The olfactory circuit of the fruit fly Drosophila melanogaster has emerged in recent years as an excellent paradigm for studying the principles and mechanisms of information processing in neuronal circuits. We discuss...The olfactory circuit of the fruit fly Drosophila melanogaster has emerged in recent years as an excellent paradigm for studying the principles and mechanisms of information processing in neuronal circuits. We discuss here the organizational principles of the olfactory circuit that make it an attractive model for experimental manipulations, the lessons that have been learned, and future challenges.展开更多
Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for th...Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.展开更多
Antidromic and orthodromic responses of the projection neurons in the dorsal horn ofthe spinal cord have been recorded by a glass microelectrode in anesthetized and paralyz-ed cats. Furthermore, the effect of cervical...Antidromic and orthodromic responses of the projection neurons in the dorsal horn ofthe spinal cord have been recorded by a glass microelectrode in anesthetized and paralyz-ed cats. Furthermore, the effect of cervical segment antidromic stimulation to orthodromicresponse of the projection neurons has been observed by way of conditioning-test stimulation. Among all the spinocervical tract neurons (SCT), the dorsal column postsynaptic neu-rons (DCPS) and the spinocervical tract-dorsal column postsynaptic neurons (SCT-DCPS),which were identified by cervical segment antidromic stimulation, 46% are low-thresholdmechanoreceptive (LTM) and 54% are wide-dynamic-range (WDR) neurons. Most LTMneurons can evoke the same response to both 10 times (10 T) and 50 times (50 T) the thresh-old stimulation on the peroneal nerve. Most WDR neurons to 50 T intensity stimulation arestronger than the 10 T stimulation. Under the antidromic-cervical segment conditioningstimulation, the amount of orthodromic-discharging in most WDR and few LTM neuronsreduced significantly. The result shows that both LTM and WDR projection neurons in the spinal cord canrespond to all peripheral Aβ fibers and part of the Aδ fibers; there are some inhibitionaldescending fibers which affect the projection neurons in the cervical segment dorsal col-umn and dorsolateral funiculi.展开更多
The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons(MSNs)comprise80%and 95%of striatal neurons in primat...The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons(MSNs)comprise80%and 95%of striatal neurons in primates and rodents,respectively.展开更多
In adult mammals, including humans, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyms (DG) show ongoing neurogenesis. Cerebral ischemic insults trigger neurogenes...In adult mammals, including humans, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyms (DG) show ongoing neurogenesis. Cerebral ischemic insults trigger neurogenesis from neural stem cells or progenitor cells located in the SVZ and DG. Newborn neurons are then functionally recruited into the circuitry of the CA1 region, striatum and DG granule cell layer.展开更多
Somato_visceral interaction or acupoint_visceral interaction is an important subject that greatly concerns scholars of both Chinese traditional and Western modern medicine. The role of our newly discovered spinal proj...Somato_visceral interaction or acupoint_visceral interaction is an important subject that greatly concerns scholars of both Chinese traditional and Western modern medicine. The role of our newly discovered spinal projection neurons and type A or C spinal ganglion neurons in convergence and integration of somato_visceral sensation is introduced. The possible challenge brought about by these related results onto some traditional concepts in neuroscience is also discussed.展开更多
Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallma...Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae (2 days before eclosion), overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.展开更多
Alternative stimulation of both the solitary tract nucleus (STN) and Hegu (HG) acupoint were made on the sodium pentobarbital anesthetized rats. The intracellular microelectrode recordings from the spinal drosal horn ...Alternative stimulation of both the solitary tract nucleus (STN) and Hegu (HG) acupoint were made on the sodium pentobarbital anesthetized rats. The intracellular microelectrode recordings from the spinal drosal horn of C5 - T1 segments were used to search and identify the spinal neurons. A total of 53 neurons responding to the stimulation of both STN and HG was recorded intracellularly. 24 and 29 of them were found to antidromically and synaptically respond to the stimulation of STN, respectively. These neurons were mainly distributed in the laminae III - Vl of spinal dorsal horn. The results indicate that (i) some spinal neurons can receive somatic afferent inputs from HG and convey them to the visceral sensory nucleus - STN; (ii) the other spinal neurons receive afferent impulse from both the STN and HG; (iii) the convergence and integration between somatic and visceral sensory inputs might occur in these spinal neurons and STN.展开更多
以成年雌性斑胸草雀为实验材料,利用膜片钳技术,探究埋植睾酮后RA(robust nucleus of the arcopallium)核团投射神经元电生理特性.研究结果显示:埋植组与正常雌鸟组相比,动作电位半宽显著减小,后超极化达峰值时间极显著缩短,膜输入阻抗...以成年雌性斑胸草雀为实验材料,利用膜片钳技术,探究埋植睾酮后RA(robust nucleus of the arcopallium)核团投射神经元电生理特性.研究结果显示:埋植组与正常雌鸟组相比,动作电位半宽显著减小,后超极化达峰值时间极显著缩短,膜输入阻抗显著减小,膜电容极显著增大.提示埋植睾酮后RA核团投射神经元的兴奋性提高,趋于雄性化.推测雄激素在一定程度上提高RA核团投射神经元兴奋性,进而使其长鸣趋于雄性化.展开更多
基金L. Liang has been supported by a Stanford Graduate Fellow-ship and a Lubert Stryer Stanford Interdisciplinary Graduate Fellowship. L. Luo is an investigator at the Howard Hughes Medical InstituteOlfaction research in our lab has been supported by NIH grant R01-DC005982
文摘The olfactory circuit of the fruit fly Drosophila melanogaster has emerged in recent years as an excellent paradigm for studying the principles and mechanisms of information processing in neuronal circuits. We discuss here the organizational principles of the olfactory circuit that make it an attractive model for experimental manipulations, the lessons that have been learned, and future challenges.
基金supported by the National Natural Science Foundation of China,Nos.32100899(to KZL),31830035(to FQX),31771156(to FQX),21921004(to FQX)the National Science and Technology Innovation 2030,No.2021ZD0201003(to FQX)+2 种基金the Key-Area Research and Development Program of Guangdong Province,No.2018B030331001(to FQX)the Strategic Priority Research Program of the Chinese Academy of Sciences,No.XDB32030200(to FQX)the Shenzhen Key Laboratory of Viral Vectors for Biomedicine,No.ZDSYS20200811142401005(to FQX)。
文摘Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.
基金Project supported by the National Natural Science Foundation of China.
文摘Antidromic and orthodromic responses of the projection neurons in the dorsal horn ofthe spinal cord have been recorded by a glass microelectrode in anesthetized and paralyz-ed cats. Furthermore, the effect of cervical segment antidromic stimulation to orthodromicresponse of the projection neurons has been observed by way of conditioning-test stimulation. Among all the spinocervical tract neurons (SCT), the dorsal column postsynaptic neu-rons (DCPS) and the spinocervical tract-dorsal column postsynaptic neurons (SCT-DCPS),which were identified by cervical segment antidromic stimulation, 46% are low-thresholdmechanoreceptive (LTM) and 54% are wide-dynamic-range (WDR) neurons. Most LTMneurons can evoke the same response to both 10 times (10 T) and 50 times (50 T) the thresh-old stimulation on the peroneal nerve. Most WDR neurons to 50 T intensity stimulation arestronger than the 10 T stimulation. Under the antidromic-cervical segment conditioningstimulation, the amount of orthodromic-discharging in most WDR and few LTM neuronsreduced significantly. The result shows that both LTM and WDR projection neurons in the spinal cord canrespond to all peripheral Aβ fibers and part of the Aδ fibers; there are some inhibitionaldescending fibers which affect the projection neurons in the cervical segment dorsal col-umn and dorsolateral funiculi.
基金supported by funding from the UK Medical Research Council,EU Framework Programme 7 Neurostemcell and Repair-HDBNA2015 Festival of NeuroscienceINTR12 2013
文摘The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons(MSNs)comprise80%and 95%of striatal neurons in primates and rodents,respectively.
文摘In adult mammals, including humans, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyms (DG) show ongoing neurogenesis. Cerebral ischemic insults trigger neurogenesis from neural stem cells or progenitor cells located in the SVZ and DG. Newborn neurons are then functionally recruited into the circuitry of the CA1 region, striatum and DG granule cell layer.
文摘Somato_visceral interaction or acupoint_visceral interaction is an important subject that greatly concerns scholars of both Chinese traditional and Western modern medicine. The role of our newly discovered spinal projection neurons and type A or C spinal ganglion neurons in convergence and integration of somato_visceral sensation is introduced. The possible challenge brought about by these related results onto some traditional concepts in neuroscience is also discussed.
基金supported by grants from the Department of Health of Heilongjiang Province, China (2006-228)the Educational Commission of Heilongjiang Province, China(11531096)+2 种基金the National Natural Science Foundation of China (31100819, 30970980)the Natural Science Foundation of Guangdong Province, China (S2011040002239)the China Postdoctoral Science Foundation (2010-0480805)
文摘Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae (2 days before eclosion), overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.
文摘Alternative stimulation of both the solitary tract nucleus (STN) and Hegu (HG) acupoint were made on the sodium pentobarbital anesthetized rats. The intracellular microelectrode recordings from the spinal drosal horn of C5 - T1 segments were used to search and identify the spinal neurons. A total of 53 neurons responding to the stimulation of both STN and HG was recorded intracellularly. 24 and 29 of them were found to antidromically and synaptically respond to the stimulation of STN, respectively. These neurons were mainly distributed in the laminae III - Vl of spinal dorsal horn. The results indicate that (i) some spinal neurons can receive somatic afferent inputs from HG and convey them to the visceral sensory nucleus - STN; (ii) the other spinal neurons receive afferent impulse from both the STN and HG; (iii) the convergence and integration between somatic and visceral sensory inputs might occur in these spinal neurons and STN.
文摘以成年雌性斑胸草雀为实验材料,利用膜片钳技术,探究埋植睾酮后RA(robust nucleus of the arcopallium)核团投射神经元电生理特性.研究结果显示:埋植组与正常雌鸟组相比,动作电位半宽显著减小,后超极化达峰值时间极显著缩短,膜输入阻抗显著减小,膜电容极显著增大.提示埋植睾酮后RA核团投射神经元的兴奋性提高,趋于雄性化.推测雄激素在一定程度上提高RA核团投射神经元兴奋性,进而使其长鸣趋于雄性化.