Biology subjects

Kelemen, E.

Publications and source records attributed to Kelemen, E..

4 recordsLinked to original sources

bioRxiv2026

Partial lesions of hypocretin neurons of the rat lateral hypothalamus affect wake and sleep regulation under increased sleep pressure

Hypocretin(orexin)-producing neurons in the lateral hypothalamic area are important for sleep and wake regulation in mammals and their damage in humans manifests clinically as narcolepsy. While in previous studies experimentally induced massive loss of these neurons revealed their physiological importance, small lesions and their manifestations can uncover more subtle features of sleep regulation and help understand the delicate processes in early stages of pathogenesis of narcolepsy. We studied the effects of partial lesions (approximately 30%) of hypocretin producing neurons in the lateral hypothalamus on sleep patterns and EEG in rats. The lesions did not change the normal sleep and wake pattern in undisturbed rats. The effects of lesions manifested under increased sleep pressure after six hours of sleep deprivation, when they led to accelerated dynamics of compensatory slow wave sleep. The lesions also led to a slight decrease in theta frequency in wakefulness and in REM sleep, which we observed during undisturbed sleep and wake behavior as well as after sleep deprivation.

neuroscience↗

bioRxiv2026

Behavioral and neuronal dynamics in a rat model of obsessive-compulsive disorder

While cognitive and behavioral manifestations of obsessive-compulsive disorder (OCD) are well known, the neuronal dynamics underlying these symptoms remain poorly understood. Theoretical work suggests that changes in the attractor dynamics of neuronal networks towards increased stability and decreased flexibility might cause behavioral and cognitive symptoms of OCD. We used chronic treatment with the D2 and D3 dopamine receptor agonist quinpirole as a rat model of the disease. In this model, we examined changes in behavioral dynamics and, in a parallel experiment, changes in organization of neuronal activity in the hippocampus and anterior cingulate cortex (ACC). At the behavioral level, we observed increased locomotion and repetitive stereotypical trajectories in quinpirole-treated rats, with frequency of repetitions increasing over the course of the session. At the level of neuronal activity, a gradual increase in the firing rate of ACC neurons within a session paralleled the dynamics of behavioral stereotypy after quinpirole treatment. In quinpirole-treated rats, we observed increased stability in the temporal organization of hippocampal neuronal firing, but no increase in the stability of the spatial organization of discharge. The increased stability of hippocampal firing was observed at both the level of single neurons and coordinated activity of neuronal pairs, and was connected to modulation of activity by theta rhythm. Studying neuronal activity changes underlying behavioral and cognitive manifestations of brain disorders is crucial for understanding and treating brain pathologies. HIGHLIGHTSO_LIDynamics of behavior and neuronal activity was characterized in rats after chronic quinpirole treatment, which is considered a model of obsessive-compulsive disorder. C_LIO_LIThe quinpirole treatment led to repetitive stereotypical trajectories, with increasing frequency of repetitions over the course of a session. C_LIO_LIThe quinpirole treatment was associated with more stable theta modulation of single-cell hippocampal firing within experimental sessions. C_LIO_LIQuinpirole increased stability in cell-pair correlations of hippocampal units within and between sessions. C_LIO_LIQuinpirole led to more stable coordination of local field potential activity between the hippocampus and anterior cingulate cortex at theta frequencies. C_LI

neuroscience↗

bioRxiv2021

Effects of intra-hippocampal corticosterone and sleep on consolidation of complex memory of aversive experience in rats

Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake state and high intra-hippocampal corticosterone on consolidation of aversive contextual memories as well as consolidation of association between simple trauma-related cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a "safe box" and then trained in fear conditioning paradigm in a distinct "shock box" with a prominent simple auditory cue serving as a phasic background cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1l) or corticosterone (10ng in 1l saline) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory test twenty-four hours later revealed that the saline-injected animals with sleep during consolidation had significantly stronger freezing response in the shock box compared to the safe box as well as increased freezing in response to the tone. Lack of post-learning sleep in saline injected animals led to generalization of fear response to the safe context, while association between simple cue and fear response was preserved. High intra-hippocampal corticosterone level during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to single stimulus was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable complex memories for a traumatic episode and distinct behavioral outcomes. HighlightsO_LIWe studied effect of sleep and intrahippocampal corticosterone on consolidation of memories surrounding stressful event modeled by fear conditioning in rats. C_LIO_LISleep following traumatic fear conditioning event is important for subsequent manifestation of fear response (freezing) specifically in the context of traumatic event but not in a neutral safe context. C_LIO_LILack of sleep or high intra-hippocampal corticosterone level during memory consolidation leads to generalization of fear response to both the traumatic and safe context. C_LIO_LIIncreased freezing in response to a trauma-related auditory cue was observed in saline injected rats regardless of wake/sleep state during consolidation. C_LIO_LIPost-learning intra-hippocampal corticosterone injection blocked response to a trauma-related auditory cue regardless of wake/sleep state during consolidation. C_LI

neuroscience↗

bioRxiv2017

Phencyclidine discoordinates hippocampal network activity but not place fields

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships between cognitive behavior, coordinated neural network function and information processing within the hippocampus place cell system. We report in rats that PCP (5mg/kg i.p.) impairs a well-learned hippocampus-dependent place avoidance behavior in rats that requires cognitive control, even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium and slow gamma oscillations in CA1 local field potentials (LFP) such that medium gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP but the drug discoordinates the sub-second temporal organization of discharge amongst place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations, despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the sub-second timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as the root of PCP-induced cognitive impairment.\n\nSIGNIFICANCE STATEMENTHippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the local field potential, and the discharge of a subset of pyramidal neurons called \"place cells\" is spatially organized such that discharge is restricted to locations called a cells \"place field.\" Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge, without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.

neuroscience↗