed that most VPCNs resembled the bursting type of basal forebrain cholinergic neurons (BFCNs), while a few of them were of the regular rhythmic type, which sharply differentiated most VPCNs from striatal cholinergic interneurons. These results were confirmed by in vivo electrophysiological recordings of putative VPCNs largely resembling bursting BFCNs. We conclude that most VPCNs are BFCNs with specialized connectivity to relay aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction.

neuroscience↗

bioRxiv2023

Altered reactivity to threatening stimuli in Drosophila models of Parkinson's disease, revealed by a trial-based assay

The fruit fly Drosophila melanogaster emerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic, circuit-level and behavioral differences hinder the interpretability of fruit fly models for human disease. Therefore, to allow a more direct fly-versus-human comparison, we surveyed the rarely exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinsons disease (PD), including overexpression of human mutant Parkin or -synuclein proteins and mutations in dopamine receptors. Flies with different genetic backgrounds displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. We also found age-dependent trends in behavioral choice during the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of genetic Drosophila models of neurodegeneration, taking us one step closer to bridging the gap in fly-to-human translation.

neuroscience↗

bioRxiv2023

Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced maladaptive behavior

ABSTRACTTraumatic events can immediately lead to debilitating symptoms collectively called Acute Stress Disorder (ASD), however the mechanisms of ASD are poorly understood. Using a rodent model of ASD here we identify a crucial communication bottleneck between the brainstem and the forebrain, the calretinin-positive neurons in the paraventricular thalamus (PVT/CR+), that controls ASD. We show that following a single acute stress event, the pre-sleep behavior of the mice is altered for several days in parallel with a persistent increase in the firing rate of PVT/CR+ cells. Optogenetic inhibition of PVT/CR+ neuronal activity after the stress event for one hour was sufficient to rescue both the ASD symptoms and the prolonged increase in PVT/CR+ firing rate. Inhibition applied 5 days later was still able to ameliorate some of the symptoms. These data suggest that post-stress activity of PVT/CR+ neurons play a critical role in mediating the acute forms of stress-related affective dysfunctions. One-Sentence SummaryPost-stress inhibition of paraventricular thalamic neurons prevents the emergence of acute stressed phenotype.

neuroscience↗

bioRxiv2022

Cholinergic neuronal responses to probabilistic outcome-predicting stimuli follow a weighed, unsigned prediction error model and anticipate behavioral responses

Basal forebrain cholinergic neurons (BFCNs) play an important role in associative learning, suggesting that BFCNs may participate in processing sensory stimuli that predict future outcomes. However, little is known about how BFCNs respond to outcome-predictive sensory cues and the impact of outcome probabilities on BFCN responses has not been explored. Therefore, we performed bulk calcium imaging and recorded spiking output of identified cholinergic neurons from the basal forebrain of mice performing a probabilistic Pavlovian cued outcome task that allowed us to control the predictive strength of cue stimuli. BFCNs responded strongly to sensory cues predicting likely reward, while little response was observed for cues that were rarely paired with reward. Reward delivery led to the activation of BFCNs, with less expected rewards eliciting a stronger response, while air puff punishments also evoked positive-going responses from BFCNs. We propose that BFCNs differentially weigh predictions of positive and negative reinforcement, reflecting divergent relative salience of forecasting appetitive and aversive outcomes, in accordance with a simple reinforcement learning model of a weighed, unsigned prediction error. Finally, the extent of cholinergic activation after cue stimuli predicted subsequent decision speed, suggesting that the expectation-gated cholinergic firing is instructive to reward-seeking behaviors.

neuroscience↗

bioRxiv2020

In Vivo Localization of Deep Brain Implants in Mice

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges even for expert operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to the gold standard histological reconstruction. Adjustment of the recording depth with electrode microdrives or early termination of unsuccessful experiments saves many working hours, while fast 3-dimensional feedback helps surgeons to avoid systematic errors. Increased aiming precision will allow more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical layers.

neuroscience↗