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GO/noGO tasks enable assessing decision-making processes and the ability to suppress a specific action according to the context. Here, rats had to discriminate between 2 visual stimuli (GO or noGO) shown on an iPad screen. The execution (for GO) or nonexecution (for noGO) of the selected action (to touch or not the visual display) were reinforced with food. The main goal was to record and to analyze local field potentials collected from cortical and subcortical structures when the visual stimuli were shown on the touch screen and during the subsequent activities. Rats were implanted with recording electrodes in the prelimbic cortex, primary motor cortex, nucleus accumbens septi, basolateral amygdala, dorsolateral and dorsomedial striatum, hippocampal CA1, and mediodorsal thalamic nucleus. Spectral analyses of the collected data demonstrate that the prelimbic cortex was selectively involved in the cognitive and motivational processing of the learning task but not in the execution of reward-directed behaviors. In addition, the other recorded structures presented specific tendencies to be involved in these 2 types of brain activity in response to the presentation of GO or noGO stimuli. Spectral analyses, spectrograms, and coherence between the recorded brain areas indicate their specific involvement in GO vs. noGO tasks.

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This work aimed to synthesize and characterize a biocompatible hydrogel of alginate and chitosan enriched with iron sulfide nanocrystals. Three concentrations of iron sulfide nanocrystals (FeS2NCs) 0.03905, 0.0781, and 0.2343 mg/ml were used. Gel swelling was determined using phosphate-buffered saline solution at 1, 2, 4, 6, 24, 48, and 72 h. The microstructure, the morphology, and the elastic strength were determined by optical microscopy, scanning electron microscopy, and rheological studies, respectively. The functional groups were identified through Fourier Transform Infrared spectroscopy. Biocompatibility was determined in a murine model; after seven days of subdermal inoculation, histological sections stained with H&E were analyzed, and then histopathological features were evaluated. All the compounds obtained showed a loss modulus lower than the storage modulus. The 0.2343 mg/ml FeS2NCs hydrogel showed higher swelling than the control. In the in vivo evaluation, no adverse effects were found. The presence of FeS2NCs was well tolerated in the subcutaneous tissue of mice, according to histopathological analysis. The hydrogels synthesized with added FeS2NCs demonstrate a swelling ratio of 150 %, rheologically exhibiting gel-like behavior rather than viscous liquids. Furthermore, they did not present any adverse effects on the subcutaneous tissue.

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The hippocampus is crucial for acquiring and retrieving episodic and contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- and optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced hyperpolarization and reported that the previously formed memory was erased, thus concluding that denate gyrus is needed for memory maintenance. The other study used optogenetic with halorhodopsin induced hyperpolarization and reported and dentate gyrus is needed for memory retrieval. We hypothesized that this apparent discrepancy could be due to the length of hyperpolarization in previous studies; minutes by optogenetics and several hours by DREADD/CNO. Since hyperpolarization interferes with anterograde and retrograde neuronal signaling, it is possible that the memory engram in the dentate gyrus and the entorhinal to hippocampus trisynaptic circuit was erased by long-term, but not with short-term hyperpolarization. We developed and applied an advanced chemogenetic technology to selectively silence synaptic output by blocking neurotransmitter release without hyperpolarizing DG neurons to explore this apparent discrepancy. We performed in vivo electrophysiology during trace eyeblink in a rabbit model of associative learning. Our work shows that the DG output is required for memory retrieval. Based on previous and recent findings, we propose that the actively functional anterograde and retrograde neuronal signaling is necessary to preserve synaptic memory engrams along the entorhinal cortex to the hippocampal trisynaptic circuit.

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Learning is a functional state of the brain that should be understood as a continuous process, rather than being restricted to the very moment of its acquisition, storage, or retrieval. The cerebellum operates by comparing predicted states with actual states, learning from errors, and updating its internal representation to minimize errors. In this regard, we studied cerebellar interpositus nucleus (IPn) functional capabilities by recording its unitary activity in behaving rabbits during an associative learning task: the classical conditioning of eyelid responses. We recorded IPn neurons in rabbits during classical eyeblink conditioning using a delay paradigm. We found that IPn neurons reduce error signals across conditioning sessions, simultaneously increasing and transmitting spikes before the onset of the unconditioned stimulus. Thus, IPn neurons generate predictions that optimize in time and shape the conditioned eyeblink response. Our results are consistent with the idea that the cerebellum works under Bayesian rules updating the weights using the previous history.

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BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease characterized by motor deficits and cognitive decline. Many immune aspects of the disease are understood through studies in the experimental autoimmune encephalomyelitis (EAE) model, including the contribution of the NF-κB transcription factor to neuroinflammation. However, the cell-specific roles of NF-κB to EAE and its cognitive comorbidities still needs further investigation. We have previously shown that the myeloid cell NF-κB plays a role in the healthy brain by exerting homeostatic regulation of neuronal excitability and synaptic plasticity and here we investigated its role in EAE. METHODS: We used constitutive MφIKKßΚΟ mice, in which depletion of IKKß, the main activating kinase of NF-κB, was global to CNS and peripheral macrophages, and ΜgΙΚΚßKO mice, in which depletion was inducible and specific to CNS macrophages by 28 days after tamoxifen administration. We subjected these mice to MOG35-55 induced EAE and cuprizone-induced demyelination. We measured pathology by immunohistochemistry, investigated molecular mechanisms by RNA sequencing analysis and studied neuronal functions by in vivo electrophysiology in awake animals. RESULTS: Global depletion of IKKß from myeloid cells in MφIKKßΚΟ mice accelerated the onset and significantly supressed chronic EAE. Knocking out IKKß only from CNS resident macrophages accelerated the onset and exacerbated chronic EAE, accompanied by earlier demyelination and immune cell infiltration but had no effect in cuprizone-induced demyelination. Peripheral T cell effector functions were not affected by myeloid cell deletion of IKKß, but CNS resident mechanisms, such as microglial activation and neuronal hyperexcitability were altered from early in EAE. Lastly, depletion of myeloid cell IKKß resulted in enhanced late long-term potentiation in EAE. CONCLUSIONS: IKKß-mediated activation of NF-κΒ in myeloid cells has opposing roles in EAE depending on the cell type and the disease stage. In CNS macrophages it is protective while in peripheral macrophages it is disease-promoting and acts mainly during chronic disease. Although clinically protective, CNS myeloid cell IKKß deletion dysregulates neuronal excitability and synaptic plasticity in EAE. These effects of IKKß on brain cognitive abilities deserve special consideration when therapeutic interventions that inhibit NF-κB are used in MS.

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BACKGROUND: Some research suggests that post-stroke aphasia can recover "on its own", however, there is evidence of a common neural substrate for motor and language systems. We hypothesize, that motor neurorehabilitation of hemiparesis could be related to simultaneous improvement in aphasia. OBJECTIVE: To measure changes in post-stroke aphasia and its relation with hemiparesis treated with different therapies. METHODS: Database information (n = 32) on post-stroke hemiparesis (Fugl-Meyer Scale evaluated) managed with virtual reality (VR) versus modified constraint-induced movement therapy (mCIMT) or regular therapy (rPT/OT) was analyzed. None received logotherapy (LT) by appointment at four months. INCLUSION CRITERIA: < 3 months after the stroke, aphasia severe (Boston Aphasia Intensity Scale), and all three evaluations. RESULTS: Twenty-one patient records met inclusion criteria (71,4% women and mean age 66,67±3,13 years) who received VR, mCIMT, or rPT/OT (n = 6, 8, and 7, respectively). There was continuous intra-groups improvement in aphasia (p < 0.05), but inter-groups the greater aphasia recovery (p = 0.05) and hemiparesis (p = 0.02) were in VR, with a high correlation in evolution between them (r = 0.73; p = 0.047). CONCLUSION: High clinical correlation between aphasia, without LT, and hemiparesis evolution during motor neurorehabilitation would support common neural connections stimulation. We will conduct a clinical trial, with a larger sample size to contrast our hypothesis.

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The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for "printing" memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval.

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During embryonic development, heterozygous mutant kreisler mice undergo ectopic expression of the Hoxa3 gene in the rostral hindbrain, affecting the opioid and noradrenergic systems. In this model, we have investigated behavioral and cognitive processes in their adulthood. We confirmed that pontine and locus coeruleus neuronal projections are impaired, by using startle and pain tests and by analyzing immunohistochemical localization of tyrosine hydroxylase. Our results showed that, even if kreisler mice are able to generate eyelid reflex responses, there are differences with wild-types in the first component of the response (R1), modulated by the noradrenergic system. The acquisition of conditioned motor responses is impaired in kreisler mice when using the trace but not the delay paradigm, suggesting a functional impairment in the hippocampus, subsequently confirmed by reduced quantification of alpha2a receptor mRNA expression in this area but not in the cerebellum. Moreover, we demonstrate the involvement of adrenergic projection in eyelid classical conditioning, as clonidine prevents the appearance of eyelid conditioned responses in wild-type mice. In addition, hippocampal motor learning ability was restored in kreisler mice by administration of adrenergic antagonist drugs, and a synergistic effect was observed following simultaneous administration of idazoxan and naloxone.

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Learning and memory occurrence requires of hippocampal long-term synaptic plasticity and precise neural activity orchestrated by brain network oscillations, both processes reciprocally influencing each other. As G-protein-gated inwardly rectifying potassium (GIRK) channels rule synaptic plasticity that supports hippocampal-dependent memory, here we assessed their unknown role in hippocampal oscillatory activity in relation to synaptic plasticity induction. In alert male mice, pharmacological GIRK modulation did not alter neural oscillations before long-term potentiation (LTP) induction. However, after an LTP generating protocol, both gain- and loss-of basal GIRK activity transformed LTP into long-term depression, but only specific suppression of constitutive GIRK activity caused a disruption of network synchronization (δ, α, γ bands), even leading to long-lasting ripples and fast ripples pathological oscillations. Together, our data showed that constitutive GIRK activity plays a key role in the tuning mechanism of hippocampal oscillatory activity during long-term synaptic plasticity processes that underlies hippocampal-dependent cognitive functions.

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To watch a person doing an activity has an impact on the viewer. In fact, the film industry hinges on viewers looking at characters doing all sorts of narrative activities. From previous works, we know that media and non-media professionals perceive differently audiovisuals with cuts. Media professionals present a lower eye-blink rate, a lower activity in frontal and central cortical areas, and a more organized functional brain connectivity when watching audiovisual cuts. Here, we aimed to determine how audiovisuals with no formal interruptions such as cuts were perceived by media and non-media professionals. Moreover, we wondered how motor actions of characters in films would have an impact on the brain activities of the two groups of observers. We presented a narrative with 24 motor actions in a one-shot movie in wide shot with no cuts to 40 participants. We recorded the electroencephalographic (EEG) activity of the participants and analyzed it for the periods corresponding to the 24 motor actions (24 actions × 40 participants = 960 potential trials). In accordance with collected results, we observed differences in the EEG activity of the left primary motor cortex. A spectral analysis of recorded EEG traces indicated the presence of significant differences in the beta band between the two groups after the onset of the motor activities, while no such differences were found in the alpha band. We concluded that media expertise is related with the beta band identified in the EEG activity of the left primary motor cortex and the observation of motor actions in videos.

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N-methyl-D-aspartate (NMDA) receptor hypofunctionality is a well-studied hypothesis for schizophrenia pathophysiology, and daily dosing of the NMDA receptor co-agonist, D-serine, in clinical trials has shown positive effects in patients. Therefore, inhibition of D-amino acid oxidase (DAAO) has the potential to be a new therapeutic approach for the treatment of schizophrenia. TAK-831 (luvadaxistat), a novel, highly potent inhibitor of DAAO, significantly increases D-serine levels in the rodent brain, plasma, and cerebrospinal fluid. This study shows luvadaxistat to be efficacious in animal tests of cognition and in a translational animal model for cognitive impairment in schizophrenia. This is demonstrated when luvadaxistat is dosed alone and in conjunction with a typical antipsychotic. When dosed chronically, there is a suggestion of change in synaptic plasticity as seen by a leftward shift in the maximum efficacious dose in several studies. This is suggestive of enhanced activation of NMDA receptors in the brain and confirmed by modulation of long-term potentiation after chronic dosing. DAAO is highly expressed in the cerebellum, an area of increasing interest for schizophrenia, and luvadaxistat was shown to be efficacious in a cerebellar-dependent associative learning task. While luvadaxistat ameliorated the deficit seen in sociability in two different negative symptom tests of social interaction, it failed to show an effect in endpoints of negative symptoms in clinical trials. These results suggest that luvadaxistat potentially could be used to improve cognitive impairment in patients with schizophrenia, which is not well addressed with current antipsychotic medications.

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This review presents a broad perspective of the Neuroscience of our days with special attention to how the brain generates our behaviors, emotions, and mental states. It describes in detail how unconscious and conscious processing of sensorimotor and mental information takes place in our brains. Likewise, classic and recent experiments illustrating the neuroscientific foundations regarding the behavioral and cognitive abilities of animals and, in particular, of human beings are described. Special attention is applied to the description of the different neural regulatory systems dealing with behavioral, cognitive, and emotional functions. Finally, the brain process for decision-making, and its relationship with individual free will and responsibility, are also described.

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BACKGROUND: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. METHODS: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. RESULTS: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by ß adrenergic receptors. A reduction in extracellular Ca2+ concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, ß adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. LIMITATIONS: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. CONCLUSIONS: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS.

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The analysis of the topography of brain neuromodulation following transcranial alternating current (AC) stimulation is relevant for defining strategies directed to specific nuclei stimulation in patients. Among the different procedures of AC stimulation, temporal interference (tTIS) is a novel method for non-invasive neuromodulation of specific deep brain targets. However, little information is currently available about its tissue effects and its activation topography in in vivo animal models. After a single session (30 min, 0.12 mA) of transcranial alternate current (2,000 Hz; ES/AC group) or tTIS (2,000/2,010 Hz; Es/tTIS group) stimulation, rat brains were explored by whole-brain mapping analysis of c-Fos immunostained serial sections. For this analysis, we used two mapping methods, namely density-to-color processed channels (independent component analysis (ICA) and graphical representation (MATLAB) of morphometrical and densitometrical values obtained by density threshold segmentation. In addition, to assess tissue effects, alternate serial sections were stained for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and Nissl. AC stimulation induced a mild superficial increase in c-Fos immunoreactivity. However, tTIS stimulation globally decreased the number of c-Fos-positive neurons and increased blood brain barrier cell immunoreactivity. tTIS also had a stronger effect around the electrode placement area and preserved neuronal activation better in restricted areas of the deep brain (directional stimulation). The enhanced activation of intramural blood vessels' cells and perivascular astrocytes suggests that low-frequency interference (10 Hz) may also have a trophic effect.

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Objetivo: explorar el concepto de <<etnias>>, en un grupo de estudiantes de Odontología de una universidad privada. Métodos: Se realizó un estudio cualitativo con 11 estudiantes entre 18 y 21 años en una Facultad de Odontología de una Universidad de Bogotá, en el curso de Socio Humanística I. Se efectuó una entrevista semiestructurada a cada estudiante; se obtuvo el consentimiento informado, el estudio fue clasificado como sin riesgo. Se aplicó en una sesión una entrevista semiestructurada, organizada en forma de historia donde el estudiante se involucra al leer el relato y contestar los interrogantes a medida que transcurría la lectura, lo que sirvió como base para el análisis de contenido. Resultados: Se determinaron tres categorías a saber: concepto de etnia, grupos étnicos en Colombia y enfoque diferencial étnico en salud, encontrándose que la etnia para los estudiantes es el reconocimiento de multietnicidad y pluriculturalidad del país, acompañado de diversidad. Conclusión: Con relación al concepto de etnia, se resalta que para algunos de los encuestados hay una confusión con representar los grupos étnicos como: madres cabeza de hogar, desplazados y población LGBTI. Los estudiantes respondieron "Raizales, negritudes, indígenas, Rom, desplazados, adultez, vejez, niñez, LGTBI." Que, aunque tienen relación con el enfoque diferencial, no corresponden al interrogante planteado en la historia.

Objective: to explore the concept of ethnicity in a group of odontology students of a private university. Methods: A qualitative study was carried out with 11 students between 18 and 21 years of age in an odontology faculty of a university in Bogota, in the course of socio-humanistic I. A semi-structured interview was conducted with each student, aninformed consent was obtained, and the study was classified as risk-free. A semi-structured interview was applied in one session, organized in the form of a story where the student was involved by reading the story and answering the questions as the reading progressed, which served as a basis for the content analysis. Results: Three categories were determined: concept of ethnicity, ethnic groups in Colombia and ethnic differential approach in health, finding that ethnicity for students is the recognition of multiethnicity and multiculturalism of the country, accompanied by diversity. Conclusion: In relation to the concept of ethnicity, a highlight is that for some of the participants there is confusion with representing ethnic groups such as: single mothers, displaced people and LGBTI population. The students answered "Raizal, black people, indigenous people, Rom, displaced, adults, elders, children, LGTBI". Although they are related to the differential approach, they do not correspond to the question raised in the story.

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For almost a century the classical conditioning of nictitating membrane/eyelid responses has been used as an excellent and feasible experimental model to study how the brain organizes the acquisition, storage, and retrieval of new motor abilities in alert behaving mammals, including humans. Lesional, pharmacological, and electrophysiological approaches, and more recently, genetically manipulated animals have shown the involvement of numerous brain areas in this apparently simple example of associative learning. In this regard, the cerebellum (both cortex and nuclei) has received particular attention as a putative site for the acquisition and storage of eyelid conditioned responses, a proposal not fully accepted by all researchers. Indeed, the acquisition of this type of learning implies the activation of many neural processes dealing with the sensorimotor integration and the kinematics of the acquired ability, as well as with the attentional and cognitive aspects also involved in this process. Here, we address specifically the functional roles of three brain structures (red nucleus, cerebellar interpositus nucleus, and motor cortex) mainly involved in the acquisition and performance of eyelid conditioned responses and three other brain structures (hippocampus, medial prefrontal cortex, and claustrum) related to non-motor aspects of the acquisition process. The main conclusion is that the acquisition of this motor ability results from the contribution of many cortical and subcortical brain structures each one involved in specific (motor and cognitive) aspects of the learning process.

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Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3-CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABAA-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3-CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.

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ß-hydroxy ß-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.

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