Biology subjects

Kocsis, B.

Publications and source records attributed to Kocsis, B..

8 recordsLinked to original sources

bioRxiv2025

Altered network function in hippocampus after sub-chronic activation of Cannabis receptors in peri-adolescence

The Cannabinoid 1-receptor (CB1R) is found in particularly high levels in the hippocampus (HPC), increased CB1R density and binding observed in patients with schizophrenia, and epidemiological studies suggest that regular cannabis use during adolescence is a risk factor for the disease. Historically, concerns around adolescent marijuana use focused on the development of psychosis later in life, however recent findings indicate that cognitive domains may also be at risk. CB1R was shown to interfere with neuronal network oscillations and to impair sensory gating and memory function. Neuronal oscillations are essential in multiple cognitive functions and their impairment was documented in neurological and psychiatric diseases. The aim of this study was to investigate how adolescent pre-treatment with the CB1R selective agonist CP-55940 may lead to abnormalities in theta synchronization in adulthood. Rats were pre-treated with CP-55940 (n=11, 6 males, 5 females) or vehicle (n=8, 4 males, 4 females) during adolescence (daily i/p injections between PND 32-36 or PND 42-46, n=10 and 9, respectively). They were then tested in adulthood (PND 70-88, n=17 or PND 111-115, n=2) under urethane anesthesia. Hippocampal theta rhythm was elicited by brainstem stimulation at 5 intensity levels one hour before and up to 5 hours after injection. We found a lasting significant decrease in theta power after CP-55940 in adult rats which was aggravated further in rats pre-treated in adolescence with the CB1R agonist. The effect was significantly larger (p=0.0462) in rats pre-treated during early adolescence (PND 32-36) compared to the group pre-treated during late adolescence (PND 42-46). We conclude that 1. Exposure to cannabis during adolescence leads to increased sensitivity to CB1R agonist in adulthood; 2. Early adolescence, a critical period for development of HPC networks generating theta rhythm, is particularly prone to this sensitivity.

neuroscience↗

bioRxiv2024

CB-1 receptor agonist drastically changes oscillatory activity, defining active sleep

Brain oscillations in different behavioral states are essential for cognition, and oscillopathies contribute to cognitive dysfunction in neuro-psychiatric diseases. Cannabis-1 receptor (CB1-R) activation was reported to suppress theta and fast gamma activities in rats during waking exploration, and here, we show that cannabis fundamentally alters network activity during sleep, as well. Prominent theta rhythm is present in rapid eye movement sleep (REMS), whereas fast oscillations appear as regular sequences of sleep spindles during intermediate sleep (IS) - both implicated in dreaming and memory consolidation. The CB1-R agonist disrupted these mechanisms, restructuring IS-REMS episodes; IS lengthened 6-fold and intruded REMS, where on-going theta was drastically reduced. The spindle architecture was also affected; its amplitude increased, and its peak frequency down-shifted into the theta range. Cannabis is known to induce psychotic-like conditions and cognitive deficits; thus, our results may help understanding the dual effect of cannabis on cognitive states and the role of network oscillations in psychiatric pathology.

neuroscience↗

bioRxiv2022

Rhythmic firing of neurons in the medulla of conscious freely behaving rats: rhythmic coupling with baroreceptor input

Recent investigations emphasized the importance of neural control of cardiovascular adjustments in complex behaviors, including stress, exercise, arousal, sleep-wake states, and different tasks. Baroreceptor feedback is an essential component of this system acting on different time scales from maintaining stable levels of cardiovascular parameters on the long-term to rapid alterations according to behavior. The baroreceptor input is essentially rhythmic, reflecting periodic fluctuations in arterial blood pressure. Cardiac rhythm is a prominent feature of the autonomic control system, present on different levels, including neuron activity in central circuits. The mechanism of rhythmic entrainment of neuron firing by the baroreceptor input was studied in great detail under anesthesia but recordings of sympathetic-related neuron firing in freely moving animals remain extremely scarce. In this study we recorded multiple single neuron activity in the reticular formation of the medulla in freely moving rats during natural behavior. Neurons firing in synchrony with the cardiac rhythm were detected in each experiment (n=4). In agreement with prior observations in anesthetized cats, we found that neurons in this area exhibited high neuron-to-neuron variability and temporal flexibility in their coupling to cardiac rhythm in freely moving rats, as well. This included firing in bursts at multiples of cardiac cycles, but not directly coupled to the heartbeat, supporting the concept of baroreceptor input entraining intrinsic neural oscillations rather than imposing a rhythm of solely external origin on these networks. It may also point to a mechanism of maintaining the basic characteristics of sympathetic neuron activity, i.e. burst-discharge and cardiac-related rhythmicity, on the background of behavior-related adjustments in their firing rate.

neuroscience↗

bioRxiv2021

Respiratory coupling between prefrontal cortex and hippocampus of rats anesthetized with urethane in theta and non-theta states

Respiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artifacts, has been firmly established in recent years using a variety of advanced techniques. Respiratory related oscillation (RRO) is derived from rhythmic nasal airflow in the olfactory bulb (OB) and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states, it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep. The goal of this study was to test RRO synchronization between PFC and HC under urethane anesthesia where theta and non-theta states spontaneously alternate. We found that in theta states, PFC-HC coherences significantly correlated with OB-HC but not with OB-PFC, even though RRO was stronger in PFC than in HC. In non-theta states, PFC-HC synchrony correlated with coherences connecting OB to either PFC or HC. Thus, similar to freely behaving rats, PFC-HC synchrony at RRO was primarily dependent on the response of HC to the common rhythmic drive, but only in theta state. The findings help outlining the value and the limits of applications in which urethane-anesthetized rats can be used for modeling the neural mechanisms of RRO in behaving animals.

neuroscience↗

bioRxiv2021

Huygens synchronization of medial septal pacemaker neurons generates hippocampal theta oscillation

Episodic learning and memory retrieval are critically dependent on a hippocampal 4-12 Hz oscillatory clock signal, the theta oscillation. This clock is largely externally paced, by a network of GABAergic neurons in the medial septum (MS). Theoretical studies suggested a range of hypotheses how this network may achieve theta synchrony; however, experimental evidence is still lacking. By recording multiple single MS neurons and hippocampal local field potential oscillations simultaneously, with both acute and chronically implanted silicon probes, we show that MS pacemaker units oscillate at individual frequencies within the theta range in rodents. Synchronization of MS neuron frequencies, accompanied by an elevation of firing rates, was found to parallel hippocampal theta formation in multiple rodent model systems. This suggests a general mechanism for theta synchronization, akin to the synchronization of weakly coupled pendulum clocks observed by Huygens in the 17th century. We optogenetically identified the MS pacemaker units as parvalbumin-expressing GABAergic neurons, while the previously enigmatic MS glutamatergic neurons were mostly theta-activated non-rhythmic cells. Our data were consistent with a network model of partially connected single-compartment inhibitory pacemaker neurons, in which synchronization and de-synchronization in the frequency domain upon waxing and waning tonic excitatory drive was sufficient to toggle MS network output between theta and non-theta states. These results provide experimental and theoretical support to a frequency-synchronization mechanism for pacing hippocampal theta, which may serve as an inspirational prototype for the countless examples of synchronization processes in the central nervous system from Nematoda to Anthropoda to Chordate and Vertebrate phyla.

neuroscience↗

bioRxiv2020

Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb

An explosion of recent findings firmly demonstrated that brain activity and cognitive function in rodents and humans are modulated synchronously with nasal respiration. Rhythmic respiratory (RR) coupling of wide-spread forebrain activity was confirmed using advanced techniques, including current source density analysis, single unit firing, and phase modulation of local gamma activity, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) allowing dynamic PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate ([~]2 Hz) at rest, outside of the short sniffing bouts. We found strong and stable OB-PFC coherence, contrasting OB-HC coherence which was low but highly variable. PFC-HC coupling, however, primarily correlated with the latter, indicating that HC access to the PFC output is dynamically regulated by the responsiveness of HC to the common rhythmic drive. This pattern was present in both theta and non-theta states of waking, whereas PFC-HC communication appeared protected from RR synchronization in sleep states. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the OB epithelium due to infections, such as in COVID-19.

neuroscience↗

bioRxiv2018

Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC)

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency and the amplitude of a high-frequency component of local field potentials (LFP). Characterizing the relationship between nested oscillations in LFPs, PAC has become a powerful tool for understanding neural dynamics in both animals and humans. In this work, we introduce a new application for this measure to two LFPs to infer the direction and strength of rhythmic neural transmission between distinct networks. Based on recently accumulating evidence that transmembrane currents related to action potentials contribute a broad-band component to LFP in the high-gamma band, we hypothesized that PAC calculated between high-gamma in one LFP and low-frequency oscillations in another would relate the output (spiking) of one area to the input (soma/dendritic postsynaptic potentials) of the other. We tested this hypothesis on theta-band long range communications between hippocampus and prefrontal cortex (PFC) and theta-band short range communications between different regions within the hippocampus. The results were interpreted within the known anatomical connections predicting hippocampus[->]PFC and DG[->]CA3[->]CA1, i.e., theta transmission is unidirectional in both cases: from hippocampus to PFC and along the tri-synaptic pathway within hippocampus. We found that (1) hippocampal high-gamma amplitude was significantly coupled to theta phase in PFC, but not vice versa; (2) similarly, high-gamma amplitude in DG was significantly coupled to CA1 theta phase, but not vice versa, and (3) the DG high-gamma-CA1 theta PAC was significantly correlated with DG[->]CA1 Granger causality, a well-established analytical measure of directional neural transmission. These results support the hypothesis that inter-regional PAC (ir-PAC) can be used to relate the output of a \"driver\" network (i.e., high gamma) to the input of a \"receiver\" network (i.e., theta) and thereby establish the direction and strength of rhythmic neural transmission.

neuroscience↗

bioRxiv2017

Modeling the schizophrenias: subunit-specific NMDAR antagonism dissociates oscillatory signatures of frontal hypofunction and hippocampal hyperfunction

NMDAR antagonism alters mesolimbic, hippocampal, and cortical function, acutely reproducing the positive, cognitive, and negative symptoms of schizophrenia. These physiological and behavioral effects may depend differentially on NMDAR subtype-and region-specific effects. The dramatic electrophysiological signatures of NMDAR blockade in rodents include potentiated high frequency oscillations (HFOs, ~140 Hz), likely generated in mesolimbic structures, and increased HFO phase-amplitude coupling (PAC), a phenomenon related to goal-directed behavior and dopaminergic tone. This study examined the impact of subtype-specific NMDAR antagonism on HFOs and PAC. We found that positive-symptom-associated NR2A-preferring antagonism (NVP-AAM077), but not NR2B-specific antagonism (Ro25-6985) or saline control, replicated increases in HFO power seen with nonspecific antagonism (MK-801). However, PAC following NR2A-preferring antagonism was distinct from all other conditions. While{theta} -HFO PAC was prominent or potentiated in other conditions, NVP-AAM077 increased{delta} -HFO PAC and decreased{theta} -HFO PAC. Furthermore, active wake epochs exhibiting narrowband frontal{delta} oscillations, and not broadband sleep-associated{delta} , selectively exhibited{delta} -HFO coupling, while paradoxical sleep epochs having a high CA1{theta} to frontal{delta} ratio selectively exhibited{theta} -HFO coupling. Our results suggest: (1) NR2A-preferring antagonism induces oscillopathies re[fl]ecting frontal hyperfunction and hippocampal hypofunction; and (2) HFO PAC indexes cortical vs. hippocampal control of mesolimbic circuits.

neuroscience↗