Impact of Sleep Deprivation on the Brain's Inflammatory Response Triggered by Lipopolysaccharide and Its Consequences on Spatial Learning and Memory and Long-Term Potentiation in Male Rats.

INTRODUCTION: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions. METHODS: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1ß (IL-1ß) levels were significantly higher in the LPS1+SD group than in the Saline group. CONCLUSION: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Morphine exposure modulates dimensional bias and set formation in anthropoids.

Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant 'switch cost'. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.

Error modulates categorization of subsecond durations in multitasking contexts.

Monitoring errors consumes limited cognitive resources and can disrupt subsequent task performance in multitasking scenarios. However, there is a dearth of empirical evidence concerning this interference with prospective estimation of time. In this study, we sought to investigate this issue through a serial multitasking experiment, employing a temporal bisection task as the primary task. We introduced two task contexts by implementing two different concurrent tasks. In one context, participants were tasked with discriminating the size difference between two visual items, while in the other context, they were required to judge the temporal order of similar visual items. The primary task remained the same for the entire experiment. Psychophysical metrics, including subjective bias (determined by the bisection point) and temporal sensitivity (measured by the Weber ratio), in addition to reaction time, remained unaltered in the primary task regardless of the perceptual context exerted by the concurrent tasks. However, commission of error in the concurrent tasks (i.e., non-specific errors) led to a right-ward shift in the bisection point, indicating underestimation of time after errors. Applying a drift-diffusion framework for temporal decision making, we observed alterations in the starting point and drift rate parameters, supporting the error-induced underestimation of time. The error-induced effects were all diminished with increasing a delay between the primary and concurrent task, indicating an adaptive response to errors at a trial level. Furthermore, the error-induced shift in the bisection point was diminished in the second half of the experiment, probably because of a decline in error significance and subsequent monitoring response. These findings indicate that non-specific errors impact the prospective estimation of time in multitasking scenarios, yet their effects can be alleviated through both local and global reallocation of cognitive resources from error processing to time processing.

The Effects of Chronic Marijuana Administration on 6-OHDA-Induced Learning & Memory Impairment and Hippocampal Dopamine and Cannabinoid Receptors Interaction in Male Rats.

There are general inhibitory effects of exo-cannabinoids on dopamine-mediated behaviors. Many studies suggested the interaction between cannabinoid receptors and dopamine receptors in the brain that affect cognition behaviors. In this paper, we investigate the effects of marijuana on 6-OHDA-induced cognitive impairments and the expression of dopamine and cannabinoid receptors in the hippocampus of male rats. 42 rats were divided into six groups. 6-hydroxy dopamine (6-OHDA) was administrated into the substantia nigra. Marijuana (60 mg/kg; i.p.) was administered 28 days, one week after the 6-OHDA injection. Morris water maze (MWM) and novel object recognition tests were performed. The hippocampal expression levels of cannabinoid receptors and D1 and D2 dopamine receptors evaluate by real-time PCR. The results showed marijuana improved the spatial learning and memory disorders caused by 6-OHDA in the MVM task and novel object recognition test. Additionally, the level of both D1 and D2 mRNA was decreased in 6-OHDA-treated animals and marijuana consumption only increased the hippocampal level of D1 mRNA. Moreover, the level of hippocampal CB1 mRNA in 6-OHDA- treated rats was higher than in control rats. However, the hippocampal level of CB2 mRNA was decreased in 6-OHDA- treated rats. Marijuana consumption caused a significant decrease in CB1 mRNA level and an increase in CB2 mRNA level in 6-OHDA + marijuana group. Therefore, marijuana may be helpful for learning & memory disorders, D1, and D2 dopamine receptors, and cannabinoid receptor alteration in patients with Parkinson's disease.

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist.

Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48-50 (PND 48-50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48-50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups.

L-carnitine attenuates acoustic startle reflex dysfunction in adult male rats exposed to mancozeb.

The fungicide mancozeb increases oxygen-free radicals in the central nervous system. As an antioxidant, L-carnitine protects DNA and cell membranes from damage caused by oxygen-free radicals. The present study investigated how L-carnitine affected the acoustic startle response (ASR) in rats exposed to mancozeb. In this experimental study, male Wistar rats were gavaged orally with mancozeb (500, 1000, and 2000 mg/kg), L-carnitine (100, 200, and 400 mg/kg), or L-carnitine (200 mg/kg) + mancozeb (500 mg/kg) three times in 1 week. In the sham group, saline (0.9%, 10 mL/kg) was gavaged at a volume equivalent to that of the drugs. The control group did not receive any treatment. The results showed that locomotor activity and the percentage of prepulse inhibition in the mancozeb groups decreased compared to the sham group while these parameters increased in the L-carnitine group (200 mg/kg) compared to sham rats. In conclusion, mancozeb may increase the risk factor for cognitive diseases such as schizophrenia in people exposed to it while pretreatment with L-carnitine can attenuate the toxic effect.

Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model.

Cerebellar ataxia is a neurodegenerative disorder leading to severe motor incoordination. Recently, it has been suggested that cannabinoids play a role in modulating ataxic symptoms. To understand the possible therapeutic effect of cannabinoids for the management of cerebellar ataxia, we used cannabinoid agonist/antagonists to target the cannabinoid type 1 receptor (CB1R) in the 3 acetyl pyridine (3AP) rat model of ataxia. The role of the CB1R was examined using three different doses of the CB1R agonist, WIN-55,212-2 (WIN; 0.1, 0.5, 1 mg/kg) administrated 30 min prior to 3AP (55 mg/kg, i.p.) which leads to motor impairment through destruction of the inferior olive. In some groups, the CB1R antagonist AM251 (1 mg/kg) was given in combination with WIN. Locomotor activity and motor coordination were impaired by 3AP, and the application of WIN did not ameliorate this effect. However, the abnormal gait, rearing and grooming caused by 3AP were prevented by co-administration of AM251 with WIN. While the addition of the CB1R antagonist improved some ataxic symptoms, there was no effect of AM251 on balance or locomotor activity when co-administrated with WIN. Behavioral testing indicated that not only did WIN fail to exert any protective effect on ataxic symptoms; it exacerbated ataxic symptoms, suggesting that CB1R agonists may not be the ideal therapeutic drug in this disorder. When taken together, the findings from the present study indicate that cannabinoid modulation of ataxia symptoms may not act solely through CB1Rs and other cannabinoid receptors should be considered in future studies.

The cannabinoid antagonist, AM251 attenuates ataxia related deficiencies in a cerebellar ataxic model.

Aim: Disruption in cerebellar inputs, as well as dysfunction of Purkinje cells (PCs), causes a change in the timing of electrical signaling in the cerebellum resulting in disorders such as cerebellar ataxia. Although much clinical and molecular genetics research has been conducted to understand this disorder, there is no specific treatment for cerebellar ataxia. As cannabinoid type 1 receptors (CB1Rs) are highly expressed in the cerebellum and have been suggested as a therapeutic strategy, we determined whether AM251, a cannabinoid receptor antagonist, was neuroprotective of PCs in a rat cerebellar ataxic model.Materials and methods: To this end, we conducted behavioral and histological tests in the 3-acetylpyridine (3AP) rat cerebellar ataxia model, to explore whether AM251 was protective against induction of ataxia and cell death.Results: Rats with chemical degeneration of the inferior olive induced by 3AP (55 mg/kg, i.p.) clearly showed cerebellar ataxic symptoms. The locomotor activity and motor coordination of the ataxic animals were clearly disrupted compared to the control group. Further, histological analysis showed cell death and PCs degenerated with loss of cell membrane integrity associated with 3AP. Pre-treatment by AM251 improved the locomotor activity of the ataxic animals, and AM251 almost prevented PCs neuronal degeneration.Conclusion: Our data which show protection of cerebellar PCs and motor improvement in the ataxic rat model by treatment with AM251 suggests that targeting cannabinoid receptors should be considered for therapeutic intervention in cerebellar ataxia. HIGHLIGHTS:AM251 was protective against induction of ataxia and cell death.CBR antagonist typically ameliorated 3AP induced Ataxia.AM251 affected explorative and gait disturbances induced by 3AP.CBR antagonist improved impairments of anxiety-like behaviors following 3AP.

Effects of short environmental enrichment on early-life adversity induced cognitive alternations in adolescent rats.

Early-life experiences, including parental care, affect cognitive performance later in life. Being exposed to early-life maternal separation (MS) increases susceptibility to stress-related psychopathology. Previous studies suggest that MS could induce learning and memory impairments. Since enriched environment (EE) provides more opportunities for exploration and social interaction, in the present study we evaluated the effects of a short EE paradigm with a duration of 13 days on cognitive abilities of maternally separated rats (MS; 180 min/day, postnatal day (PND) 1-21) during adolescence in four experimental groups: Control, Control+EE, MS, and MS+EE. Plasma corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels were also measured in experimental animals. We also studied the induction of long-term potentiation (LTP) in the slices of hippocampal CA1 area. The behavioral and electrophysiological assessments were started at PND 35. MS caused higher basal CORT levels in plasma and impaired spatial learning, memory, and social interaction. LTP induction was also impaired in MS rats and plasma BDNF levels were reduced in these animals. MS also induced more anxiety-like behavior. Short EE reduced plasma CORT levels had the potential to improve locomotor activity and anxiety-like behavior in MS+EE rats and reversed MS-induced impairments of spatial learning, memory, and social behavior. LTP induction and plasma BDNF levels were also enhanced in MS+EE rats. We concluded that short EE might be considered as a therapeutic strategy for promoting cognition.

Dimensional bias and adaptive adjustments in inhibitory control of monkeys.

Humans and macaque monkeys, performing a Wisconsin Card Sorting Test (WCST), show a significant behavioral bias to a particular sensory dimension (e.g. color or shape); however, lesions in prefrontal cortical regions do not abolish the dimensional biases in monkeys and, therefore, it has been proposed that these biases emerge in earlier stages of visual information processing. It remains unclear whether such dimensional biases are unique to the WCST, in which attention-shifting between dimensions are required, or affect other aspects of executive functions such as 'response inhibition' and 'error-induced behavioral adjustments'. To address this question, we trained six monkeys (Macaca mulatta) to perform a stop-signal task in which they had to inhibit their response when an instruction for inhibition was given by changing the color or shape of a visual stimulus. Stop Signal Reaction Time (SSRT) is an index of inhibitory processes. In all monkeys, SSRT was significantly shorter, and the probability of a successful inhibition was significantly higher, when a change in the shape dimension acted as the stop-cue. Humans show a response slowing following a failure in response inhibition and also adapt a proactive slowing after facing demands for response inhibition. We found such adaptive behavioral adjustments, with the same pattern, in monkeys' behavior; however, the dimensional bias did not modulate them. Our findings, showing dimensional bias in monkey, with the same pattern, in two different executive control tasks support the hypothesis that the bias to shape dimension emerges in early stages of visual information processing.

Pain influences food preference and food-related memory by activating the basolateral amygdala in rats.

The amygdala has been demonstrated to contribute to pain-related behavior and food preference. Here, the effect of pain on food preference and food-matched visual-cue memory, in the presence or absence of a basolateral amygdala (BLA) lesion, has been evaluated using a novel innovative apparatus and protocol. Forty adult male Wistar rats were randomly divided into five groups (n = 8) as follows: control, pain, ibuprofen + pain, BLA lesion, BLA lesion + pain groups. Bilateral lesions of the BLA were produced by passing a current of 1.5 mA for 7 s. Pain was induced on the right hind paw of the rats by sub-plantar injection of 50 µl of 2.5% formalin. The animals were encountered with four different meals including wholemeal, wholemeal + sugar, white flour, and biscuit. Each test session consisted of six trials with inter-trial intervals of 15 min. The number of visits to each meal zone and port, the amount of time spent in each food zone and port, traveled distance in each food zone, food consumption per each visit and the total food consumption were recorded. The control group showed a high biscuit preference and low white flour preference. Rats suffering BLA lesion and rats in the BLA lesion + pain group exhibited a shifted preference curve. They had a bias toward eating wholemeal + sugar rather than white flour and biscuit. This group also showed an impaired spatial memory. In conclusion, our findings suggest that the BLA may be involved in pain-induced food preference and food-matched visual-cue memory.

Focal unilateral mechanical lesion in barrel cortex impairs rat's abilities to discriminate textures.

PURPOSE/AIM OF THE STUDY: Whiskers are important sensory organs that play a key role in rodents' discriminative and exploration behaviours and unilateral injuries of the somatosensory cortex related to whisker barrel cortex can change the activity of neurons in the intact contralateral barrel cortex. We evaluated the effects of unilateral mechanical lesion of right barrel cortex on novel texture discrimination in behavioural test and neuronal responses of left barrel cortex. MATERIALS AND METHODS: Ten days after a unilateral mechanical lesion in the right barrel cortex, adult male rats were experimented regarding three paired different textures in novel texture discrimination test dependent on whiskers. In addition, responses of left barrel cortical neurons to controlled deflections of right whiskers were recorded using extracellular single-unit recordings technique. RESULTS: Data analysis showed that the discrimination ratio and preference indexes as criteria to find a novel texture significantly decreased in the lesion group compared to the intact rats (p < .05). In electrophysiological level, the barrel neural cortical spontaneous activity and the ON and OFF response magnitude of intact barrel cortex neurons in the lesion group decreased compared to the intact group (p < .05). CONCLUSIONS: The present study showed that unilateral mechanical lesion in the rats' barrel cortex cause a decrease in their abilities for discriminating textures, as well as, the anaesthetized rats whose response properties of intact barrel cortical area changed to whisker deflection, too. These changes can influence on the ability of rats to differentiate textures.

Color-hierarchies in executive control of monkeys' behavior.

Processing advantages for particular colors (color-hierarchies) influence emotional regulation and cognitive functions in humans and manifest as an advantage of the red color, compared with the green color, in triggering response inhibition but not in response execution. It remains unknown how such color-hierarchies emerge in human cognition and whether they are the unique properties of human brain with advanced trichromatic vision. Dominant models propose that color-hierarchies are formed as experience-dependent learning that associates various colors with different human-made conventions and concepts (e.g., traffic lights). We hypothesized that if color-hierarchies modulate cognitive functions in trichromatic nonhuman primates, it would indicate a preserved neurobiological basis for such color-hierarchies. We trained six macaque monkeys to perform cognitive tasks that required behavioral control based on colored cues. Color-hierarchies significantly influenced monkeys' behavior and appeared as an advantage of the red color, compared to the green, in triggering response inhibition but not response execution. For all monkeys, the order of color-hierarchies, in response inhibition and also execution, was similar to that in humans. In addition, the cognitive effects of color-hierarchies were not limited to the trial in which the colored cues were encountered but also persisted in the following trials in which there was no colored cue on the visual scene. These findings suggest that color-hierarchies are not resulting from association of colors with human-made conventions and that simple processing advantage in retina or early visual pathways does not explain the cognitive effects of color-hierarchies. The discovery of color-hierarchies in cognitive repertoire of monkeys indicates that although the evolution of humans and monkeys diverged in about 25 million years ago, the color-hierarchies are evolutionary preserved, with the same order, in trichromatic primates and exert overarching effects on the executive control of behavior.

The citrus flavanone naringenin prevents the development of morphine analgesic tolerance and conditioned place preference in male rats.

BACKGROUND: Opioids are effective analgesics in the management of chronic pain. However, their clinical use is hindered by adverse side effects such as addiction and analgesic tolerance. Naringenin is a common polyphenolic constituent of the citrus fruits and is one of the most commonly consumed flavonoids within our regular diet. However, its influences on opioid tolerance and addiction have not yet been clarified. OBJECTIVES: To examine the effect of different doses of naringenin on analgesic tolerance, conditioned place preference and neuroinflammation in morphine-exposed rats. METHODS: Analgesic tolerance was induced by the injection of 10 mg/kg morphine twice daily for 8 days in 70 male Wistar rats. To evaluate the effect of naringenin on the development of morphine tolerance, different doses (10, 25 and 50 mg/kg i.p.) were injected 15 min before morphine. The tail-flick test was used to assess nociceptive threshold. Conditioned place preference test was used to evaluate morphine-seeking behaviors. The lumbar spinal cord was assayed to determine glial fibrillary acidic protein (GFAP) and cyclooxygenase-2 (COX-2) levels by Western blotting. RESULTS: The data showed that naringenin could significantly prevent morphine tolerance (p < .001) and conditioned place preference. In addition, chronic morphine-induced GFAP and COX-2 overexpression was significantly reversed by 50 mg/kg naringenin (p < .05 and p < .01, respectively). CONCLUSION: Our results suggest that naringenin may have a potential anti-tolerant/anti-addiction property against chronic morphine misuse and that this preventive effect is associated with its anti-neuroinflammatory effects.

Resistance training-induced muscle hypertrophy is mediated by TGF-ß1-Smad signaling pathway in male Wistar rats.

The TGF-ß1-Smad pathway is a well-known negative regulator of muscle growth; however, its potential role in resistance training-induced muscle hypertrophy is not clear. The present study proposed to determine whether and how this pathway may be involved in resistance training-induced muscle hypertrophy. Skeletal muscle samples were collected from the control, trained (RT), control + SB431542 (CITGF ), and trained + SB431542 (RTITGF ) animals following 3, 5, and 8 weeks of resistance training. Inhibition of the TGF-ß1-Smad pathway by SB431542 augmented muscle satellite cells activation, upregulated Akt/mTOR/S6K1 pathway, and attenuated FOXO1 and FOXO3a expression in the CITGF group (all p < .01), thereby causing significant muscle hypertrophy in animals from the CITGF . Resistance training significantly decreased muscle TGF-ß1 expression and Smad3 (P-Smad3S423/425 ) phosphorylation at COOH-terminal residues, augmented Smad2 (P-Smad2-LS245/250/255 ) and Smad3 (P-Smad3-LSer208 ) phosphorylation levels at linker sites (all p < .01), and led to a muscle hypertrophy which was unaffected by SB431542, suggesting that the TGF-ß1-Smad signaling pathway is involved in resistance training-induced muscle hypertrophy. The effects of inhibiting the TGF-ß1-Smad signaling pathway were not additive to the resistance training effects on FOXO1 and FOXO3a expression, muscle satellite cells activation, and the Akt/mTOR/S6K1 pathway. Resistance training effect of satellite cell differentiation was independent of the TGF-ß1-Smad signaling pathway. These results suggested that the effect of the TGF-ß1-Smad signaling pathway on resistance training-induced muscle hypertrophy can be attributed mainly to its diminished inhibitory effects on satellite cell activation and protein synthesis. Suppressed P-Smad3S423/425 and enhanced P-Smad2-LS245/250/255 and P-Smad3-LSer208 are the molecular mechanisms that link the TGF-ß1-Smad signaling pathway to resistance training-induced muscle hypertrophy.

Sex differences in sleep and sleep loss-induced cognitive deficits: The influence of gonadal hormones.

Males and females can respond differentially to the same environmental stimuli and experimental conditions. Chronic sleep loss is a frequent and growing problem in many modern societies and has a broad variety of negative outcomes for health and well-being. While much has been done to explore the deleterious effects of sleep deprivation (SD) on cognition in both human and animal studies over the last few decades, very little attention has been paid to the part played by sex differences and gonadal steroids in respect of changes in cognitive functions caused by sleep loss. The effects of gonadal hormones on sleep regulation and cognitive performances are well established. Reduced gonadal function in menopausal women and elderly men is associated with sleep disturbances and cognitive decline as well as dementia, which suggests that sex steroids play a key role in modulating these conditions. Finding out whether there are sex differences in respect of the effect of insufficient sleep on cognition, and how neuroendocrine mediators influence cognitive impairment induced by SD could provide valuable insights into the best therapies for each sex. In this review, we aim to highlight the involvement of sex differences and gonadal hormone status on the severity of cognitive deficits induced by sleep deficiency in both human and animal studies.

Interaction of music and emotional stimuli in modulating working memory in macaque monkeys.

Background music is one of the most frequently encountered contextual factors that affect cognitive and emotional functions in humans. However, it is still unclear whether music induces similar effects in nonhuman primates. Answering this question might bring insight to the long-lasting question regarding the ability of nonhuman primates in perceiving and dissociating music from other nonmusical acoustic information. In the present study, macaque monkeys were trained to perform a working memory task that required matching visual stimuli. These stimuli had different emotional content (neutral, negative, and positive). Monkeys performed the task within different background acoustic conditions (music, same-intensity noise, and silence). We hypothesized that the auditory stimuli might interact with emotional information of visual stimuli and modulate monkeys' performance. Furthermore, if the effects of music and noise on monkeys' behavioral measures differ it would mean that monkeys perceived and processed music differently. We found that, monkeys committed more errors and were slower when they encountered stimuli with negative or positive emotional content. In the presence of music, the influence of emotional stimuli on monkeys' performance significantly differed from those of the neutral stimuli, however, in the presence of noise, the effects of emotional stimuli on monkeys' performance were not distinguishable. The dissociable effects of music and noise on monkeys' performance show that the effects of emotional stimuli were dependent on the background acoustic conditions. Our findings indicate that background music and the same-intensity noise were differentially perceived by monkeys and influenced their cognitive functions.

The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Cognitive impairments occurs in MS patients including learning and memory impairments. More than 50% of MS patients suffer from sleep problems. It has been suggested that in animal models exercise has direct neuroprotective effects on MS and sleep deprivation (SD). In this research, MS impairments were induced using a demyelination model as an indicator of MS disease. Also induction of SD was done using multiple platform. In order to focus on the research question, combination of MS model with SD was studied. In this study, the impact of treadmill exercise on learning and memory impairments was investigated. Material and methods: Male wistar rats were used in the present study. Exercise groups exercised daily for 1 h/day for 10 consecutive days with treadmill (speed: 18 m/min and inclination: 25°). The multiple platform method was applied for the induction of a 72 h SD. The cognitive functions were evaluated using Morris water maze (MWM) and open field tests. Animals were anaesthetized with a certain dose of ketamine and xylazin. After full anesthesia, the rat was placed on rat stereotaxic instrument in the skull-flat position. Demyelination was induced bilaterally by direct single injection of 3 µl of 0.01% ethidium bromide in sterile 0.9% saline at the rate of 1 µl/min into the hippocampal formation. The dose was injected using appropriate stereotaxic coordinates. Results: All of the learning and memory indices in the MWM task showed that SD and hippocampal demyelination destroy learning and memory. It seems that exercise can modulate the destructive effects of SD and demyelination on learning and memory at the behavioral level.

Heterogeneous effects of cholecystokinin on neuronal response properties in deep layers of rat barrel cortex.

Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In this study, we investigated the effects of CCK-8s and LY225910 (CCK2 receptor antagonist) on properties of neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. This study was done on 20 male Wistar rats, weighing 230-260 g. CCK-8s (300 nmol/rat) and LY225910 (1 µmol/rat) were administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in the barrel cortex using tungsten microelectrodes. Computer controlled mechanical displacement was used to deflect whiskers individually or in combination at 30 ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interaction. ICV administration of CCK-8s and LY225910 had heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to PW and/or AW deflections, and CTR for both ON and OFF responses. The results of this study demonstrated that CCK-8s can modulate neuronal response properties in deep layers of rat barrel cortex probably via CCK2 receptors.

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties.

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.