Biology subjects

Hegedus, P.

Publications and source records attributed to Hegedus, P..

6 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↗

bioRxiv2023

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system. While they have a well-documented role in the regulation of sleep-wake states, whether and how BFPVNs participate in mediating awake behaviors is not known. To address this, we performed bulk calcium imaging and recorded single neuronal activity from the horizontal band of the diagonal band of Broca (HDB) while mice were performing an associative learning task. Genetically identified BFPVNs of the HDB responded with a distinctive, phasic activation to punishment. In contrast, reward only elicited slow and delayed responses, while stimuli predicting behavioral reinforcement (reward or punishment) were followed by a gradual increase of HDB BFPVN firing rates. Optogenetic inhibition of HDB BFPVNs during punishment impaired the formation of cue-outcome associations, suggesting a causal role of these neurons in associative learning. Mapping the input-output connectivity of HDB BFPVNs by anterograde and mono-transsynaptic retrograde tracing experiments showed that these neurons received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key structures of the limbic system including the medial septum, the retrosplenial cortex and the hippocampus. Bulk calcium imaging performed in these termination regions indicated that HDB BFPVNs broadcast information about aversive stimuli to multiple downstream targets. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions during awake behaviors.

neuroscience↗

bioRxiv2023

Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

Studying animal models furthers our understanding of Parkinsons disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinsons disease in mice. Highlights- Unilateral striatal 6-OHDA injection caused an early onset dose-dependent behavioral deficit in mice - Behavioral deficit manifested as mild impairment of locomotion and locomotive movement initialization - Behavioral changes were accompanied by moderate, dose-dependent loss of SNc dopaminergic neurons - Behavioral changes were paralleled by ultrastructural alterations of SNc dopaminergic neurons

neuroscience↗

bioRxiv2020

Non-bursting non-rhythmic neurons of the ventral pallidum form cell assemblies and respond to reward and punishment during Pavlovian conditioning

The ventral pallidum (VP) is a major hub interfacing striatopallidal and limbic circuits, conveying information about salience and valence crucial to adjusting behavior. However, how neuron populations of the VP with different firing properties represent these variables is not fully understood. Therefore, we trained mice on auditory Pavlovian conditioning and recorded the activity of VP neurons while mice were performing the task. Many VP neurons responded to punishment (51%) and reward (44%), either by firing rate increase or decrease. Additionally, 20% of cells responded to outcome-predicting auditory stimuli, showing larger responses to reward-predicting cues compared to those that signaled likely punishment. We found that a large subset of VP neurons showed burst firing based on their auto-correlograms, while a small population exhibited fast rhythmic discharge in the beta/gamma frequency range. Some bursting neurons exhibited distinct response properties of their bursts and single spikes, suggesting a multiplexed coding scheme in the VP. However, non-bursting, non-rhythmic neurons were the most sensitive to reward and punishment. Finally, we demonstrate the presence of synchronously firing neuron assemblies in the VP. Neurons participating in such assemblies were particularly responsive to reinforcing stimuli. This suggests that a synchronous, non-bursting, non-rhythmic neuron population of the VP is responsible for the lions share of ventral pallidal salience representation, likely important for reinforcement learning. Significance statementThe ventral pallidum (VP) is a subcortical brain area that participates in regulating motion and emotion by processing information related to appetitive and aversive stimuli. However, how these stimuli are represented by VP neural circuits is not well understood. Therefore, we investigated how VP neuron populations defined by their firing properties respond to reward and punishment during Pavlovian conditioning. We found that a distinct, non-bursting-non-rhythmic group of neurons was responsible for most responses to reward and punishment in the VP. Neurons of this group formed co-active cell assemblies and multiplexed different types of information via different firing patterns, revealing flexible and plastic neuronal representation strategies in the VP during associative learning.

neuroscience↗

bioRxiv2019

OPETH: Open Source Solution for Real-time Peri-event Time Histogram Based on Open Ephys

Single cell electrophysiology remains one of the most widely used approaches of systems neuroscience. Real-time feedback during electrophysiology experiments is important to guide experimental decisions that eventually determine the quality of recording, duration of the project and value of the collected data. We present an open-source tool that enables flexible online visualization of action potential alignment to external events, called the peri-event or peristimulus time histogram (OPETH). Based on the Open Ephys open source data acquisition system, we developed a Python interface for real-time plotting of neuronal spike times and evoked waveforms with respect to external events represented by digital logic signals. These digital inputs may signal photostimulation time stamps for in vivo optogenetic identification of cell types or the times of behaviorally relevant events during in vivo behavioral neurophysiology experiments. Therefore, OPETH allows real-time identification of genetically defined neuron types or behaviorally responsive populations. By allowing hunting for neurons of interest, OPETH may significantly increase the efficiency of experiments that combine in vivo electrophysiology with behavior or optogenetic tagging of neurons.

neuroscience↗

bioRxiv2018

Open source toolkit for temporally controlled rodent behavior suitable for electrophysiology and optogenetic manipulations

Understanding how the brain controls behavior requires observing and manipulating neural activity in awake behaving animals. Neuronal firing is timed at millisecond precision. Therefore, to decipher temporal coding, it is necessary to monitor and control animal behavior at the same level of temporal accuracy. However, it is technically challenging to deliver sensory stimuli and reinforcers as well as to read the behavioral responses they elicit with millisecond precision. Presently available commercial systems often excel in specific aspects of behavior control, but they do not provide a customizable environment allowing flexible experimental design while maintaining high standards for temporal control necessary for interpreting neuronal activity. Moreover, delay measurements of stimulus and reinforcement delivery are largely unavailable. We combined microcontroller-based behavior control with a sound delivery system for playing complex acoustic stimuli, fast solenoid valves for precisely timed reinforcement delivery and a custom-built sound attenuated chamber using high-end industrial insulation materials. Together this setup provides a physical environment to train head-fixed animals, enables calibrated sound stimuli and precisely timed fluid and air puff presentation as reinforcers. We provide latency measurements for stimulus and reinforcement delivery and an algorithm to perform such measurements on other behavior control systems. Combined with electrophysiology and optogenetic manipulations, the millisecond timing accuracy will help interpret temporally precise neural signals and behavioral changes. Additionally, since software and hardware provided here can be readily customized to achieve a large variety of paradigms, these solutions enable an unusually flexible design of rodent behavioral experiments.

neuroscience↗