The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.

• MeSH
• amfetamin farmakologie   MeSH
• amygdala fyziologie   MeSH
• hipokampus * fyziologie   MeSH
• konsolidace paměti * fyziologie   MeSH
• krysa rodu rattus MeSH
• mozek fyziologie   MeSH
• neurony fyziologie   metabolismus   MeSH
• nucleus accumbens * fyziologie   MeSH
• odměna * MeSH
• paměť fyziologie   MeSH
• podněty MeSH
• prefrontální mozková kůra fyziologie   MeSH
• rozpomínání * fyziologie   MeSH
• strojové učení MeSH
• tegmentum mesencephali - area ventralis * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

High-intensity interval training (HIIT) is considered an effective therapy strategy for improving chronic pain associated with osteoarthritis (OA). Perineuronal nets (PNNs) are specialized extracellular matrix structures in the cerebral cortex that play a crucial role in regulating chronic pain. However, little is unknown whether HIIT could alleviate OA pain sensitization by reducing PNN levels. This study aimed to determine whether HIIT could reduce sensitivity of the affected joint(s) to pain in a chronic pain model in rats with OA. A rat model of interest was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Thereafter, the mechanical withdrawal thresholds (MWTs) and PNN levels in the contralateral medial prefrontal cortex (mPFC) were measured in rats in the presence or absence of HIIT alone or in combination with injection of chondroitinase-ABC (ChABC) into the contralateral mPFC (inducing the degradation of PNNs), respectively. Results indicated that rats with OA exhibited significant reductions in MWTs, but a significant increase in the PNN levels; that HIIT reversed changes in MWTs and PNN levels in rats with OA, and that pretreatment of ChABC abolished effects of HIIT on MWTs, with PNN levels not changed. We concluded that pain sensitization in rats with OA may correlate with an increase in PNN levels in the mPFC, and that HIIT may increases OA pain-sensitive threshold by reduction of the PNN levels in the mPFC. Keywords: Osteoarthritis, Chronic pain, Pain sensitization, High-intensity interval training, Perineuronal nets.

• MeSH
• chronická bolest terapie   patofyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• kondiční příprava zvířat fyziologie   metody   MeSH
• krysa rodu rattus MeSH
• osteoartróza * terapie   MeSH
• potkani Sprague-Dawley * MeSH
• práh bolesti * MeSH
• prefrontální mozková kůra * metabolismus   MeSH
• vysoce intenzivní intervalový trénink * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.

• MeSH
• alkoholismus * farmakoterapie   patofyziologie   MeSH
• aminokyseliny MeSH
• bicyklické sloučeniny heterocyklické * farmakologie   MeSH
• biologické markery MeSH
• evokované potenciály účinky léků   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• prefrontální mozková kůra * účinky léků   patofyziologie   metabolismus   MeSH
• psilocybin * farmakologie   MeSH
• receptory metabotropního glutamátu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

• MeSH
• emoce MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek MeSH
• posttraumatická stresová porucha * psychologie   MeSH
• prefrontální mozková kůra MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A subpopulation of astrocytes on the brain's surface, known as subpial astrocytes, constitutes the "glia limitans superficialis" (GLS), which is an interface between the brain parenchyma and the cerebrospinal fluid (CSF) in the subpial space. Changes in connexin-43 (Cx43) and aquaporin-4 (AQP4) proteins in subpial astrocytes were examined in the medial prefrontal cortex at postoperative day 1, 3, 7, 14, and 21 after sham operation and sciatic nerve compression (SNC). In addition, we tested the altered uptake of TRITC-conjugated 3 kDa dextran by reactive subpial astrocytes. Cellular immunofluorescence (IF) detection and image analysis were used to examine changes in Cx43 and AQP4 protein levels, as well as TRITC-conjugated 3 kDa dextran, in subpial astrocytes. The intensity of Cx43-IF was significantly increased, but AQP4-IF decreased in subpial astrocytes of sham- and SNC-operated rats during all survival periods compared to naïve controls. Similarly, the uptake of 3 kDa dextran in the GLS was reduced following both sham and SNC operations. The results suggest that both sciatic nerve injury and peripheral tissue injury alone can induce changes in subpial astrocytes related to the spread of their reactivity across the cortical surface mediated by increased amounts of gap junctions. At the same time, water transport and solute uptake were impaired in subpial astrocytes.

• MeSH
• akvaporin 4 * metabolismus   MeSH
• astrocyty * metabolismus   MeSH
• dextrany * metabolismus   MeSH
• konexin 43 * metabolismus   MeSH
• krysa rodu rattus MeSH
• nervus ischiadicus * zranění   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• prefrontální mozková kůra * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Obsedantně-kompulzivní porucha (OCD) je zneschopňující psychiatrické onemocnění projevující se vtíravými myšlenkami a nutkavými úkony. Významná část pacientů s OCD je refrakterních k současným léčebným metodám a představují tak výzvu pro pochopení patofyziologických mechanismů OCD. Projekt si klade za cíl prozkoumat kauzální vztahy mezi symptomy OCD, strukturou a funkcí mozku. Na základě charakteristik symptomů OCD a neurozobrazovacích studií projekt postuluje OCD jako poruchu rozhodování spočívající v narušených funkcích ocenění a vyhodnocování pravděpodobnosti, zvýšené averzi ke ztrátám a riziku, nadměrné signalizaci chyb a snížené aktivaci klidové sítě. Neurální podklad narušeného rozhodování bude zkoumán pomocí humánních behaviorálních, elektrofyziologických a fMRI experimentů v kombinaci s 2 animálními modely OCD zahrnujícími rozhodovací úlohy, přímé nahrávání elektrické aktivity (tetrody) a molekulární imaging u potkanů. Cílem projektu je vytvoření translačního modelu OCD, umožňujícího identifikovat nové terapeutické cíle pro cílenou neurostimulaci a další léčebné modality.; Obsessive-compulsive disorder (OCD) is a disabling psychiatric condition characterized by intrusive thoughts and repetitive actions. A substantial part of OCD patients is refractory to current treatment which poses a challenge to the understanding of pathophysiological mechanisms of OCD. This project aims to explore the causal interactions between OCD symptoms, brain structure and function. On the basis of features of OCD symptoms and brain imaging studies, the project postulates OCD as a decision making (DM) disorder resting on altered valuation and probability weighing functions, inflated loss and risk aversion, increased error signalling, and diminished resting state network activity. The substrate of altered DM will be explored in behavioural, electrophysiological and fMRI DM experiments in humans, combined with 2 animal models of OCD including DM tasks, direct electrical recording (tetrodes) and molecular imaging in rats. The project aims at a translational model of OCD allowing to identify novel therapeutic targets for navigated neurostimulation and other treatment modalities.

• Klíčová slova
• Animal models, rozhodování, Obsessive-compulsive disorder, obsedantně-kompulzivní porucha, orbitofronální kůra, signalizace chyb, default mode network, decision making, orbitofrontal cortex, error signalling, default mode network, animální modely, modelování pomocí strukturálních rovnic (SEM), přímé nahrávání regionální elektrické aktivity (tetrody), molekulární zobrazení genů časné odpovědi, structural equation modelling (SEM), direct regional electrical activity recording (tetrodes), molecular imaging of immediate-early genes,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

BACKGROUND: Elevated brain levels of kynurenic acid (KYNA), a metabolite in the kynurenine pathway, are associated with cognitive dysfunctions, which are nowadays often considered as fundamental characteristics of several psychopathologies; however, the role of KYNA in mental illnesses, such as schizophrenia, is not fully elucidated. This study aimed to assess KYNA levels in the prefrontal cortex (PFC) of rats prenatally treated with methylazoxymethanol (MAM) acetate, i.e., a well-validated neurodevelopmental animal model of schizophrenia. The effects of an early pharmacological modulation of the endogenous cannabinoid system were also evaluated. METHODS: Pregnant Sprague-Dawley rats were treated with MAM (22 mg/kg, ip) or its vehicle at gestational day 17. Male offspring were treated with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day, ip) or with the typical antipsychotic haloperidol (0.6 mg/kg/day, ip) from postnatal day (PND) 19 to PND39. The locomotor activity and cognitive performance were assessed in the novel object recognition test and the open field test in adulthood. KYNA levels in the PFC of prenatally MAM-treated rats were also assessed. RESULTS: A significant cognitive impairment was observed in prenatally MAM-treated rats (p < 0.01), which was associated with enhanced PFC KYNA levels (p < 0.05). The peripubertal AM251, but not haloperidol, treatment ameliorated the cognitive deficit (p < 0.05), by normalizing the PFC KYNA content in MAM rats. CONCLUSIONS: The present findings suggest that the cognitive deficit observed in MAM rats may be related to enhanced PFC KYNA levels which could be, in turn, mediated by the activation of cannabinoid CB1 receptor. These results further support the modulation of brain KYNA levels as a potential therapeutic strategy to ameliorate the cognitive dysfunctions in schizophrenia.

• MeSH
• antipsychotika farmakologie   MeSH
• haloperidol farmakologie   MeSH
• kognitivní dysfunkce metabolismus   farmakoterapie   MeSH
• krysa rodu rattus MeSH
• kyselina kynurenová * metabolismus   MeSH
• methylazoxymethanolacetát * analogy a deriváty   MeSH
• modely nemocí na zvířatech MeSH
• piperidiny farmakologie   MeSH
• potkani Sprague-Dawley * MeSH
• prefrontální mozková kůra * metabolismus   účinky léků   MeSH
• pyrazoly farmakologie   MeSH
• receptor kanabinoidní CB1 metabolismus   MeSH
• schizofrenie * metabolismus   farmakoterapie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central nervous system and play an important role in the control of neural functions including neuronal activity, transmitter release and synaptic plasticity. Although the common subtypes of nAChRs are abundantly expressed throughout the brain, their expression in different brain regions and by individual neuronal types is not homogeneous or incidental. In recent years, several studies have emerged showing that particular subtypes of nAChRs are expressed by specific neuronal populations in which they have major influence on the activity of local circuits and behavior. It has been demonstrated that even nAChRs expressed by relatively rare neuronal types can induce significant changes in behavior and contribute to pathological processes. Depending on the identity and connectivity of the particular nAChRs-expressing neuronal populations, the activation of nAChRs can have distinct or even opposing effects on local neuronal signaling. In this review, we will summarize the available literature describing the expression of individual nicotinic subunits by different neuronal types in two crucial brain regions, the striatum and the prefrontal cortex. The review will also briefly discuss nicotinic expression in non-neuronal, glial cells, as they cannot be ignored as potential targets of nAChRs-modulating drugs. The final section will discuss options that could allow us to target nAChRs in a neuronal-type-specific manner, not only in the experimental field, but also eventually in clinical practice.

• MeSH
• corpus striatum metabolismus   MeSH
• lidé MeSH
• neurony * metabolismus   MeSH
• nikotinové receptory * metabolismus   MeSH
• prefrontální mozková kůra * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hypofunctioning of NMDA receptors, and the resulting shift in the balance between excitation and inhibition, is considered a key process in the pathophysiology of schizophrenia. One important manifestation of this phenomenon is changes in neural oscillations, those above 30 Hz (i.e., gamma-band oscillations), in particular. Although both preclinical and clinical studies observed increased gamma activity following acute administration of NMDA receptor antagonists, the relevance of this phenomenon has been recently questioned given the reduced gamma oscillations typically observed during sensory and cognitive tasks in schizophrenia. However, there is emerging, yet contradictory, evidence for increased spontaneous gamma-band activity (i.e., at rest or under baseline conditions). Here, we use the sub-chronic phencyclidine (PCP) rat model for schizophrenia, which has been argued to model the pathophysiology of schizophrenia more closely than acute NMDA antagonism, to investigate gamma oscillations (30-100 Hz) in the medial prefrontal cortex of anesthetized animals. While baseline gamma oscillations were not affected, oscillations induced by train stimulation of the posterior dorsal CA1 (pdCA1) field of the hippocampus were enhanced in PCP-treated animals (5 mg/kg, twice daily for 7 days, followed by a 7-day washout period). This effect was reversed by pharmacological enhancement of endocannabinoid levels via systemic administration of URB597 (0.3 mg/kg), an inhibitor of the catabolic enzyme of the endocannabinoid anandamide. Intriguingly, the pharmacological blockade of CB1 receptors by AM251 unmasked a reduced gamma oscillatory activity in PCP-treated animals. The findings are consistent with the observed effects of URB597 and AM251 on behavioral deficits reminiscent of the symptoms of schizophrenia and further validate the potential for cannabinoid-based drugs as a treatment for schizophrenia.

• MeSH
• amidohydrolasy * antagonisté a inhibitory   metabolismus   MeSH
• antagonisté excitačních aminokyselin farmakologie   aplikace a dávkování   MeSH
• benzamidy * farmakologie   MeSH
• endokanabinoidy metabolismus   MeSH
• fencyklidin * farmakologie   MeSH
• gama rytmus EEG fyziologie   účinky léků   MeSH
• karbamáty * farmakologie   MeSH
• krysa rodu rattus MeSH
• kyseliny arachidonové metabolismus   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• piperidiny * farmakologie   MeSH
• polynenasycené alkamidy metabolismus   farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• prefrontální mozková kůra účinky léků   metabolismus   patofyziologie   MeSH
• pyrazoly farmakologie   MeSH
• schizofrenie * patofyziologie   metabolismus   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The study aimed to assess the efficacy of transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric (NP) symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC), known as the long COVID. A double-blind, randomized, sham-controlled study compared the efficacy and safety of prefrontal cortex active tDCS to sham-tDCS in treating NP-PASC. Patients diagnosed with NP-PASC, with a Fatigue Impact Scale (FIS) score ≥ 40, were eligible for the study. Twenty tDCS sessions were administered within four weeks, with continuous, end-of-treatment, and follow-up measurements. The primary outcome was a change in the FIS at the end-of-treatment, analyzed in the intention-to-treat population. Data from 33 patients assigned to active (n = 16) or sham-tDCS (n = 17) were analyzed. After the treatment, a decrease in the FIS score was more pronounced in the sham than in the active group, yet the intergroup difference was insignificant (11.7 [95% CI -11.1 to 34.5], p = 0.6). Furthermore, no significant intergroup differences were observed regarding anxiety, depression, quality of life, and cognitive performance. The small cohort sample, differences in baseline FIS scores between groups (non-stratified randomization), or chosen stimulation parameters may have influenced our findings. However, it might also be possible that the expected mechanism of action of tDCS is insufficient to treat these conditions.

• MeSH
• COVID-19 * terapie   MeSH
• dvojitá slepá metoda MeSH
• kvalita života MeSH
• lidé MeSH
• postakutní syndrom COVID-19 MeSH
• prefrontální mozková kůra fyziologie   MeSH
• přímá transkraniální stimulace mozku * MeSH
• SARS-CoV-2 MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH