Cognitive flexibility

…but its precise contribution to higher cognitive functions and behavioral flexibility remains poorly understood. Here, we address this gap by focusing on synaptotagmin-7 (SYT7), a calcium sensor essential for facilitation---a form of STP in which high-frequency stimulation briefly enhances neurotransmitter release.

Humans and other animals must sometimes “think outside the box” to discover better strategies that solve old problems under novel conditions, but how the metaphorical “box” itself constrains learning is unknown. In operant tasks, the mechanisms behind learning are often framed just in terms of reinforcing success or punishing failure, and any predisposed strategies for guiding actions are ignored. In ethological behaviors though, animals often have instinctive predispositions in how they approach an evolutionarily adapted task but can also learn new ways to do better. Combining chemogenetics,

One of key hallmarks of cognitive flexibility is the capability of quickly performing neural computation to accommodate dynamic, context-switching environments and deal with task uncertainty [1-3]. Accumulating evidence from human and animal experiments have suggested that the mediodorsal (MD) thalamus and prefrontal cortex (PFC) are a pair of critical partners to achieve cognitive control. e found that such multiplicative thalamocortical gating enables a local Hebbian-weight amplification for prefrontal synaptic plasticity and is the key to facilitate a low-rank structure in prefrontal comput

The ability to learn and adapt to cognitive demands is vital for survival, and mice serve as valuable models in neuroscience for studying these processes. In this study, we introduce a novel maze framework to investigate learning and adaptability in mice, specifically focusing on humanized App knock-in models of Alzheimer's disease. The maze mimics decision-making scenarios, similar to when foraging, with an optimal reward path leading to a target with sucrose pellets. Decision nodes introduce off-reward routes to dead-ends or loops, creating a challenge requiring mice to balance exploration w

Cognitive flexibility is characterized by the ability to adapt behavior in response to changing environments. When the environment changes, previously appropriate behavior can lead to negative feedback. Surprising negative feedback – failure to receive a reward when strongly expected – may signal a change in the environment and the need to adjust action plans. Thus, processes that compute confidence and detect feedback at the timescale of individual decisions should interact with slower processes that infer environment changes. The neural mechanisms that underlie these hierarchical decisions r

…To test behavioral flexibility reversal learning paradigms are often used [1]. This flexible adaptation of entrained representations can be mediated by unlearning and forgetting [2]. One possible factor for passive forgetting could be the spontaneous remodeling of neuronal circuitry [3]. Acknowledging that previous studies have presented conflicting views on the effects of forgetting during reversal learning, we hypothesize two potential scenarios: Hypothesis I ('Reusing'): Reusing

Cognitive flexibility plays a key role in ensuring an individual's survival. The prefrontal cortex and striatum are both essential to cognitive flexibility but competing theories debate which structure among these two leads the role in detecting and representing new circumstances for a change, giving largely opposing predictions on neural activities in the prefrontal cortex and striatum during flexible behavior. We trained head-restrained mice to perform an action-outcome based dynamic foraging task and simultaneously recorded single-neuron activities in the medial prefrontal cortex (mPFC)

…Nonetheless, their role in regulating cognitive behavior remains to be clarified. Here, we demonstrated that RNF10-mediated synapse-to-nucleus signaling, linking activation of synaptic NMDARs to specific transcriptional programmes in the dorsal CA1, is necessary for cognitive flexibility. In vivo RNF10 downregulation, through gene deletion and silencing, induced, specifically in CA1, alterations of both long-term potentiation and dendritic spines’ structure. At behavioral level, RNF10 downregulation suppres

…social interaction, communication and cognitive flexibility. In the search of possible etiopathological mechanisms of ASDs, multiple studies linked aberrant mesolimbic reward pathway to dysfunction in sociability and restricted behaviors. However, the lateral habenula (LHb), representing the anti-reward center of the central nervous system, has been neglected so far. LHb activity encodes aversive responses and inhibits the physiological dynamics of ventral tegmental area (VTA), interfering w

Sensory discrimination tasks are valuable tools for investigating neuronal perception and learning mechanisms. While novel somatosensory discrimination tasks have been developed for electrophysiological or imaging studies in head-fixed mice, there remains a scarcity of tasks incorporating neurophysiological recordings within a more ecologically realistic setting involving freely moving animals. This study introduces a tactile discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, mice learn to discrimin

…neuronal plasticity, and aging-related cognitive alterations. Based on previous animal studies we hypothesized that neural ECM molecules like the proteoglycan brevican (BCAN) affect cognitive flexibility (CFL) also in humans. We addressed this hypothesis in young and older healthy human subjects by assessing flexibility performance and gray matter volumes (GMV) in dorsal anterior cingulate cortex (dACC), a key structure for cognitive control, together with serum concentrations of

…in visual processing, attention, and cognitive flexibility. Most of the studies have been using standard visual stimuli, but the advance of virtual reality (VR) tools is promising for better elucidating the dynamics of this neuromodulator in visually guided behaviors. The present study aims to explore the spatiotemporal activation of cortical cholinergic fibers during the presentation of a VR dynamic environment compared to standard visual stimuli using mesoscopic ACh imaging in awake mice.Choliner

Programmed cell death (PCD) is essential for regulating cell homeostasis in the developing brain. Cell populations that undergo massive PCD in the cortex include the first wave of oligodendrocyte precursor cells (firstOPCs) and most of GABAergic interneurons, which die postnatally within the same period. Furthermore, firstOPCs and most interneurons share common embryonic origins. Here we investigated how PCD of both firstOPCs and their lineage-related interneurons impact behavior and cortical networks. We used behavioral assays, patch-clamp recordings and immunostainings in two mouse models in

…the claustrum has been linked to cognitive control and, in particular, to cognitive flexibility in both animals and humans. Moreover, the claustrum has been reported to be involved in various aspects of sleep. In the present study, we explored resting-state functional connectivity of the claustrum in relation to both habitual sleep parameters and cognitive control performance in humans. Our aim was to explore the role

The prefrontal cortex is involved in cognitive flexibility. Independently of the task, individual and concerted neuronal activity is related to behaviour, task episodes, and prediction of future choices. However, not every choice arises from the same motivation. Choices can be spontaneous, based on information from previous experience, or querying for additional information. What are the neuronal dynamics governing these possibilities? We simultaneously record hundreds of individual neurons from the mouse prefrontal cortex using silicon probes. Head-fixed animals engage in a probabilistic 2-si

…structure, functional connectivity and cognitive function using a translational rhesus monkey model.Twenty seven female rhesus monkeys (13 dominant -DOM-, 14 subordinate -SUB-) received structural- and resting-state functional MRI scans to examine the volume of and functional connectivity (FC) between HIPPO and PFC subregions important for executive function, working memory and reward monitoring (dorsolateral PFC(dlPFC) -Area 46-; orbitofrontal cortex(OFC) -Area 13-; medial PFC(

…to help with various symptoms, cognitive deficits, particularly impaired executive functions, are often not addressed. In this study, we aim to investigate the effectiveness of HBK-15, a multimodal compound known for its rapid antidepressant-like effect, in reducing cognitive flexibility deficits in mice.We used male Balb/c mice. To assess the effect on cognitive flexibility, we used touchscreen-based two-choice pairw

Cognitive and social deficits are core to most psychiatric diseases. Dysfunctional connectivity in brain networks, including the prefrontal cortex (PFC) and its interacting subcortical structures, is supposed to elicit these deficits. Stress exposure and the ensuing release of glucocorticoid hormones is a common risk factor for psychiatric diseases and is known to modulate cognitive function partly through its binding to its receptor GR. The general aim of this work is to study the impact of stress exposure on PFC function and its extended brain networks. As expected, we show here that repeate

…risk of depression, anxiety, and cognitive impairment, exacerbating the global health issue of age-related cognitive decline. Research on the effects of SI in older animals is limited. However, in humans, the negative effects of SI become more pronounced with age, with a particularly strong effect on males. Our study examines the impact of SI on cogn

The ability to predict the consequences of behavior and the flexibility to modify behavior based on outcome and changes in reward contingency is critical for not only survival but also for maximizing reward. Acquisition and consolidation of social reward contingencies is essential for both prediction and flexibility. During the presentation of emotionally charged stimuli, the amygdala encodes the salience of social stimuli as ensembles of neurons with individual stimuli preferences. Correct evaluation of prediction errors, defined as the difference between expectation and result, is critical f

Cognitive flexibility is critical for enabling humans and animals to maintain and maximize rewarding outcomes in a changing environment, and often compromised in various psychiatric conditions including Schizophrenia (Lotus Thai, et al, 2019; Zhu, Ho-wai So, et al, 2021). Prefrontal cortex (PFC) and basal ganglia (BG) are both important brain systems in establishing and switching between flexible goal-directed strategies, and repetitive behaviours (Merre, et al, 2018; Hart, Balleine et al, 2014). The direct anatomical connection between PFC and striatum (STR; the input nucleus of BG) is consid

Cannabis consumption, particularly among adolescents, has surged over the last decades. Adolescence is a critical period for brain development during which the prefrontal cortex (PFC) completes its maturation. There is strong evidence that the endocannabinoid system is a key regulator of brain development and of maturation of the PFC during adolescence. However, whether chronic cannabinoid receptor activation during this stage of development has long-term consequences for PFC function and associated behaviors remains unexplored. Here we show that repeated injection of cannabinoid receptor agon

Cognitive flexibility is a function of the prefrontal cortex (PFC) that allows shifting strategies to adjust performance in changing environments. The dorsal raphe nucleus (DRN) provides most of the serotonergic inputs to the PFC. Clinical and pharmacological evidence suggests that prefrontal impairments or serotonergic alterations affect cognitive flexibility. However, the neuronal correlates of cognitive flexibility are largely unknown, and whether modulation of the neuronal activity in the DRN affects flexible behaviors remains unclear. We investigated how projections from the DRN modulate

Depression is a serious mental illness that includes both behavioral symptoms and cognitive dysfunction. With the growing problem of ineffective treatment, there is a constant need for compounds with rapid antidepressant and procognitive effects. A compound that has shown antidepressant-like activity after single administration in animal models is NLX-101. NLX-101 preferentially activates postsynaptic 5-HT1A heteroreceptors in the prefrontal cortex, stimulating extracellular signal-regulated kinase (ERK1/2) phosphorylation. Thus, this study aimed to evaluate the potential ability of NLX-101 to