Opiates and dopamine （DA） play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and...Opiates and dopamine （DA） play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus （WGTA） delayed-response task. Morphine and DA agonists （SKF-38393, apomorphine and bromocriptine） or DA antagonists （SKF-83566, haloperidol and sulpiride） were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine （0.01 mg/kg） and apomorphine （0.01 or 0.06 mg/kg） co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.展开更多
In this study, the role of melanopsin-expressing retinal ganglion cells （mRGCs） in the glaucoma-induced depressive behavioral response pattern was investigated. The CFP-D2 transgenic glaucoma animal model from five ...In this study, the role of melanopsin-expressing retinal ganglion cells （mRGCs） in the glaucoma-induced depressive behavioral response pattern was investigated. The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study. Immunohistochemical labeling, quantitative analysis of mRGC morphology, open field test （OFT）, and statistical analysis were used. In comparison with C57 BL/6 mice, the age-matched CFP-D2 mice had significantly elevated intraocular pressure （lOP）. We observed parallel morphological changes in the retina, including a reduction in the density of cyan fluorescent protein- （CFP） expressing cells （cells mm^-2 at 2 months of age, 1309±26; 14 months, 878±30, P〈0.001）, mRGCs （2 months, 48_＋3; 14 months, 19±4, P〈0.001）, Brn3b-expressing RGCs （2 months, 1283±80; 14 months, 950±31, P〈0.001）, Brn-3b expressing mRGCs （5 months, 50.17%±5.5%; 14 months, 12.61%±3.8%, P〈0.001）, and reduction in the dendritic field size of mRGCs （mm^2 at 2 months, 0.077±0.015; 14 months, 0.065±0.015, P〈0.05）. CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled, number of entries into the center, and time spent in the center of the testing apparatus. The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs, most likely Brn-3b-positive mRGCs in CFP-D2 mice.展开更多
Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex.We tested the hypothesis that asynchronous stimulation of the two eyes might...Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex.We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input.Experiments on normal adults showed that repetitive brief exposure of grating stimuli,with the onset of each stimulus delayed by 8.3 ms in one eye,results in a shift in perceptual eye dominance.Clinical studies(Clinical trial registration number:Chi CTR2100049130),using popular 3D movies with similar asynchrony between the two eyes(amblyopic eye stimulated first)to treat anisometropic amblyopia,established that just 10.5 h of conditioning over<3 weeks produced improvement that met criteria for successful treatment.The benefits of asynchronous conditioning accumulate over 20–3045 min sessions,and are maintained for at least 2 years.Finally,we demonstrate that asynchronous binocular treatment alone is more effective than patching only.This novel treatment is popular with children and is some 50 times more efficient than patching alone.展开更多
The amygdala is a limbic structure that is involved in many brain functions, including emotion, learning and memory. It has been reported that melanopsin-expressing retinal ganglion cells(ip RGCs) innervate the medial...The amygdala is a limbic structure that is involved in many brain functions, including emotion, learning and memory. It has been reported that melanopsin-expressing retinal ganglion cells(ip RGCs) innervate the medial amygdala(Me A). However, whether conventional RGCs(c RGCs) project to the Me A remains unknown. The goal of this study was to determine if c RGCs project to the Me A and to determine the morphological properties of Me A-projecting RGCs(Me A-RGCs). Retrogradely labeled RGCs in whole-mount retinas were intracellularly injected to reveal their dendritic morphologies. Immunohistochemical staining was performed to selectively label ip RGCs(Me A-ip RGCs) and c RGCs(Me A-c RGCs). The results showed that 95.7% of the retrogradely labeled cells were c RGCs and that the rest were ip RGCs. Specifically, Me A-c RGCs consist of two morphological types. The majority of them exhibit small but dense dendritic fields and diffuse ramification patterns as previously reported in RG_(B2)(95%), while the rest exhibit small but sparse dendritic branching patterns resembling those of RG_(B3) cells(5%). Me Aip RGCs consist of M1 and M2 subtypes. The Me A-RGCs showed an even retinal distribution patterns. The soma and dendritic field sizes of the Me A-RGCs did not vary with eccentricity. In conclusion, the present results suggest that Me A-RGCs are structurally heterogeneous. These direct RGCs that input to the Me A could be important for regulating amygdala functions.展开更多
In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be di...In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.展开更多
基金supported by the National Basic Research Development Program(973program)of China(2012CB825500,2011CB707800)Basic Research Frontier Project of Chinese Academy of Sciences,China(KSCX2-EW-J-23)+1 种基金National Natural Science Foundation of China(31271167,31271168,81271495,31070963,31070965)Strategic Priority Research Program of the Chinese Academy of Science(XDB02020500)
文摘Opiates and dopamine （DA） play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus （WGTA） delayed-response task. Morphine and DA agonists （SKF-38393, apomorphine and bromocriptine） or DA antagonists （SKF-83566, haloperidol and sulpiride） were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine （0.01 mg/kg） and apomorphine （0.01 or 0.06 mg/kg） co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.
基金supported by the National Basic Research Program of China (2009CB320900 to Pu MingLiang,2011CB510206 to Pu MingLiangand Gao Jie)National Natural Science Foundation of China(30831160516 to Pu MingLiang)+2 种基金NIH EY04067 (N.C. Brecha)VAMerit Review (N.C. Brecha).supported by a summer fellowship from the PKU-UCLA Joint Research Institute
文摘In this study, the role of melanopsin-expressing retinal ganglion cells （mRGCs） in the glaucoma-induced depressive behavioral response pattern was investigated. The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study. Immunohistochemical labeling, quantitative analysis of mRGC morphology, open field test （OFT）, and statistical analysis were used. In comparison with C57 BL/6 mice, the age-matched CFP-D2 mice had significantly elevated intraocular pressure （lOP）. We observed parallel morphological changes in the retina, including a reduction in the density of cyan fluorescent protein- （CFP） expressing cells （cells mm^-2 at 2 months of age, 1309±26; 14 months, 878±30, P〈0.001）, mRGCs （2 months, 48_＋3; 14 months, 19±4, P〈0.001）, Brn3b-expressing RGCs （2 months, 1283±80; 14 months, 950±31, P〈0.001）, Brn-3b expressing mRGCs （5 months, 50.17%±5.5%; 14 months, 12.61%±3.8%, P〈0.001）, and reduction in the dendritic field size of mRGCs （mm^2 at 2 months, 0.077±0.015; 14 months, 0.065±0.015, P〈0.05）. CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled, number of entries into the center, and time spent in the center of the testing apparatus. The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs, most likely Brn-3b-positive mRGCs in CFP-D2 mice.
基金supported by the National Basic Research Program of China(2011CB510206,2015CB351806)the National Natural Science Foundation of China(31170986,31571091)Beijing Municipal Science&Technology Commission(Z151100000915070)。
文摘Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex.We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input.Experiments on normal adults showed that repetitive brief exposure of grating stimuli,with the onset of each stimulus delayed by 8.3 ms in one eye,results in a shift in perceptual eye dominance.Clinical studies(Clinical trial registration number:Chi CTR2100049130),using popular 3D movies with similar asynchrony between the two eyes(amblyopic eye stimulated first)to treat anisometropic amblyopia,established that just 10.5 h of conditioning over<3 weeks produced improvement that met criteria for successful treatment.The benefits of asynchronous conditioning accumulate over 20–3045 min sessions,and are maintained for at least 2 years.Finally,we demonstrate that asynchronous binocular treatment alone is more effective than patching only.This novel treatment is popular with children and is some 50 times more efficient than patching alone.
基金supported by the National Nature Science Foundation of China(81401102 to Liju Luan)National Nature Science Foundation of China(31571091 to Mingliang Pu)the National Basic Research Program of China(2016CB351806 to Mingliang Pu)
文摘The amygdala is a limbic structure that is involved in many brain functions, including emotion, learning and memory. It has been reported that melanopsin-expressing retinal ganglion cells(ip RGCs) innervate the medial amygdala(Me A). However, whether conventional RGCs(c RGCs) project to the Me A remains unknown. The goal of this study was to determine if c RGCs project to the Me A and to determine the morphological properties of Me A-projecting RGCs(Me A-RGCs). Retrogradely labeled RGCs in whole-mount retinas were intracellularly injected to reveal their dendritic morphologies. Immunohistochemical staining was performed to selectively label ip RGCs(Me A-ip RGCs) and c RGCs(Me A-c RGCs). The results showed that 95.7% of the retrogradely labeled cells were c RGCs and that the rest were ip RGCs. Specifically, Me A-c RGCs consist of two morphological types. The majority of them exhibit small but dense dendritic fields and diffuse ramification patterns as previously reported in RG_(B2)(95%), while the rest exhibit small but sparse dendritic branching patterns resembling those of RG_(B3) cells(5%). Me Aip RGCs consist of M1 and M2 subtypes. The Me A-RGCs showed an even retinal distribution patterns. The soma and dendritic field sizes of the Me A-RGCs did not vary with eccentricity. In conclusion, the present results suggest that Me A-RGCs are structurally heterogeneous. These direct RGCs that input to the Me A could be important for regulating amygdala functions.
基金supported by the National Natural Science Foundation of China(Grant No.31470987)the National Basic Research Development Program of China(Grant No.2015CB351800)“985”grants from Peking University for Physiological Psychology and China Postdoctoral Science Foundation(Grant No.2016M601066)
文摘In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.
