Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

脑电波定量指数、MRS影像学DLPFC代谢物指标与抑郁症严重程度的相关性及联合检测对抑郁症疗效的预测价值

目的探讨脑电波定量指数C3、T3、FP1、F3、F7各频段的(δ+θ)/(α+β)值及磁共振波谱(MRS)影像学双侧背外侧前额叶皮质(DLPFC)代谢物指标的胆碱(Cho)/肌酸(Cr)、N-乙酰天门冬氨酸(NAA)/Cr、肌醇(MI)/Cr比值与抑郁症严重程度的相关性及联合检测对抑郁症疗效的预测价值。方法选取郑州市第八人民医院2022年1月至2023年1月收治的236例抑郁症患者作为抑郁症组,依据病情严重程度分为轻、中、重度抑郁,另选同期236例健康体检者为对照组,均进行定量脑电图检查与MRS检查,比较两组脑电波定量指数C3、T3、FP1、F3、F7各频段的(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr、MI/Cr比值,分析各指标与抑郁症患者严重程度的相关性及各指标联合检测对抑郁症疗效的预测价值。结果抑郁症组各频段(δ+θ)/(α+β)值均高于对照组,轻度抑郁患者各频段(δ+θ)/(α+β)值<中度抑郁<重度抑郁(P<0.05);抑郁症组双侧DLPFC代谢物NAA/Cr低于对照组,Cho/Cr高于对照组,轻度抑郁患者NAA/Cr>中度抑郁>重度抑郁,轻度抑郁患者Cho/Cr<中度抑郁<重度抑郁(P<0.05);抑郁症严重程度与各频段(δ+θ)/(α+β)值、双侧Cho/Cr呈正相关,与双侧NAA/Cr呈负相关(P<0.05);有效抑郁症患者各频段(δ+θ)/(α+β)值、双侧Cho/Cr均小于无效患者,双侧NAA/Cr大于无效患者(P<0.05);脑电波定量指数各频段(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr联合检测预测抑郁症患者疗效的AUC为0.900。结论脑电波定量指数各频段(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr均与抑郁症患者严重程度密切相关,且联合检测对抑郁症疗效具有较高的预测价值。

Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury.All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University,China(approval No.XJTULAC2017-067)on August 26,2017.

Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study

The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.

Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats

Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.

Effects of Neonatal Undernutrition on Development of the Dorsolateral Prefrontal Cortex Pyramidal Cells in the Rat

The dorsolateral prefrontal cortex (dlPFC) of the rat plays a role in the encoding of neuronal signals involved in conflict-induced behavioral adjustment, working memory, planning and executive abilities, attentional control and other cognitive responses. In altricial species, early perinatal undernutrition interferes with the morphofunctional organization of a number of central nervous system (CNS) structures including the prefrontal cortex. The effects of neonatal undernutrition on dendritic arbor density, perikaryon measurements, and the number of spines (detected by rapid-Golgi) of basilar dendritic segments in layer III pyramidal neurons of the dlPFC were examined in male Wistar rats on postnatal (PDs) 12, 20, and 30. In the underfed (U) subjects the distal portions of the dendritic arbors had a consistent hipoplasia, mainly on PD 30, with reduced cross sectional area, perimeter, and spine densities on the basilar dendrites on all days studied. Thus, the alterations of the dlPFC pyramidal neurons may interfere with the plastic synaptic activity and cognitive performance of rats subjected to the stress of early underfeeding. Characterizing these anatomical alterations may help to understand the disrupted cognitive processes associated with neonatal undernutrition.

双相情感障碍与抑郁症DLPFC脑区转录组差异基因表达数据挖掘分析

目的:基于数据挖掘分析双相情感障碍(BD)与抑郁症背外侧前额叶皮质(DLPFC)转录组差异性分子表达,分析两者差异性基因相关通路及其与免疫、代谢的关系。方法:以“bipolar disorder”、“depression”、“sequencing”为关键词,在GEO数据库检索。从该基因库中分别提取6例对照和7例BD患者、29例对照和30例抑郁症患者的DLPFC转录组数据;240例健康对照和240例BD患者的外周血转录组数据,利用DESeq2软件计算差异表达基因,基于生物学过程(BP)采用GO功能分析、差异分析、交集分析的方法,分析2种疾病差异性基因相关通路及其与免疫、代谢的关系。结果:BD患者DLPFC脑区显著高表达基因总共有384个,显著低表达基因总共有117个。抑郁症患者DLPFC脑区显著高表达基因总共有165个,显著低表达基因总共有316个。BD患者和抑郁患者的脑区与正常对照相比都会发生神经系统的异常,而抑郁多富集免疫炎症相关通路,BD多富集在代谢相关通路。基因交集结果显示,抑郁患者差异基因中有74个免疫相关基因和20个代谢相关基因;而BD患者差异基因中有42个免疫相关基因和51个代谢相关基因。BD患者DLPFC脑区、外周血存在着51个与代谢相关差异性基因,外周血转录组数据验证代谢通路富集结果显示脂肪酸生物合成、泛醌等萜醌生物合成、硒化合物代谢、其他聚糖降解、其他类型的O.聚糖生物合成异常。结论:DLPFC转录组结果提示2种精神疾病在免疫、代谢相关功能的基因中发生异常比例不同,抑郁容易出现免疫相关异常,BD更容易出现代谢相关基因异常。

Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke.Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited.Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex,along with its subdivisions:anterior cingulate cortex,orbitofrontal cortex and dorsolateral prefrontal cortex.The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke.At 3 months poststroke,left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only(partial coefficient = 0.453,P = 0.045),after controlling for age,education,diabetes,neurological deficit,white matter lesions volume,as well as the location and volume of infarcts.At 15 months poststroke,there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test(partial coefficient = 0.661,P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test(partial coefficient = 0.573,P = 0.004) in female patients after the same adjustments.These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke.Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

Brain Activation in the Prefrontal Cortex during Motor and Cognitive Tasks in Adults

The prefrontal cortex (PFC) plays an important role in cognitive function, involved in Executive Functions (EFs) such as planning, working memory, and inhibition. Activation in the PFC also occurs during some motor activities. One commonly used tool to assess EF is the Tower of Hanoi, demonstrating sensitivity to PFC dysfunction. However, limited neuroimaging evidence is available to support the contribution of the PFC in the Tower of Hanoi task. In the current study, we use functional near infrared (fNIR) spectroscopy to examine hemodynamic responses associated with neural activity in the PFC in adults as they participate in the Tower of Hanoi task. We compared changes in cerebral oxygenation during resting, a motor task (tapping), and the Tower of Hanoi in 16 neurotypical adults, with measures of relative changes in concentration of oxygenated hemoglobin (Δoxy-Hb) and deoxygenated hemoglobin (Δdeoxy-Hb) taken throughout tasks, as well as total hemoglobin (ΔHbT) and oxygenation (Δoxy). Performance on the Tower of Hanoi was measured by the number of moves used to complete each level and the highest level of successful performance (3, 4, or 5 disks). We found a significant higher value of Δoxy-Hb and Δoxy in dorsolateral PFC (DLPFC) during the Tower of Hanoi as compared to tapping and resting. Significant changes in Δdeoxy-Hb and ΔHbT during the Tower of Hanoi were found in the right DLPFC only. These results support the notion that the Tower of Hanoi task requires higher levels of PFC activity than a similar motor task with low executive function demands.

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine(a marker of cell proliferation), c-Fos(a marker of cell viability) and NeuN(a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expression coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation(frequency, 30 Hz; current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes). In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1(OX1R) antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expression reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1 R expression were decreased, compared with that of the stimulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OX1R expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

Effects of nitric oxide on the prefrontal cortex in stressed rats

BACKGROUND:Nitric oxide (NO) exhibits both protective and detrimental effects in the central nervous system.OBJECTIVE:To investigate the effect of NO on the prefrontal cortex in neonatal stressed rats.DESIGN, TIME AND SETTING:A randomized, controlled, animal study was performed at the Anatomical Department of Iran University of Medical Sciences from May 2007 to August 2008.MATERIALS:Forty-eight male, Wistar rats were obtained from Pasteur's Institute, Tehran, Iran.METHODS:Rat stress models were established by immobilization and randomly received intraperitoneal injection of 2 mL physiological saline, L-arginine (200 mg/kg) as a NO precursor, N(G)-nitro-L-arginine methyl ester (20 mg/kg), or subcutaneous injection of 7-nitroindazole (25 mg/kg) as a NO synthase inhibitor.MAIN OUTCOME MEASURES:After the rats were treated for 4 weeks, the frontal cortex was harvested for histological observation and NO detection.RESULTS:Subcutaneous administration of N(G)-nitro-L-arginine methyl ester or 7-nitroindazole resulted in significantly lower prefrontal cortex thickness and NO production compared with subcutaneous administration of L-arginine (P<0.05).Prefrontal cortex thickness significantly increased in rats following L-arginine treatment, compared with physiological saline intervention (P<0.05).CONCLUSION:NO exhibited protective effects on the prefrontal cortex of stressed rats.

Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex,but not in the myocardium

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease.Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system.However,it is unknown whether the protein kinase C ε(PKCε)-aldehyde dehydrogenase 2(ALDH2) pathway is altered under chronic stress,and this study sought to address this question.A rat model of depression was established using a chronic unpredictable mild stress(CUMS) protocol.After experiencing CUMS for 4 weeks,the sucrose preference test and the forced swim test verified depressive-like behaviors.Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex,but was not altered in the myocardium.Western blot assays demonstrated reduced levels of ALDH2 and PKCε,but increased levels of 4-hydroxy-2-nonenal(4 HNE) adducts.Caspase-3 expression did not obviously alter,but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex.In the myocardium,expression of ALDH2,PKCε and 4 HNE adducts did not remarkably alter;while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated.Pearson's correlation test demonstrated that expression of 4 HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex,but not in the myocardium.In conclusion,chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex,but not in the myocardium.Moreover,4 HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

Altered functional connectivity of prefrontal cortex in chronic heroin abusers

In this study,we investigated alterations in the resting-state functional connectivity of the prefrontal cortex in chronic heroin abusers using functional magnetic resonance imaging.We found that,compared with normal controls,in heroin abusers the left prefrontal cortex showed decreased functional connectivity with the left hippocampus,right anterior cingulate,left middle frontal gyrus,right middle frontal gyrus and right precuneus.However,the right prefrontal cortex showed decreased functional connectivity with the left orbital frontal cortex and the left middle frontal gyrus in chronic heroin abusers.These alterations of resting-state functional connectivity in the prefrontal cortices of heroin abusers suggest that their frontal executive neural network may be impaired,and that this may contribute to their continued heroin abuse and relapse after withdrawal.

Neurochemical metabolites in the medial prefrontal cortex in bipolar disorder A proton magnetic resonance spectroscopy study

The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type Ⅰ and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.

Olanzapine Induces Inflammation and Immune Response via Activating ER Stress in the Rat Prefrontal Cortex

Objective Antipsychotics,in particular olanzapine,are first-line medications for schizophrenia.The prefrontal cortex(PFC)is an important region for antipsychotics’therapeutic effects.The PFC inflammatory and immune pathways are associated with schizophrenia pathogenesis.However,the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains unclear.We aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of rats.Since the inflammatory and immune pathways are related to endoplasmic reticulum(ER)stress,we further investigated whether or not olanzapine-induced inflammation and immune responses were related to ER stress.Methods Expression of pro-inflammatory markers including IkappaB kinaseβ(IKKβ),nuclear factor kappa B(NFκB),tumor necrosis factorα(TNF-α),interleukin-6(IL-6)and IL-1β,and immune-related proteins including inducible nitric oxide synthase(iNOS),toll-like receptor 2(TLR2)and cluster of differentiation 14(CD14)were examined by Western blotting.Results Olanzapine treatments for 1,8 and 36 days significantly activated the inflammatory IKKβ/NFκB signaling,and increased the expression of TNF-α,IL-6,IL-1βand immune-related proteins such as iNOS,TLR4 and CD14.Olanzapine treatment for 1 day,8 and 36 days also induced ER stress in the PFC.Co-treatment with an ER stress inhibitor,4-phenylbutyrate,inhibited olanzapine-induced inflammation and the immune response in the PFC.Conclusion These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia subjects.Olanzapine induces PFC inflammation and immune response,possibly via activating ER stress signaling.

Role of prefrontal cortex-nucleus accumbens glutamatergic projection in heroin reward and motivation

OBJECTIVE Glutamatergic projections from prefrontal cortex(PFc) to nucleus accumbens(NAc) regulate the dopamine(DA) release in NAc.However,it is not clear whether this circuit is effective for the reward and motivation of heroin addiction.Our study investigates the effects of metabotropic glutamate receptor 2/3(mGluR2/3) and the projections from ventromedial prefrontal cortex(vmPFc) to the NAc shell on the reward and motivation of heroin-addicted rats.METHODS First,rats were trained to selfadministration for 14 d.On the 15 thday,parts of rats were injected with mGluR 2/3 agonist LY379268(0.1,0.3 and 1.0 mg·kg-1,ip) systematically and another parts of rats were bilaterally microinjected with LY379268(0.3 and 1.0 g·L^(-1))at the volume of 0.5 μL into the ventral tegmental area(VTA),NAc core or NAc shell,respectively.All rats were followed by heroin self-administration testing under fixed ratio 1(FR1) schedule or progressed ratio(PR) schedule to observe the effect of LY379268 on the heroin reward or motivation.Second,rats were injected chemogenetic glutamatergic virus(pAAV-CaMKIIa-hM3 D(Gq)-mCherry or pAOV-CaMKIIa-hM4 D(Gi)-mCherry-3 Flag) or negative control virus in vmPFc,and trained to heroin self-administration for 14 d.On the 15 thday,rats were bilateral y microinjected with clozapine-N-oxide(CNO,1 mmol·L^(-1),0.5 μL) into NAc shell and tested the effect on the heroin reward or motivation.Finally,rats were injected optogenetical glutamatergic virus(AAV2/9-CaM KⅡ-hChR2-EYFP) or negative control virus in vmPFc,implanted 16 channel photoelectrode in ipsilateral NAc shell,and trained to heroin selfadministration for 14 d.On the 15 thday,rats were tested heroin reward under FR1 procedure with blue light stimulation in the wavelength of470 nm,frequency of 25 HZ and power of 5 mW.Each stimulation lasting for 1 h and interval for1 h.The spike changes before and after stimulation in NAc Shel neural nerve was recorded.RESULTS LY379268 cloud dose-dependent attenuated the heroin reward or motivation and the local effective site was mainly in the NAc shell.Chemogenetic results showed activation or inactivation the projection from vmPFc to NAc shell enhanced or attenuated the heroin reward and motivation,respectively.Optogenetical stimulation the same projection also enhanced the heroin reward,and a tonic neuronal firing at the nerve of NAc shell was observed during the light stimulation session.CONCLUSION mGluR2/3 activation in the NAc shell is involved in the inhibition of heroin reward and motivation.Activation the projection from PFc to NAc shell can enhance the effects on heroin reward and motivation.

Ritalin Dose Response Effect on Medial Prefrontal Cortex and on Animal Behavior

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC was dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects;however, most users were adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.

Right prefrontal cortex is activated for perceiving postural limits: a functional near-infrared spectroscopy study

The purpose of this study was to investigate neuronal mechanisms active during the percep-tion of forward postural limits in a standing po-sition and to specify fall-related brain activity using optical functional near-infrared spectros-copy. The study group included six right-handed, healthy female volunteers (range: 19, 20 years). The optical imaging device comprised 16 opto-des designed to provide 24-channel recording of changes in hemoglobin oxygenation. We meas-ured the changes of oxygenated hemoglobin levels in the frontal region when subjects per-ceived reachability in a standing position. Com- pared with those in other regions, the oxygen-ated hemoglobin levels in the right frontal region compatible with the right prefrontal cortex sig-nificantly increased. This result suggests that brain activities in the right prefrontal cortex are related to perception of reachability. Overesti-mation of postural limits has been reported as one of the risk factor for falling. This overesti-mation might be induced by dysfunction in the prefrontal cortex, resulting in a failure to inhibit a motor program that would have caused a loss of balance in reaching. Activation of the right prefrontal cortex may be a key factor for pre-venting accidental falls in the elderly and in pa-tients with neurological disorders.

Activation of Human Prefrontal Cortex to Pleasant and Aversive Taste Using Functional Near-Infrared Spectroscopy

The aim of the study was to investigate the representation of taste in human prefrontal cortex (PFC), in particular, to compare the representation of a pleasant and an aversive taste using functional near-infrared spectroscopy (fNIRS), so as to obtain further understanding of the taste preference mechanism. The pleasant stimulus used was sweet taste (10% sucrose), and the unpleasant stimulus was sour taste (1% critic acid). Based on event-related design, the experiments were performed with 16 healthy volunteers using the OEG-16 fNIRS sensor. A general linear model was used to analyze the collected data. For the concentration change of oxygenated hemoglobin (ΔoxyHb), we found that significant deactivation was induced by sweetness and sourness in parts of the frontopolar area, orbitofrontal area and dorsolateral prefrontal cortex in bilateral hemisphere of human brain. And the right PFC showed different levels of activation between sweetness and sourness. In addition, brain activities were more sensitive to sourness than sweetness. Finally, we confirmed that the PFC was involved in sweet and sour taste processing, and fNIRS provided an alternative way for studying taste-related brain function under more natural conditions.