دسترسی یکساله به بیش از ۵۰۰ ژورنال روز جهان موجود در سامانه
-
http://medilib.ir
- ﻣﺪﺕ ﺯﻣﺎﻥ : 365 ﺭﻭﺯ
قیمت : 3,800,000 تومان- قیمت ویژه : 1,900,000تومان
Effects of postnatal ethanol exposure and maternal separation on mood, cognition and hippocampal arborization in adolescent rats
Claudia DanieleBiancoa1Ian CarlosHübnera1BiancaBennemannbCristiane Ribeirode CarvalhoaPatricia S.Brocardoab
doi : 10.1016/j.bbr.2021.113372
Volume 411, 6 August 2021, 113372
Ethanol exposure and early life stress during brain development are associated with an increased risk of developing psychiatric disorders. We used a third-trimester equivalent model of fetal alcohol spectrum disorders combined with a maternal separation (MS) protocol to evaluate whether these stressors cause sexually dimorphic behavioral and hippocampal dendritic arborization responses in adolescent rats. Wistar rat pups were divided into four experimental groups: 1) Control; 2) MS (MS, for 3 h/day from postnatal (PND) 2 to PND14); 3) EtOH (EtOH, 5 g/kg/day, i.p., PND2, 4, 6, 8, and 10); 4) EtOH + MS. All animals were divided into two cohorts and subjected to a battery of behavioral tests when they reached adolescence (PND37?44). Animals from cohort 1 were submitted to: 1) the open field test; 2) self-cleaning behavior (PND38); and 3) the motivation test (PND39?41). Animals from cohort 2 were submitted to: 1) the novel object recognition (PND37?39); 2) social investigation test (PND40); and 3) Morris water maze test (PND41?44). At PND45, the animals were euthanized, and the brains were collected for subsequent dendritic analysis. Postnatal ethanol exposure (PEE) caused anxiety-like behavior in females and reduced motivation, and increased hippocampal dendritic arborization in both sexes. MS reduced body weight, increased locomotor activity in females, and increased motivation, and hippocampal dendritic arborization in both sexes. We found that males from the EtOH + MS groups are more socially engaged than females, who were more interested in sweets than males. Altogether, these data suggest that early life adverse conditions may alter behavior in a sex-dependent manner in adolescent rats.
A biopsychosocial perspective on maternal parenting in the first two years of infant life
QiongWu
doi : 10.1016/j.bbr.2021.113375
Volume 411, 6 August 2021, 113375
Guided by a biopsychosocial perspective of mothering, this study investigated the interplay among biological (maternal cortisol reactivity), psychological (maternal depressive symptoms), and social (infant emotion and regulation) factors in contributing to early changes in maternal parenting. Participants were 1292 low-income, mother-infant pairs, assessed when the infants were 6-months (T1), 15-months (T2), and 24-months old (T3). Maternal parenting was observed at all assessment points. At T1, infant emotion expression and orienting towards mothers were observed, when maternal cortisol reactivity was assessed. Mothers reported their depressive symptoms at T1. Exploratory factor analysis revealed two parenting factors across time points: positive engagement and negative intrusiveness. Second-order latent growth curve models revealed interactions among maternal cortisol reactivity, depressive symptoms, and child negative emotion/orienting at T1 in predicting intercepts and slopes of two parenting factors. T1 maternal cortisol reactivity was associated with a higher positive engagement intercept for infants having high negative emotion at T1, but a lower positive engagement intercept for infants with low negative emotion at T1, under low T1 maternal depressive symptoms. T1 maternal cortisol reactivity was also related to a lower negative intrusiveness intercept for infants showing high orienting at T1. Longitudinally, maternal cortisol reactivity at T1 predicted a faster decline in positive engagement when infants showed high negative emotion at T1, but a slower decline when infants were less negative at T1. This study reveals a bivalent adaptation process in maternal sensitivity and enhances the current understanding of how biopsychosocial factors contribute to maternal parenting in low-income families.
Brain structural plasticity in visual and sensorimotor areas of airline pilots: A voxel-based morphometric study
ChuanyaQiuab1ChunyuZhaoc1GangHudYongZhangbYuyangZhucXinhuaiWudLubinWangc
doi : 10.1016/j.bbr.2021.113377
Volume 411, 6 August 2021, 113377
Airline pilot is a highly specialized profession that requires to response quickly and accurately in the presence of a wide variety of visual information. Although functional imaging studies have employed virtual simulation to identify brain areas that underlie various flying-related tasks, little is known about the specific patterns of structural plasticity in the airline pilot’s brain.
Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147
XiaoyuPana1LingChenb1WenXucShihuiBaoaJunWangaXiaoCuiaShichaoGaodKaipingLiucShivaniAvasthidMeixiZhangeRuijieChena
doi : 10.1016/j.bbr.2021.113374
Volume 411, 6 August 2021, 113374
Major depressive disorder (MDD) is a severe mental disorder, which is closely related to the deficiency of monoamine neurotransmitters. Our previous study suggested that acute treatment with J147, a novel curcumin derivative, produced antidepressant-like effects in mouse model of depression by regulation of 5-HT receptor subtypes. However, it is still unknown whether the antidepressant-like effects of J147 are involved in activation of central monoaminergic system. In this study, a series of classical behavior tests were employed to assess the involvement of monoaminergic system in antidepressant- and anxiolytic-like effects after sub-acute treatment of mice with J147 for 3 days. The results suggested that J147 at 10 mg/kg significantly reduced the immobility time in both the tail suspension and forced swimming tests, but didn’t show effects in the sucrose preference test. Similarly, sub-acute treatment of J147 did not induce amelioration in novelty suppressed feeding test. J147 increased duration and crossing time in the central area, but did not show significant change in rearing counts in the open field test. In neurochemical assays, studies suggested that serotonin and noradrenaline levels were significantly increased in the frontal cortex and hippocampus after treatment of J147 by the high-performance liquid chromatography (HPLC) with an electrochemical detector. Moreover, J147-induced significant inhibition of monoamine oxidase A activity. These findings suggest that the antidepressant- and anxiolytic-like effects of J147 might be related to the monoaminergic system by the evidence that high dose of J147 inhibits monoamine oxidase (MAO)-A activity and increases synaptic monoamines in the mouse brain.
LPS tolerance prevents anxiety-like behavior and amygdala inflammation of high-fat-fed dams’ adolescent offspring
ArthurRocha-GomesabAmanda EscobarTeixeirabDalila Gomesde OliveirabCamilla Mainy OliveiraSantiagobcAlexandre Alvesda SilvabTania ReginaRiulbcAna Cristina RodriguesLacerdaaVanessa AmaralMendonçaaEtelRocha-VieiraaeHércules RibeiroLeitead1
doi : 10.1016/j.bbr.2021.113371
Volume 411, 6 August 2021, 113371
Maternal high-fat diets (HFD) can generate inflammation in the offspring's amygdala, which can lead to anxiety-like behaviors. Conversely, lipopolysaccharide (LPS) tolerance can reduce neuroinflammation in the offspring caused by maternal high-fat diets. This study evaluated the combination of LPS tolerance and high-fat maternal diet on amygdala’s inflammatory parameters and the anxiety-like behavior in adolescent offspring. Female pregnant Wistar rats received randomly a standard diet or a high-fat diet during gestation and lactation. On gestation days 8, 10, and 12, half of the females in each group were intraperitonially injected with LPS (0.1 mg.kg-1). After weaning, the male offspring (n = 96) were placed in individual boxes in standard conditions, and when 6 weeks-old, the animals underwent: Open-Field, Light/Dark Box, Elevated Plus-Maze, and Rotarod tests. When 50 days-old the offspring were euthanized and the amygdala removed for cytokine and redox status analysis. The offspring in the HFD group showed lower amygdala IL-10 levels, high IL-6/IL-10 ratio, and anxiety-like behaviors. These effects were attenuated in the HFD offspring submitted to LPS tolerance, which showed an anti-inflammatory compensatory response in the amygdala. Also, this group showed a higher activity of the enzyme catalase in the amygdala. In addition, receiving the combination of LPS tolerance and maternal HFD did not lead to anxiety-like behavior in the offspring. The results suggest that LPS tolerance attenuated amygdala inflammation through an anti-inflammatory compensatory response besides preventing anxiety-like behavior caused by the high-fat maternal diet.
Post-traumatic stress disorder increases pain sensitivity by reducing descending noradrenergic and serotoninergic modulation
J?dina S.VieiraabGuilherme R.de SouzaaBrunaKalil-CuttibAlexandreGiusti-PaivaabFabiana C.Vilelaab
doi : 10.1016/j.bbr.2021.113367
Volume 411, 6 August 2021, 113367
Exposure to stress might influence pain sensitivity; however, little is known about whether post-traumatic stress disorder (PTSD)-like symptoms alter pain sensitivity and how it can happen. Male rats were exposed to the inescapable footshock paired with either social isolation or a control condition (not exposed to footshock but subjected to social isolation). After 7, 14, or 21 days, memory retention was evaluated. In the following three days, animals underwent the following tests: open-field, social interaction and formalin tests. Another group of animals were subjected to the object recognition test and to von Frey filaments. In other cohorts of animals, saline, fluoxetine, or desipramine were injected intrathecally and immunohistochemistry was performed to investigate whether PTSD-like symptoms alter the expression of c-Fos in serotonergic and noradrenergic neurons. Inescapable footshock induced the development of PTSD-like symptoms. Animals with PTSD-like symptoms showed an increase in the number of flinches in the formalin test and a reduction in mechanical threshold in the von Frey test at both retention intervals. The social interaction was negatively correlated with the nociceptive response in the formalin test. Fluoxetine or desipramine prevented the nociceptive response to chemical stimulus in the formalin test. In addition, in animals with PTSD-like symptoms, there was a reduction in c-Fos expression in serotonergic and noradrenergic neurons. Our results are important for the association of increased sensitivity to pain as one of the clinical manifestations that are present in the development of PTSD, and a possible treatment for increased pain sensitivity in male individuals with PTSD.
Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors
JianXuaJohn J.MarshallaStephenKraniotisaToshihiroNomuraaYonglingZhuaAnisContractorab
doi : 10.1016/j.bbr.2021.113378
Volume 411, 6 August 2021, 113378
Autism is a neurodevelopmental disorder characterized by impaired social interactions and restricted and repetitive behaviors. Although group 1 metabotropic glutamate receptors (mGluRs), and in particular mGluR5, have been extensively proposed as potential targets for intervention in autism and other neurodevelopmental disorders, there has not been a comprehensive analysis of the effect of mGluR5 loss on behaviors typically assessed in autism mouse models thought to be correlates of behavioral symptoms of human disorders. Here we present a behavioral characterization of mice with complete or partial loss of mGluR5 (homozygous or heterozygous null mutations in Grm5 gene). We tested several autism related behaviors including social interaction, repetitive grooming, digging and locomotor behaviors. We found that digging and marble burying behaviors were almost completely abolished in mGluR5 ko mice, although self-grooming was not altered. Social interaction was impaired in ko but not in heterozygote (het) mice. In tests of locomotor activity and anxiety related behaviors, mGluR5 ko mice exhibited hyperactivity and reduced anxiety in the open field test but unexpectedly, showed hypoactivity in the elevated zero-maze test. There was no impairment in motor learning in the accelerating rotarod in both ko and het mutant. Together these results provide support for the importance of mGluR5 in motor and social behaviors that are specifically affected in autism disorders.
Nurr1 deficiency shortens free running period, enhances photoentrainment to phase advance, and disrupts circadian cycling of the dopamine neuron phenotype
Heath S.PartingtonJennifer MakenzieNutterJeffrey B.Eells
doi : 10.1016/j.bbr.2021.113347
Volume 411, 6 August 2021, 113347
Neurological and neuropsychiatric disorders, including addiction, schizophrenia, and Parkinson’s disease (PD), involve dysfunction in midbrain dopamine (DA) neurotransmission with severity of disease symptoms and progression associated with disrupted circadian rhythms. The nuclear transcription factor Nurr1, essential for DA neuron (DAN) development, survival, and maintenance, is also known to interact with circadian rhythm regulating clock proteins. In the Nurr1-null heterozygous (+/-) mice, a Nurr1 deficient model which reproduces some of the alterations in DA function found in schizophrenia and PD, we measured, using wheel-running activity, the free running period (tau) and photoperiod entrainment. Because Nurr1 has a role in regulating the DA phenotype, we also measured the circadian fluctuations in the number of DANs using tyrosine hydroxylase (TH) immunofluorescence. In Nurr1 +/- mice, tau was significantly shorter and entrainment to a 6 h earlier shift in the dark cycle was accelerated. The Nurr1 wild-type (+/+) mice cycled DAN numbers across time, with a significantly greater number (?2-fold increase) of DANs at zeitgeber time (ZT) 0 than ZT12. The +/- mice, however, did not cycle the DA phenotype, as no differences in DAN numbers were observed between ZT0 and ZT12. Additionally, the +/- mice had significantly fewer DANs at ZT0 but not at ZT12 as compared to +/+ mice. Based these data, circadian rhythms and fluctuations in the DA phenotype requires normal Nurr1 function. A better understanding is needed of the mechanisms regulating the DA phenotype and subsequent neurotransmission across the circadian cycle and how this is altered in circadian rhythm and DA neurotransmission-associated disorders.
Audiovisual working memory and association with resting-state regional homogeneity
YuanjunXieabYanyanLiaMuzhenGuancHaidanDuanaXiliangXuaPengFangd
doi : 10.1016/j.bbr.2021.113382
Volume 411, 6 August 2021, 113382
Multisensory processing is a prevalent research issue. However, multisensory working memory research has received inadequate attention. The present study aimed to investigate the behavioral performance of an audiovisual working memory task and its association with resting-state functional magnetic resonance imaging (fMRI) regional homogeneity (ReHo). A total of 128 healthy participants were enrolled in this study. The participants completed a modified Sternberg working memory task using complex auditory and visual objects as materials involved in different encoding conditions, including semantically congruent audiovisual, semantically incongruent audiovisual, and single modality of auditory or visual object encoding. Two subgroups received resting-state fMRI scans according to their behavioral performances. The results showed that the semantically congruent audiovisual object encoding sped up the later unisensory memory recognition in this task. Moreover, the high behavioral performance (response time, RT) group showed increased ReHo in the executive control network (ECN) and decreased ReHo in the default mode network (DMN) and saline network (SN). In addition, resting-state ReHo values in the ECN nodes (e.g., middle frontal gyrus and superior frontal gyrus) was correlated with RT. These findings suggested that semantically congruent audiovisual processing in working memory was superior to unisensory memory recognition and may be involved in the different functional networks such as ECN.
Connectome-based model predicts episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment
YaoZhuaFeifeiZangaQingWangaQianqianZhangaChangTanaShaokeZhangaTianjianHuaLingyuQiaShouyongXubQingguoRenaChunmingXiea
doi : 10.1016/j.bbr.2021.113387
Volume 411, 6 August 2021, 113387
To explore whether the whole brain resting-state functional connectivity (rs-FC) could predict episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment.
Characterization of the direct pathway in Dyt1 ?GAG heterozygous knock-in mice and dopamine receptor 1-expressing-cell-specific Dyt1 conditional knockout mice
FumiakiYokoiHuan-XinChen1JannethOleas2Mai TuDang3HongXingKelly M.DexterYuqingLi
doi : 10.1016/j.bbr.2021.113381
Volume 411, 6 August 2021, 113381
DYT1 dystonia is a movement disorder mainly caused by a trinucleotide deletion (?GAG) in DYT1 (TOR1A), coding for torsinA. DYT1 dystonia patients show trends of decreased striatal ligand-binding activities to dopamine receptors 1 (D1R) and 2 (D2R). Dyt1 ?GAG knock-in (KI) mice, which have the corresponding ?GAG deletion, similarly exhibit reduced striatal D1R and D2R-binding activities and their expression levels. While the consequences of D2R reduction have been well characterized, relatively little is known about the effect of D1R reduction. Here, locomotor responses to D1R and D2R antagonists were examined in Dyt1 KI mice. Dyt1 KI mice showed significantly less responsiveness to both D1R antagonist SCH 23390 and D2R antagonist raclopride. The electrophysiological recording indicated that Dyt1 KI mice showed a significantly increased paired-pulse ratio of the striatal D1R-expressing medium spiny neurons and altered miniature excitatory postsynaptic currents. To analyze the in vivo torsinA function in the D1R-expressing neurons further, Dyt1 conditional knockout (Dyt1 d1KO) mice in these neurons were generated. Dyt1 d1KO mice had decreased spontaneous locomotor activity and reduced numbers of slips in the beam-walking test. Dyt1 d1KO male mice showed abnormal gait. Dyt1 d1KO mice showed defective striatal D1R maturation. Moreover, the mutant striatal D1R-expressing medium spiny neurons had increased capacitance, decreased sEPSC frequency, and reduced intrinsic excitability. The results suggest that torsinA in the D1R-expressing cells plays an important role in the electrophysiological function and motor performance. Medical interventions to the direct pathway may affect the onset and symptoms of this disorder.
Interference of commissural connections through the genu of the corpus callosum specifically impairs sensorimotor gating
GuanxiuXiao1HuashunLi1XuHu1XiaojieNiuQiXuYouguangYangYanmeiTao
doi : 10.1016/j.bbr.2021.113383
Volume 411, 6 August 2021, 113383
White matter abnormalities in schizophrenic patients are characterized as regional tract-specific. Myelin loss at the genu of the corpus callosum (GCC) is one of the most consistent findings in schizophrenic patients across the different populations. We characterized the axons that pass through the GCC by stereotactically injecting an anterograde axonal tracing viral vector into the forceps minor of the corpus callosum in one hemisphere, and identified the homotopic brain structures that have commissural connections in the two hemispheres of the prefrontal cortex, including the anterior cingulate area, the prelimbic area, the secondary motor area, and the dorsal part of the agranular insular area, along with commissural connections with the primary motor area, caudoputamen, and claustrum. To investigate whether dysmyelination in these commissural connections is critical for the development of schizophrenia symptoms, we generated a mouse model with focal demyelination at the GCC by stereotactically injecting demyelinating agent lysolecithin into this site, and tested these mice in a battery of behavioral tasks that are used to model the schizophrenia-like symptom domains. We found that demyelination at the GCC influenced neither the social interest or mood state, nor the locomotive activity or motor coordination. Nevertheless, it specifically reduced the prepulse inhibition of acoustic startle that is a well-known measure of sensorimotor gating. This study advances our understanding of the pathophysiological contributions of the GCC-specific white matter lesion to the related disease, and demonstrates an indispensable role of interhemispheric communication between the frontal cortices for the top-down regulation of the sensorimotor gating.
HIF-1 ? may play a role in late pregnancy hypoxia-induced autism-like behaviors in offspring rats
WeiyuWangabJinghuaTangabMinZhongabJieChenabTingyuLiabYingDaiab
doi : 10.1016/j.bbr.2021.113373
Volume 411, 6 August 2021, 113373
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by various factors. The present study aimed to determine whether prenatal hypoxia can lead to ASD and the role of hypoxia-inducible factor-1? (HIF-1?) in this process. We constructed a prenatal hypoxia model of pregnant rats by piping nitrogen and oxygen mixed gas, with an oxygen concentration of 10 ± 0.5 %, into the self-made hypoxia chamber. Rats were subjected to different extents of hypoxia treatments at different points during pregnancy. The results showed that hypoxia for 6 h on the 17th gestation day is most likely to lead to autistic behavior in offspring rats, including social deficits, repetitive behaviors, and impaired learning and memory. The mRNA expression level of TNF-? also increased in hypoxia-induced autism group and valproic acid (VPA) group. Western blotting analysis showed increased levels of hypoxia inducible factor 1 alpha (HIF-1?) and decreased levels of phosphatase and tensin homolog (PTEN) in the hypoxic-induced autism group. Meanwhile, N-methyl d-aspartate receptor subtype 2 (NR2A) and glutamate ionotropic receptor AMPA type subunit 2 (GluR2) were upregulated in the hypoxic-induced autism group. HIF-1? might play a role in hypoxia-caused autism-like behavior and its regulatory effect is likely to be achieved by regulating synaptic plasticity.
Differential roles of prelimbic and anterior cingulate cortical region in the modulation of histaminergic and non-histaminergic itch
XuanLia1JuanYaoa1Ke-huiHucBingWuaJian-fengSuiaJieGaobGuang-yanWuaShu-leiLiua
doi : 10.1016/j.bbr.2021.113388
Volume 411, 6 August 2021, 113388
Itch is an unpleasant sensation that evokes a desire to scratch. Itch processing in the peripheral and spinal cord has been studied extensively, but the mechanism of itch in the central nervous system is still unclear. Anterior cingulate cortex (ACC) and prelimbic cortex (Prl), two subregions of the prefrontal cortex closely related to emotion and motivation, have been reported to be activated during itching in a series of functional imaging studies. However, the exact role of Prl and the differences between ACC and Prl in itch modulation remains unknown. To directly test the differential roles of ACC and Prl in itch processing, we chemogeneticlly inhibited the caudal ACC and Prl, respectively. We found that inhibition of caudal ACC reduced histaminergic but not non-histaminergic itch-induced scratching behaviors. In contrast, inhibition of Prl reduced both histaminergic and non-histaminergic itch-induced scratching behaviors. Our study provided direct evidence of Prl involvement in itch modulation and revealed the differential roles of caudal ACC and Prl in regulating histaminergic and non-histaminergic itch.
Effects of enriched environment on depression and anxiety-like behavior induced by early life stress: A comparison between different periods
HongfeiHuangabQiWangbXiaofengGuanaXiaZhangaYihanZhangaJinlongCaocXiaobaiLia
doi : 10.1016/j.bbr.2021.113389
Volume 411, 6 August 2021, 113389
Brain development is a prolonged process and it is sensitive to the environment during critical periods. Stress in early life is believed to increase vulnerability to depression, while enriched environment (EE) has beneficial effects on neural plasticity and depression. In this study, we compared the therapeutic effect of EE during different periods on early life stress-induced depression, and investigated the role of brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT) on the effect of EE. Plasma corticosterone level was also detected to evaluate the reactivity of hypothalamic-pituitary-adrenal axis.
Effects of propofol on sleep architecture and sleep–wake systems in rats
Xiao-FangYueaAi-ZhongWangbYi-PingHoucKunFanb
doi : 10.1016/j.bbr.2021.113380
Volume 411, 6 August 2021, 113380
Previous studies have shown that the synchronization of electroencephalogram (EEG) signals is found during propofol-induced general anesthesia, which is similar to that of slow-wave sleep (SWS). However, a complete understanding is lacking in terms of the characteristics of EEG changes in rats after propofol administration and whether propofol acts through natural sleep circuits. Here, we examined the characteristics of EEG patterns induced by intraperitoneal injection of propofol in rats. We found that high (10 mg/kg) and medium (5 mg/kg) doses of propofol induced a cortical EEG of low-frequency, high-amplitude activity with rare electromyographic activity and markedly shortened sleep latency. The high dose of propofol increased deep slow-wave sleep (SWS2) to 4 h, as well as the number of large SWS2 bouts (>480 s), their mean duration and the peak of the power density curve in the delta range of 0.75–3.25 Hz. After the medium dose of propofol, the total number of wakefulness, light slow-wave sleep (SWS1) and SWS2 episodes increased, whereas the mean duration of wakefulness decreased. The high dose of propofol significantly increased c-fos expression in the ventrolateral preoptic nucleus (VLPO) sleep center and decreased the number of c-fos-immunoreactive neurons in wake-related systems including the tuberomammillary nucleus (TMN), perifornical nucleus (PeF), lateral hypothalamic nucleus (LH), ventrolateral periaqueductal gray (vPAG) and supramammillary region (SuM). These results indicated that the high dose of propofol produced high-quality sleep by increasing SWS2, whereas the medium dose produced fragmented and low-quality sleep by disrupting the continuity of wakefulness. Furthermore, sleep-promoting effects of propofol are correlated with activation of the VLPO cluster and inhibition of the TMN, PeF, LH, vPAG and SuM.
Extracellular levels of glucose in the hippocampus and striatum during maze training for food or water reward in male rats
C.J.ScavuzzoaL.A.NewmanbP.E.GoldcD.L.Korolc
doi : 10.1016/j.bbr.2021.113385
Volume 411, 6 August 2021, 113385
Glucose potently enhances cognitive functions whether given systemically or directly to the brain. The present experiments examined changes in brain extracellular glucose levels while rats were trained to solve hippocampus-sensitive place or striatum-sensitive response learning tasks for food or water reward. Because there were no task-related differences in glucose responses, the glucose results were pooled across tasks to form combined trained groups. During the first 1?3 min of training for food reward, glucose levels in extracellular fluid (ECF) declined significantly in the hippocampus and striatum; the declines were not seen in untrained, rewarded rats. When trained for water reward, similar decreases were observed in both brain areas, but these findings were less consistent than those seen with food rewards. After the initial declines in ECF glucose levels, glucose increased in most groups, approaching asymptotic levels ?15?30 min into training. Compared to untrained food controls, training with food reward resulted in significant glucose increases in the hippocampus but not striatum; striatal glucose levels exhibited large increases to food intake in both trained and untrained groups. In rats trained to find water, glucose levels increased significantly above the values seen in untrained rats in both hippocampus and striatum. The decreases in glucose early in training might reflect an increase in brain glucose consumption, perhaps triggering increased brain uptake of glucose from blood, as evident in the increases in glucose later in training. The increased brain uptake of glucose may provide additional neuronal metabolic substrate for metabolism or provide astrocytic substrate for production of glycogen and lactate.
Metformin improved memory impairment caused by chronic ethanol consumption during adolescent to adult period of rats: Role of oxidative stress and neuroinflammation
ZahraBaradaranabcArefehVakilianabcMostafaZareabcMiladHashemzehidMahmoudHosseiniefHosseinDinpanahgFarimahBeheshtibc
doi : 10.1016/j.bbr.2021.113399
Volume 411, 6 August 2021, 113399
Adolescence is a crucial time for brain maturation. We investigated the protective effects of metformin (Met) on behavioral changes, oxidative stress, tumor necrosis factor alpha (TNF-?) and nitrite in adulthood induced by ethanol (Eth) consumption during adolescent to adult period of rats.
Resting-state functional connectivity associated with gait characteristics in people with Parkinson’s disease
Adam P.HorinaPeter S.MyersbKristen A.PickettcdGammon M.EarhartabeMeghan C.Campbellbf
doi : 10.1016/j.bbr.2021.113398
Volume 411, 6 August 2021, 113398
Parkinson’s disease (PD) is a movement disorder caused by dysfunction in the basal ganglia (BG). Clinically relevant gait deficits, such as decreased velocity and increased variability, may be caused by underlying neural dysfunction. Reductions in resting-state functional connectivity (rs-FC) between networks have been identified in PD compared to controls; however, the association between gait characteristics and rs-FC of brain networks in people with PD has not yet been explored. The present study aimed to investigate these associations.
Effects of intrastriatal injection of the dopamine receptor agonist SKF38393 and quinpirole on locomotor behavior in hemiparkinsonism rats
MengnanGuoa1TianyuXianga1MinLiaYueSunaShuangSunaDadianChenaQingmeiJiaaYuchuanLiaXiaomengYaobXiaojunWangcXiaoZhangdFengHeaMinWanga
doi : 10.1016/j.bbr.2021.113339
Volume 411, 6 August 2021, 113339
Dopamine (DA) in the striatum is essential to influence motor behavior and may lead to movement impairment in Parkinson's disease (PD). The present study examined the different functions of the DA D1 receptor (D1R) and DA D2 receptor (D2R) by intrastriatal injection of the D1R agonist SKF38393 and the D2R agonist quinpirole in 6-hydroxydopamine (6-OHDA)-lesioned and control rats. All rats separately underwent dose-response behavior testing for SKF38393 (0, 0.5, 1.0, and 1.5??g/site) or quinpirole (0, 1.0, 2.0, and 3.0??g/site) to determine the effects of the optimal modulating threshold dose. Two behavior assessment indices, the time of latency to fall and the number of steps on a rotating treadmill, were used as reliable readouts of motor stimulation variables for quantifying the motor effects of the drugs. The findings indicate that at threshold doses, SKF38393 (1.0??g/site) and quinpirole (1.0??g/site) produce a dose-dependent increase in locomotor activity compared to vehicle injection. The ameliorated behavioral responses to either SKF38393 or quinpirole in lesioned rats were greater than those in unlesioned control rats. Moreover, the dose-dependent increase in locomotor capacity for quinpirole was greater than that for SKF38393 in lesioned rats. These results can clarify several key issues related to DA receptors directly and may provide a basis for exploring the potential of future selective dopamine therapies for PD in humans.
Spontaneously Hypertensive Rat substrains show differences in model traits for addiction risk and cocaine self-administration: Implications for a novel rat reduced complexity cross
Kathleen M.KantakacCarissaStotsaElonMathiesonaCamron D.Bryantbc
doi : 10.1016/j.bbr.2021.113406
Volume 411, 6 August 2021, 113406
Forward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine self-administration traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated model traits for cocaine addiction risk and cocaine self-administration behaviors using a longitudinal within-subjects design. Impulsive-like and compulsive-like traits were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine use studied under fixed-ratio and tandem schedules of cocaine self-administration. Compulsive-like behavior correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the tandem schedule. Compulsive-like behavior also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22 %–40 % of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.
Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein
Daiane R.JanneraEmanuelle V.de LimabRachel T.da SilvabJulia R.ClarkebRafaelLindena
doi : 10.1016/j.bbr.2021.113386
Volume 411, 6 August 2021, 113386
The prion glycoprotein (PrPC) is highly expressed in the nervous system as well as in other organs. Its functional roles in behavior have been examined mainly in non co-isogenic, wild-type and PrPC-deficient mice, which showed both age- and genotype-dependent differences. In general, however, effects of genetic background upon behavioral tests are mostly unclear when applied to aging rodents. The present study aimed to determine the effect of deletion of the prion protein on behavior of isogenic mice across different ages. We disclosed a genotype-dependent behavioral dissociation between either motor or cognitive tests, as a function of both age and test type. Remarkably, we also detected a clear age- and genotype-dependent difference in the variability of performance in a cognitive test. The current findings are relevant for both the interpretation of PrPC-related behavior, as well as for issues of reproducibility in studies of rodent behavior.
Corrigendum to “Decision urgency invigorates movement in humans” [Behav. Brain Res. 382 (2020) (1–12) 112477]
DavidThura
doi : 10.1016/j.bbr.2021.113397
Volume 411, 6 August 2021, 113397
Incentive motivation: ‘wanting’ roles of central amygdala circuitry
Shelley M.WarlowaKent C.Berridgeb
doi : 10.1016/j.bbr.2021.113376
Volume 411, 6 August 2021, 113376
The central nucleus of amygdala (CeA) mediates positively-valenced reward motivation as well as negatively-valenced fear. Optogenetic or neurochemical stimulation of CeA circuitry can generate intense incentive motivation to pursue and consume a paired natural food, sex, or addictive drug reward, and even create maladaptive ‘wanting what hurts’ such as attraction to a shock rod. Evidence indicates CeA stimulations selectively amplify incentive motivation (‘wanting’) but not hedonic impact (‘liking’) of the same reward. Further, valence flips can occur for CeA contributions to motivational salience. That is, CeA stimulation can promote either incentive motivation or fearful motivation, even in the same individual, depending on situation. These findings may carry implications for understanding CeA roles in neuropsychiatric disorders involving aberrant motivational salience, ranging from addiction to paranoia and anxiety disorders.
Cell-type diversity in the bed nucleus of the stria terminalis to regulate motivated behaviors
Maria M.Ortiz-JuzaabRizk A.AlghoraziaJoseRodriguez-Romagueraacde
doi : 10.1016/j.bbr.2021.113401
Volume 411, 6 August 2021, 113401
Over the past few decades, the bed nucleus of the stria terminalis (BNST) gained popularity as a unique brain region involved in regulating motivated behaviors related to neuropsychiatric disorders. The BNST, a component of the extended amygdala, consists of a variety of subnuclei and neuronal ensembles. Multiple studies have highlighted the BNST as playing a fundamental role in integrating information by interfacing with other brain regions to regulate distinct aspects of motivated behaviors associated with stress, anxiety, depression, and decision-making. However, due to the high molecular heterogeneity found within BNST neurons, the precise mechanisms by which this region regulates distinct motivational states remains largely unclear. Single-cell RNA sequencing data have revealed that the BNST consists of multiple genetically identifiable cell-type clusters. Contemporary tools can therefore be leveraged to target and study such cell-types and elucidate their precise functional role. In this review, we discuss the different subsets of neurons found in the BNST, their anatomical distribution, and what is currently known about BNST cell-types in regulating motivated behaviors.
Valence encoding in the amygdala influences motivated behavior
Dana M.SmithabMary M.Torregrossaab
doi : 10.1016/j.bbr.2021.113370
Volume 411, 6 August 2021, 113370
The amygdala is critical for emotional processing and motivated behavior. Its role in these functions is due to its processing of the valence of environmental stimuli. The amygdala receives direct sensory input from sensory thalamus and cortical regions to integrate sensory information from the environment with aversive and/or appetitive outcomes. As many reviews have discussed the amygdala’s role in threat processing and fear conditioning, this review will focus on how the amygdala encodes positive valence and the mechanisms that allow it to distinguish between stimuli of positive and negative valence. These findings are also extended to consider how valence encoding populations in the amygdala contribute to local and long-range circuits including those that integrate environmental cues and positive valence. Understanding the complexity of valence encoding in the amygdala is crucial as these mechanisms are implicated in a variety of disease states including anxiety disorders and substance use disorders.
Toward a holistic view of value and social processing in the amygdala: Insights from primate behavioral neurophysiology
Philip T.PutnamaSteve W.C.Changabc
doi : 10.1016/j.bbr.2021.113356
Volume 411, 6 August 2021, 113356
Located medially within the temporal lobes, the amygdala is a formation of heterogenous nuclei that has emerged as a target for investigations into the neural bases of both primitive and complex behaviors. Although modern neuroscience has eschewed the practice of assigning broad functions to distinct brain regions, the amygdala has classically been associated with regulating negative emotional processes (such as fear or aggression), primarily through research performed in rodent models. Contemporary studies, particularly those in non-human primate models, have provided evidence for a role of the amygdala in other aspects of cognition such as valuation of stimuli or shaping social behaviors. Consequently, many modern perspectives now also emphasize the amygdala’s role in processing positive affect and social behaviors. Importantly, several recent experiments have examined the intersection of two seemingly autonomous domains; how both valence/value and social stimuli are simultaneously represented in the amygdala. Results from these studies suggest that there is an overlap between valence/value processing and the processing of social behaviors at the level of single neurons. These findings have prompted researchers investigating the neurophysiological mechanisms underlying social interactions to question what contributions reward-related processes in the amygdala make in shaping social behaviors. In this review, we will examine evidence, primarily from primate neurophysiology, suggesting that value-related processes in the amygdala interact with the processing of social stimuli, and explore holistic hypotheses about how these amygdalar interactions might be instantiated.
Learning safety to reduce fear: Recent insights and potential implications
MarkusFendtJudith C.KreutzmannTanjaJovanovic
doi : 10.1016/j.bbr.2021.113402
Volume 411, 6 August 2021, 113402
Fear of movement-related pain disturbs cortical preparatory activity after becoming aware of motor intention
MichihiroOsumiabMasahikoSumitanicYukiNishiaSatoshiNobusakoabBurcuDilekdeShuMoriokaab
doi : 10.1016/j.bbr.2021.113379
Volume 411, 6 August 2021, 113379
Fear of movement-related pain is known to disturb the process of motor preparation in patients with chronic pain. In the present study, we aimed to clarify the neural mechanisms underlying the influence of fear movement-related pain on motor preparatory brain activity using Libet’s clock and electroencephalography (EEG). Healthy participants were asked to press a button while watching a rotating Libet’s clock-hand, and report the number on the clock (“W time”) when they made the “decision” to press the button with their right index finger. Immediately after pressing the button, a painful electrical stimulus was delivered to the dorsum of the left hand, causing participants to feel fear of movement (button press-related pain). We found that fear of movement-related pain caused the W time to be early, and that the amplitudes of readiness potentials (RPs) increased after awareness of motor intention emerged. In addition, fear of movement-related pain caused over-activation of the medial frontal cortex, supplementary motor area, cingulate motor area, and primary motor cortex after participants became aware of their motor intention. Such over-activation might result from conflict between the unrealized desire to escape from a painful experience and motivation to perform a required motor task.
