The hippocampus (HPC) is essential for navigation and memory, tracking environmental continuity and change, including navigation relative to moving targets. CA1 ensembles expressing immediate-early gene (IEG) Arc and Homer1a RNA are contextually specific. While IEG expression correlates with HPC-dependent task demands, the effects of behavioral demands on IEG-expressing ensembles remain unclear.
View Article and Find Full Text PDFEffort-based decision-making is particularly relevant to psychiatric conditions where motivation deficits are prominent features. Despite its clinical significance, the neurochemical mechanisms of this cognitive process remain unclarified. This study explores the impact of serotonin synthesis inhibition (PCPA) and modulation of serotonin release and 5-HT1A receptor agonism (8-OH-DPAT) on effort-based decision-making in rats.
View Article and Find Full Text PDFEpisodic memory, the ability to recall specific events and experiences, is a cornerstone of human cognition with profound clinical implications. While animal studies have provided valuable insights into the neuronal underpinnings of episodic memory, research has largely relied on a limited subset of tasks that model only some aspects of episodic memory. In this narrative review, we provide an overview of rodent episodic-like memory tasks that expand the methodological repertoire and diversify the approaches used in episodic-like memory research.
View Article and Find Full Text PDFChemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibiting or excitating neuronal subpopulations were designed in the past few decades.
View Article and Find Full Text PDFFinding a cure for Alzheimer's disease (AD) has been notoriously challenging for many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing the progression in the earliest stages. A better understanding of underlying mechanisms at the beginning of the disease could aid in early diagnosis and intervention, including alleviating symptoms or slowing down the disease progression.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
December 2023
Dopamine type 2 receptors (DRs) constitute the main molecular target in the pharmacotherapy of schizophrenia. However, the second and third generation of antipsychotics comprises multi-target ligands, also binding serotonin type 3 receptors (5-HTRs) and other receptor classes as well. Here, we examined two experimental compounds (marked compound K1697 and K1700) from the group of 1,4-di-substituted aromatic piperazines, previously described in the study of Juza et al.
View Article and Find Full Text PDFWe designed a behavioral task called One-Trial Trace Escape Reaction (OTTER), in which rats incidentally associate two temporally discontinuous stimuli: a neutral acoustic cue (CS) with an aversive stimulus (US) which occurs two seconds later (CS-2s-US sequence). Rats are first habituated to two similar environmental contexts (A and B), each consisting of an interconnected dark and light chamber. Next, rats experience the CS-2s-US sequence in the dark chamber of one of the contexts (either A or B); the US is terminated immediately after a rat escapes into the light chamber.
View Article and Find Full Text PDFSchizophrenia research has increased in recent decades and focused more on its neural basis. Decision-making and cognitive flexibility are the main cognitive functions that are impaired and considered schizophrenia endophenotypes. Cognitive impairment was recently connected with altered functions of N-methyl-d-aspartate (NMDAR) glutamatergic receptors, which increased cortical activity.
View Article and Find Full Text PDFThe amyloid cascade hypothesis, focusing on pathological proteins aggregation, has so far failed to uncover the root cause of Alzheimer's disease (AD), or to provide an effective therapy. This traditional paradigm essentially explains a mechanism involved in the development of sporadic AD rather than its cause. The failure of an overwhelming majority of clinical studies (99.
View Article and Find Full Text PDFMaternal immune activation has been identified as a significant risk factor for schizophrenia. Using rodent models, past work has demonstrated various behavioral and brain impairments in offspring after immune-activating events. We applied 5 mg/kg of poly(I:C) on gestation day 9 to pregnant mouse dams, whose offspring were then stressed during puberty.
View Article and Find Full Text PDFSchizophrenia is severe neuropsychiatric disease, which is commonly accompanied not only by positive or negative symptoms, but also by cognitive impairment. To study neuronal mechanisms underlying cognitive distortions and mechanisms underlying schizophrenia, animal pharmacological models of cognitive symptoms are commonly used. Between various cognitive impairments in schizophrenia patients, disturbed time perception has often been reported.
View Article and Find Full Text PDFChronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole-glutamate-modulating agents that have been shown to be effective in several clinical trials.
View Article and Find Full Text PDFSchizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood.
View Article and Find Full Text PDFNeural components enabling flexible cognition and behavior are well-established, and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. However, dense projections from the ventral hippocampus (vHPC) alter the functioning of the medial PFC (mPFC). Dysfunctional hippocampo-prefrontal connectivity negatively affects the integrity of flexible cognition, especially in patients with schizophrenia.
View Article and Find Full Text PDFIt is well known that communication between the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC) is critical for various cognitive and behavioral functions. However, the exact role of these structures in spatial coordination remains to be clarified. Here we sought to determine the involvement of the mPFC and the vHPC in the spatial retrieval of a previously learned active place avoidance task in adult male Long-Evans rats, using a combination of unilateral and bilateral local muscimol inactivations.
View Article and Find Full Text PDFMaternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery.
View Article and Find Full Text PDFQuinpirole (QNP) sensitization is a well-established model of stereotypical checking relevant to obsessive-compulsive disorder. Previously, we found that QNP-treated rats display deficits in hippocampus-dependent tasks. The present study explores the expression of immediate early genes (IEG) during QNP-induced stereotypical checking in the hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFAnimals can organize their behavior with respect to other moving animals or objects; when hunting or escaping a predator, when migrating in groups or during various social interactions. In rats, we aimed to characterize spatial behaviors relative to moving objects and to explore the cognitive mechanisms controlling these behaviors. Three groups of animals were trained to avoid a mild foot-shock delivered in one of three positions: either in front, on the left side, or on the right side of a moving robot.
View Article and Find Full Text PDFThe nucleus-encoded 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) regulates cyclophilin D (cypD) in the mitochondrial matrix. CypD regulates opening of mitochondrial permeability transition pores. Both mechanisms may be affected by amyloid β peptides accumulated in mitochondria in Alzheimer's disease (AD).
View Article and Find Full Text PDFRegulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2 mice we demonstrate that CRMP2 has a moderate effect on Sema3A-dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum.
View Article and Find Full Text PDFEpilepsy, the most common neurologic disorder in childhood, is associated with a subset of psychiatric dysfunctions, including cognitive deficits, and alterations in emotionality (e.g., anxiety and depression) and social functioning.
View Article and Find Full Text PDFMemory is related to the function of N-methyl-D-aspartate (NMDA) receptors. Depending on the dose, NMDA receptor antagonists (such as memantine or MK-801) can impair memory and/or cognitive as well as procedural functions, while they also can prevent the long-term toxic effects of over-excitation of these receptors in pathophysiological processes. There is an unresolved question of whether memantine at low doses could exert an acute pro-cognitive activity.
View Article and Find Full Text PDFDespite the substantial knowledge accumulated by past research, the exact mechanisms of the pathogenesis of schizophrenia and causal treatments still remain unclear. Deficits of cognition and information processing in schizophrenia are today often viewed as the primary and core symptoms of this devastating disorder. These deficits likely result from disruptions in the coordination of neuronal and neural activity.
View Article and Find Full Text PDFRationale: Chronic quinpirole (QNP) sensitization is an established animal model relevant to obsessive-compulsive disorder (OCD) that has been previously shown to induce several OCD-like behavioral patterns, such as compulsive-like checking and increased locomotion.
Objectives: In current study we explored the effect of antiglutamatergic drugs, memantine and riluzole, on cognitive and behavioral performance of QNP sensitized rats.
Methods: During habituation phase, the rats (N = 56) were injected with QNP (0.