Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s lifespan.The astrocytic regulation of neuronal activity has been increasingly recognized in recent years.Astroc...Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s lifespan.The astrocytic regulation of neuronal activity has been increasingly recognized in recent years.Astrocytes are now recognized as playing a more complex role than mere bystanders in the central nervous system.However,their role in regulating the sleep neurocircuitry is not well understood.From this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the hypothalamus.We briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.展开更多
A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior te...A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates.Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD,but its exact role in spatial memory is not well understood.The pathway arising from the postrhinal cortex(POR)and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway,the function of the pathway in spatialmemory is relatively unknown.To further illuminate the function of the UF in spatial memory,we dissected the POR–vlOFC pathway in mice.We determined that the POR–vlOFC pathway is a glutamatergic structure,and that glutamatergic neurons in the POR regulate spatial memory retrieval.We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval.These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory,as in MCI and AD.展开更多
BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tub...BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus （TMn）, with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE： To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING： Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS： Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups（n = 5）： control, ventrolateral preoptic area （VLPO） lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma （St. Louis, USA）. METHODS： Four electroencephalogram screw electrodes were implanted into the skull at a frontal region （two） and parietal bones （two） on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette （10–20 mm tip diameter） containing ibotenic acid solution （10 nmol/L） was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline （10 nmol/L）, a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES： Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit （Micro1 401 mk2） and Data collection software （Spike Ⅱ）. RESULTS： VLPO lesion induced an increased duration of wakefulness （W, 13.17%） and light slow-wave sleep （SWS1, 28.9%）, respectively. Deep slow-wave sleep （SWS2, 43.74%） and paradoxical sleep （PS, 44.07%） were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion （P 〈 0.01）. Microinjection of bicuculline into the TMn following VLPO lesion at 10：00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% （P 〈 0.01） and 50.97% （P 〈 0.01）, respectively. In addition, SWS2 and PS were decreased by 68.08% （P 〈 0.01） and 39.92% （P 〈 0.05）, respectively, compared with prior to VLPO lesion. CONCLUSION： The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive （sleepiness） via local circuit to directly inhibit histaminergic neurons.展开更多
Objective: To study the characteristics of the postsynaptic potentials in thoracic sympatheticpreganglionic neurons (SPNs) evoked by electrical stimulation of the rostral ventrolateral medulla (RVLM ) incats. Methods:...Objective: To study the characteristics of the postsynaptic potentials in thoracic sympatheticpreganglionic neurons (SPNs) evoked by electrical stimulation of the rostral ventrolateral medulla (RVLM ) incats. Methods: In 11 α--chloralose/urethane anesthetized, artificially ventilated cats, intracellular recordings weremade from T, spinal cord with microelectrodes filled with 3 mol/L KCl. SPNs were identified by antidromicstimulation of the T3 white ramus. Results: Twenty--four SPNs were recorded, the resting membrane potentials ofwhich ranged between -- 45 -- -- 90 mV. The onset latency and threshold of the antidromic action potentialsaveraged (6. 48 + 0. 89) ms and (2. 86 + 0. 37) V respectively. Single pulse (0. 2 ms. 50-- 300 PA) electricalstimulation of RVLM evoked fast excitatory postsynaptic potentials (eEPSPs) with short latencies (4--47 ms) inall the 24 SPNs. In 11 of the SPNs, EPSPs with longer latencies (IEPSPs, 70-- 140 ms) were also recorded. Mostof the eEPSPs and some of the IEPSPs were typical monosynaptic EPSPs as they were of constant onset latency.Conclusion: The results provided direct physiological evidence for that some RVLM sympathoexcitatory neuronsproject monosynaptically to thoracic SPNs. The descending pathways from RVLM may consist of two distinctgroups of fibers, the conduction velocities were calculated to be 5--25 m/s and 0. 78-- 1. 6 m/s respectively.展开更多
Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities ...Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson＇s disease （PD） and ET. Methods Thirty-six patients （PD： 20, ET： 16） were studied. Microelectrode recordings in the ventral oral posterior （Vop）and the ventral intermediate nucleus （Vim） of thalamus was performed on these patients who underwent thalamotomy.Electromyography （EMG） was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals （ISIs） were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis （K-W） test were used to compare the mean spontaneous firing rate （MSFR） of neurons of PD and ET patients. Results Three hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 （46.7%） tremor related neuronal activity, 74 neurons （22.9%） with tonic firing, and 98 （30.4%） neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 （24.6%） tremor-related neuronal activity, 77 （41.2%） neurons with tonic firing, and 64 neurons （34.2%） with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 （3.4-68.3） Hz （n=74） and that of neurons with irregular discharge （n=98） was 13.9 （3.0-58.1） Hz in PD; whereas MSFR of neurons with tonic firing （n=77） was 48.8 （19.0-135.5） Hz and that of neurons with irregular discharge （n=64） was 26.3 （8.7-84.7） Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET （K-W test, both P〈0.05）. Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET （16.3 Hz vs. 34.8 Hz, 28.0 Hz vs. 49.9 Hz） （K-W test, both P 〈0.05）, respectively. Conclusion In consistent with recent findings, the decreased MSFR of neurons observed in the Vop is likely to be involved in PD whereas the increased MSFR of neurons seen in the Vim may be a cause of ET.展开更多
Objective：To investigate the mechanism of the reversal effect of acupuncture on the fall of blood pressure induced by angiotensin （1-7）[Ang-（1 7）] in the caudal ventrolateral medulla （CVLM） of rats. Methods： A...Objective：To investigate the mechanism of the reversal effect of acupuncture on the fall of blood pressure induced by angiotensin （1-7）[Ang-（1 7）] in the caudal ventrolateral medulla （CVLM） of rats. Methods： Ang-（1-7） and its selective receptor antagonist （DAla7）, Ang（1-7） and Ang（779） were microinjected into the CVLM respectively to induce the change of blood pressure, during which, the concentrations of amino acid neurotransmitters were detected by means of microdialysis and high performance liquid chromatography （HPLC）combined with fluorescent detector, on the other hand, the effects of electro-acupuncture （EA） on the level of blood pressure and the concentrations of amino acid neurotransmitters were also observed. Results： Unilateral microinjection of Ang（1 7） into the CVLM could decrease the blood pressure （BP）, which was accompanied by an increase in the release of Glu and a decrease in the release of Tau in the same site; Whereas microinjection of Ang-779 into the CVLM could elevate BP, which was accompanied by a decrease in the release of Glu and an increase in the release of Tau; EA at acupoint Zusanli （ST 36） for 20 min could inhibit the fall of blood pressure induced by microinjection of Ang-（1-7） into the CVLM and the elevation of blood pressure induced by microinjection of Ang-779 into the CVLM, and in the meantime, it could inhibit the changes of the release of Glu and Tau induced by microinjection of Ang-（1-7） and Ang-779 into the CVLM. Conclusion： The reversal effect of EA on the fall or elevation of blood pressure induced by microinjection of Ang-（1-7） or Ang-779 into the CVLM might be related to the changes of Glu and Tau release.展开更多
ObjectiveTo observe the effects of pretreatment with electroacupuncture (EA) on neuron activity in the rostral ventrolateral medulla (RVLM) of rats with myocardial ischemia-reperfusion injury (MIRI) and explore the ce...ObjectiveTo observe the effects of pretreatment with electroacupuncture (EA) on neuron activity in the rostral ventrolateral medulla (RVLM) of rats with myocardial ischemia-reperfusion injury (MIRI) and explore the central regulatory mechanism of EA in attenuating MIRI.MethodsOf 72 SD rats, 12 were randomly allocated into the group of EA pretreatment + RVLM nucleus damage (EA + RVLM lesion group). The other 60 rats were randomized (20 rats each) into a sham-operation group, a model group, and an EA pretreatment group (EA group). Except for the rats in the sham-operation group, the models of MIRI were prepared by ligating the left anterior descending coronary artery in the model, EA, and EA + RVLM lesion groups. The rats of the EA group were intervened with EA at “Shénmén (神门HT7)” and “Tōnglĭ (通里HT5)”, 1 mA in current intensity and 2 Hz in frequency, for 20 min each time per day. Before modeling, the intervention was given for seven consecutive days. In the EA + RVLM lesion group, 3 weeks after microinjection with the neuronal apoptotic virus at bilateral RVLM, the same EA intervention as the EA group was provided. Afterward, the MIRI models were prepared. In the model group, no EA intervention was given. Using Powerlab electrophysiolograph, ST segment displacement value and arrhythmia score were recorded and analyzed before modeling, 30 min after ligation, and 120 min after reperfusion in each group. The concentration of cardiac troponin (cTnl) was detected with an ELISA assay kit. Using immunofluorescence staining, the expression level of c-fos protein of RVLM was detected in the sham-operation, model, and EA groups separately. Plexon multichannel acquisition processor was adopted to record the neuronal firing and field potential of RVLM in the sham-operation, model, and EA groups.ResultsST segment displacement value, arrhythmia score, and cTnl concentration 30 min after ligation and 120 min after reperfusion were all elevated in the model group compared to the sham-operation group (all P < 0.01). ST segment displacement value, arrhythmia score, and cTnl concentration were lower in the EA group compared to the model and EA + RVLM lesion groups (P < 0.01). Compared with the sham-operation group, the expression level of c-fos and the total firing frequency in RVLM were significantly higher in the model group (P < 0.01). However, the expression level of c-fos and the total firing frequency in RVLM were lower in the EA group compared with the model group (P < 0.01).ConclusionElectroacupuncture pretreatment may induce changes in c-fos protein expression and neuronal activity in RVLM to mitigate myocardial lesions. RVLM plays an important role in electroacupuncture pretreatment for alleviating MIRI.展开更多
The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors.Although the axons of deep cerebellar nuclei are known to project to primary tha...The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors.Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei,macroscopic investigation of the characteristics of these projections,such as the spatial distribution of recipient zones,is lacking.Here,we studied the output of the cerebellar interposed nucleus(IpN)to the ventrolateral(VL)and centrolateral(CL)thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing.We found that IpN stimulation induced mono-synaptic evoked potentials(EPs)in the VL but not the CL region.Furthermore,both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space.These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.展开更多
The nucleus tractus solitarii(NTS)is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity.Phenotypically-characterized NTS neurons have been im...The nucleus tractus solitarii(NTS)is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity.Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure(BP).Here,we investigated whether phenylethanolamine N-methyltransferase(PNMT)-expressing NTS(NTS^(PNMT))neurons contribute to the control of BP.We demonstrate that photostimulation of NTS^(PNMT)neurons has variable effects on BP.A depressor response was produced during optogenetic stimulation of NTS^(PNMT)neurons projecting to the paraventricular nucleus of the hypothalamus,lateral parabrachial nucleus,and caudal ventrolateral medulla.Conversely,photostimulation of NTS^(PNMT)neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia.In addition,genetic ablation of both NTS^(PNMT)neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex.Overall,we revealed the neuronal phenotype-and circuit-specific mechanisms underlying the contribution of NTS^(PNMT)neurons to the regulation of BP.展开更多
The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostr...The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the known that one of the mechanisms by which angiotensin II exerts cardiovascular reflexes within the brainstem. It is well- its effect is via the activation of pathways that generate reactive oxygen species （ROS）. In the central nervous system, ROS are reported to be involved in several pathological dis- eases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.展开更多
Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY...Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY) of 1-]2 weeks old and of both sexes. The systolic pressure (SP), in rats of 4-12 weeks old,increased with age and was signifficantly higher in SHR than WKY. In SHR, the increase was also significantly greater in male than female. The ir-Ang Ⅱ increased with age in all cardiovascular brain areas up to 12 weeks old in SHR, but only up to 4 weeks old in WKY. There was also sex difference in SHR. The changes in ir-Ang Ⅱ, particularly in the ventrolateral medulla (VLM), correlated well with changes in SP. The findings suggest thal interaction between brain Ang Ⅱ and cardiovascular brain areas, particularly the VLM and hypothalamus, may be crucial in the development of hypertension. The results also indicale sexual dimorphism in brain Ang Ⅱ in addition to blood pressure reaction in the developing SHR.展开更多
Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to ...Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion.While both basal ganglia and thalamus have tremor activity,the thalamus appears to play a more important role in tremor production,and basal ganglia β oscillatory activity might be the trigger.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(2017R1A5A2015391 and 2020M3E5D9079764)(to KS).
文摘Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s lifespan.The astrocytic regulation of neuronal activity has been increasingly recognized in recent years.Astrocytes are now recognized as playing a more complex role than mere bystanders in the central nervous system.However,their role in regulating the sleep neurocircuitry is not well understood.From this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the hypothalamus.We briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.
基金supported by the National Major Science and Technology Program of China(2016YFC1306700)the National Natural Science Foundation of China(81420108012,81671046,81425010 and 31630031)+1 种基金the Jiangsu Provincial Medical Program for Distinguished Scholars(2016006)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_0167),China
文摘A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates.Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD,but its exact role in spatial memory is not well understood.The pathway arising from the postrhinal cortex(POR)and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway,the function of the pathway in spatialmemory is relatively unknown.To further illuminate the function of the UF in spatial memory,we dissected the POR–vlOFC pathway in mice.We determined that the POR–vlOFC pathway is a glutamatergic structure,and that glutamatergic neurons in the POR regulate spatial memory retrieval.We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval.These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory,as in MCI and AD.
基金the National Natural Science Foundation of China, No. 30670677
文摘BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus （TMn）, with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE： To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING： Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS： Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups（n = 5）： control, ventrolateral preoptic area （VLPO） lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma （St. Louis, USA）. METHODS： Four electroencephalogram screw electrodes were implanted into the skull at a frontal region （two） and parietal bones （two） on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette （10–20 mm tip diameter） containing ibotenic acid solution （10 nmol/L） was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline （10 nmol/L）, a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES： Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit （Micro1 401 mk2） and Data collection software （Spike Ⅱ）. RESULTS： VLPO lesion induced an increased duration of wakefulness （W, 13.17%） and light slow-wave sleep （SWS1, 28.9%）, respectively. Deep slow-wave sleep （SWS2, 43.74%） and paradoxical sleep （PS, 44.07%） were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion （P 〈 0.01）. Microinjection of bicuculline into the TMn following VLPO lesion at 10：00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% （P 〈 0.01） and 50.97% （P 〈 0.01）, respectively. In addition, SWS2 and PS were decreased by 68.08% （P 〈 0.01） and 39.92% （P 〈 0.05）, respectively, compared with prior to VLPO lesion. CONCLUSION： The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive （sleepiness） via local circuit to directly inhibit histaminergic neurons.
文摘Objective: To study the characteristics of the postsynaptic potentials in thoracic sympatheticpreganglionic neurons (SPNs) evoked by electrical stimulation of the rostral ventrolateral medulla (RVLM ) incats. Methods: In 11 α--chloralose/urethane anesthetized, artificially ventilated cats, intracellular recordings weremade from T, spinal cord with microelectrodes filled with 3 mol/L KCl. SPNs were identified by antidromicstimulation of the T3 white ramus. Results: Twenty--four SPNs were recorded, the resting membrane potentials ofwhich ranged between -- 45 -- -- 90 mV. The onset latency and threshold of the antidromic action potentialsaveraged (6. 48 + 0. 89) ms and (2. 86 + 0. 37) V respectively. Single pulse (0. 2 ms. 50-- 300 PA) electricalstimulation of RVLM evoked fast excitatory postsynaptic potentials (eEPSPs) with short latencies (4--47 ms) inall the 24 SPNs. In 11 of the SPNs, EPSPs with longer latencies (IEPSPs, 70-- 140 ms) were also recorded. Mostof the eEPSPs and some of the IEPSPs were typical monosynaptic EPSPs as they were of constant onset latency.Conclusion: The results provided direct physiological evidence for that some RVLM sympathoexcitatory neuronsproject monosynaptically to thoracic SPNs. The descending pathways from RVLM may consist of two distinctgroups of fibers, the conduction velocities were calculated to be 5--25 m/s and 0. 78-- 1. 6 m/s respectively.
基金The study was supported by grants from National Natural Science Foundation of China （No. 30370473 and No. 30770746）. We would like to thank Drs. HU Yong-sheng, ZHU Hong-wei, TAO Wei, YU Tao, MA Kai, YAN Xiao-ming, ZHANG Xiao-hua and CAI Li-xin who provide assistance to the study.
文摘Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson＇s disease （PD） and ET. Methods Thirty-six patients （PD： 20, ET： 16） were studied. Microelectrode recordings in the ventral oral posterior （Vop）and the ventral intermediate nucleus （Vim） of thalamus was performed on these patients who underwent thalamotomy.Electromyography （EMG） was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals （ISIs） were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis （K-W） test were used to compare the mean spontaneous firing rate （MSFR） of neurons of PD and ET patients. Results Three hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 （46.7%） tremor related neuronal activity, 74 neurons （22.9%） with tonic firing, and 98 （30.4%） neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 （24.6%） tremor-related neuronal activity, 77 （41.2%） neurons with tonic firing, and 64 neurons （34.2%） with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 （3.4-68.3） Hz （n=74） and that of neurons with irregular discharge （n=98） was 13.9 （3.0-58.1） Hz in PD; whereas MSFR of neurons with tonic firing （n=77） was 48.8 （19.0-135.5） Hz and that of neurons with irregular discharge （n=64） was 26.3 （8.7-84.7） Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET （K-W test, both P〈0.05）. Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET （16.3 Hz vs. 34.8 Hz, 28.0 Hz vs. 49.9 Hz） （K-W test, both P 〈0.05）, respectively. Conclusion In consistent with recent findings, the decreased MSFR of neurons observed in the Vop is likely to be involved in PD whereas the increased MSFR of neurons seen in the Vim may be a cause of ET.
基金Supported by the National Nature Science Foundation(30340071)
文摘Objective：To investigate the mechanism of the reversal effect of acupuncture on the fall of blood pressure induced by angiotensin （1-7）[Ang-（1 7）] in the caudal ventrolateral medulla （CVLM） of rats. Methods： Ang-（1-7） and its selective receptor antagonist （DAla7）, Ang（1-7） and Ang（779） were microinjected into the CVLM respectively to induce the change of blood pressure, during which, the concentrations of amino acid neurotransmitters were detected by means of microdialysis and high performance liquid chromatography （HPLC）combined with fluorescent detector, on the other hand, the effects of electro-acupuncture （EA） on the level of blood pressure and the concentrations of amino acid neurotransmitters were also observed. Results： Unilateral microinjection of Ang（1 7） into the CVLM could decrease the blood pressure （BP）, which was accompanied by an increase in the release of Glu and a decrease in the release of Tau in the same site; Whereas microinjection of Ang-779 into the CVLM could elevate BP, which was accompanied by a decrease in the release of Glu and an increase in the release of Tau; EA at acupoint Zusanli （ST 36） for 20 min could inhibit the fall of blood pressure induced by microinjection of Ang-（1-7） into the CVLM and the elevation of blood pressure induced by microinjection of Ang-779 into the CVLM, and in the meantime, it could inhibit the changes of the release of Glu and Tau induced by microinjection of Ang-（1-7） and Ang-779 into the CVLM. Conclusion： The reversal effect of EA on the fall or elevation of blood pressure induced by microinjection of Ang-（1-7） or Ang-779 into the CVLM might be related to the changes of Glu and Tau release.
基金Supported by National Natural Science Foundation of China:8197375,82074536,82104999Cultivation of Outstanding and Top Talents in Universities of Anhui Province:gxgwfx2019025Nature Science Research Project of Anhui province:2108085Y30,2108085QH36。
文摘ObjectiveTo observe the effects of pretreatment with electroacupuncture (EA) on neuron activity in the rostral ventrolateral medulla (RVLM) of rats with myocardial ischemia-reperfusion injury (MIRI) and explore the central regulatory mechanism of EA in attenuating MIRI.MethodsOf 72 SD rats, 12 were randomly allocated into the group of EA pretreatment + RVLM nucleus damage (EA + RVLM lesion group). The other 60 rats were randomized (20 rats each) into a sham-operation group, a model group, and an EA pretreatment group (EA group). Except for the rats in the sham-operation group, the models of MIRI were prepared by ligating the left anterior descending coronary artery in the model, EA, and EA + RVLM lesion groups. The rats of the EA group were intervened with EA at “Shénmén (神门HT7)” and “Tōnglĭ (通里HT5)”, 1 mA in current intensity and 2 Hz in frequency, for 20 min each time per day. Before modeling, the intervention was given for seven consecutive days. In the EA + RVLM lesion group, 3 weeks after microinjection with the neuronal apoptotic virus at bilateral RVLM, the same EA intervention as the EA group was provided. Afterward, the MIRI models were prepared. In the model group, no EA intervention was given. Using Powerlab electrophysiolograph, ST segment displacement value and arrhythmia score were recorded and analyzed before modeling, 30 min after ligation, and 120 min after reperfusion in each group. The concentration of cardiac troponin (cTnl) was detected with an ELISA assay kit. Using immunofluorescence staining, the expression level of c-fos protein of RVLM was detected in the sham-operation, model, and EA groups separately. Plexon multichannel acquisition processor was adopted to record the neuronal firing and field potential of RVLM in the sham-operation, model, and EA groups.ResultsST segment displacement value, arrhythmia score, and cTnl concentration 30 min after ligation and 120 min after reperfusion were all elevated in the model group compared to the sham-operation group (all P < 0.01). ST segment displacement value, arrhythmia score, and cTnl concentration were lower in the EA group compared to the model and EA + RVLM lesion groups (P < 0.01). Compared with the sham-operation group, the expression level of c-fos and the total firing frequency in RVLM were significantly higher in the model group (P < 0.01). However, the expression level of c-fos and the total firing frequency in RVLM were lower in the EA group compared with the model group (P < 0.01).ConclusionElectroacupuncture pretreatment may induce changes in c-fos protein expression and neuronal activity in RVLM to mitigate myocardial lesions. RVLM plays an important role in electroacupuncture pretreatment for alleviating MIRI.
基金This work was supported by grants from the National Natural Science Foundation of China(81625006,31970923,and 31820103005)the China Postdoctoral Science Foundation(2019M662025).
文摘The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors.Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei,macroscopic investigation of the characteristics of these projections,such as the spatial distribution of recipient zones,is lacking.Here,we studied the output of the cerebellar interposed nucleus(IpN)to the ventrolateral(VL)and centrolateral(CL)thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing.We found that IpN stimulation induced mono-synaptic evoked potentials(EPs)in the VL but not the CL region.Furthermore,both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space.These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.
基金supported by the Natural Science Foundation of China(31971050)the Natural Science Foundation of Hebei Province for Distinguished Young Scholars(H2020206509)+1 种基金Hebei Province Innovative Research Project for Postgraduate(2021074)the Natural Science Foundation of Hebei Province for Innovative Research Group Project(H2021206203).
文摘The nucleus tractus solitarii(NTS)is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity.Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure(BP).Here,we investigated whether phenylethanolamine N-methyltransferase(PNMT)-expressing NTS(NTS^(PNMT))neurons contribute to the control of BP.We demonstrate that photostimulation of NTS^(PNMT)neurons has variable effects on BP.A depressor response was produced during optogenetic stimulation of NTS^(PNMT)neurons projecting to the paraventricular nucleus of the hypothalamus,lateral parabrachial nucleus,and caudal ventrolateral medulla.Conversely,photostimulation of NTS^(PNMT)neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia.In addition,genetic ablation of both NTS^(PNMT)neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex.Overall,we revealed the neuronal phenotype-and circuit-specific mechanisms underlying the contribution of NTS^(PNMT)neurons to the regulation of BP.
文摘The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the known that one of the mechanisms by which angiotensin II exerts cardiovascular reflexes within the brainstem. It is well- its effect is via the activation of pathways that generate reactive oxygen species （ROS）. In the central nervous system, ROS are reported to be involved in several pathological dis- eases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.
文摘Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY) of 1-]2 weeks old and of both sexes. The systolic pressure (SP), in rats of 4-12 weeks old,increased with age and was signifficantly higher in SHR than WKY. In SHR, the increase was also significantly greater in male than female. The ir-Ang Ⅱ increased with age in all cardiovascular brain areas up to 12 weeks old in SHR, but only up to 4 weeks old in WKY. There was also sex difference in SHR. The changes in ir-Ang Ⅱ, particularly in the ventrolateral medulla (VLM), correlated well with changes in SP. The findings suggest thal interaction between brain Ang Ⅱ and cardiovascular brain areas, particularly the VLM and hypothalamus, may be crucial in the development of hypertension. The results also indicale sexual dimorphism in brain Ang Ⅱ in addition to blood pressure reaction in the developing SHR.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(No.81371256,81171061,81361128012)Ministry of Education of Republic of China(BIBD-PXM2013-014226-07-000084)Seed Grant of International Alliance of Translational Neuroscience(PXM2014-014226-000015).
文摘Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion.While both basal ganglia and thalamus have tremor activity,the thalamus appears to play a more important role in tremor production,and basal ganglia β oscillatory activity might be the trigger.
