In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cyt...In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.展开更多
Chronic experiments with rabbits have shown that electrical destruction of dorsal amygdalofugal pathways leads to complete and persisted blockade of hippocampal theta rhythm in contrast to ventral one. In intact anima...Chronic experiments with rabbits have shown that electrical destruction of dorsal amygdalofugal pathways leads to complete and persisted blockade of hippocampal theta rhythm in contrast to ventral one. In intact animals, electro- and chemostimulation of amygdala nuclei, hypothalamus, reticular formation and medial septum nucleus lead to the formation of well pronounced theta rhythm in hippocampus, but after destruction of the amygdalofugal pathway any theta-rhythm in this structure is not observed. Restoration of hippocampal EEG took place under intrahippocampal application of carbocholine and strychnine. It is proposed that one of the necessary conditions for the regulation of excitability of hippocampal neurons is the integrity of dorsal amygdalofugal pathways by means of which regulatory influence of amygdale on the hippotalamic neurosecretory cells is realized.展开更多
Recently it was shown by us that combined stimulation of hippocampus and dorsomedial hypothalamus resulted in suppression of the electroencephalographic seizure reactions and, respectively, manifestations of behaviora...Recently it was shown by us that combined stimulation of hippocampus and dorsomedial hypothalamus resulted in suppression of the electroencephalographic seizure reactions and, respectively, manifestations of behavioral seizures reduced. It is expected, that augmentation of inhibitory processes in hippocampal neurons in the course of dorsomedial hypothalamus stimulation can trigger mechanisms preventing the development of epileptiform activity. Because of two important characteristics of the hippocampus—theta rhythm and epileptogenesis—these appear to be interrelated in respect of their cellular substrates, and as far as theta rhythm may modulate hippocampal excitability, a study of the functional relationship between theta rhythm and seizure activity was endeavored. The purpose of this study is to test this proposal by determining the effects on seizures of induction or suppression of hippocampal theta activity. Our findings show that: 1) against background of strong unusual sound stimulation (in our case-sound) blockade of local seizure reactions induced by hippocampal stimulation occurred;2) the frequency of hippocampal interictal epileptiform dischargers increased with the transition from the awake state to drowsiness and a slow-wave sleep phase. After the animal came from slow-wave sleep to paradoxical sleep, epileptiform activity completely disappeared;3) at threshold stimulation of hypothalamus when electrohippocampogram shows augmentation of the theta rhythm there is a significant reduction of seizure durations. When at hypothalamus stimulation instead of theta rhythm the electrical activity is desynchronized, there occurs a considerable intensification of seizure activity. Therefore, seizure-theta antagonism in our experiments could be interpreted as an adjustment of the inhibitory mechanisms when the theta rhythm is evoked.展开更多
Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural acti...Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural activities in the frontal eye field(FEF)and V4 simultaneously when monkeys performed a free-gaze visual search task.Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials,and the phase-locking was dependent on saccade direction.The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response.V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases.Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing.Together,our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas,in addition to the theta phase locking caused by saccade-triggered responses.展开更多
基金supported by the National Natural Science Foundation of China,No.31600865(to ZJW)“Sanjin Scholars”of Shanxi Province of China,No.[2016]7(to MNW)+5 种基金Shanxi Province Science Foundation for Excellent Young Scholars of China,No.201801D211005(to MNW)the Applied Basic Research Program of Shanxi Province of China,No.201901D111358(to GZY)the Doctoral Startup Research Fund of Shanxi Medical University of China,No.03201536(to GZY)the Doctoral Startup Research Fund of the First Hospital of Shanxi Medical University of China,No.YJ1507(to GZY)the National Undergraduate Innovation Program of China,No.201910114019(to JXW)the Undergraduate Innovation Program of Shanxi Province of China,No.2020189(to XRZ).
文摘In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.
文摘Chronic experiments with rabbits have shown that electrical destruction of dorsal amygdalofugal pathways leads to complete and persisted blockade of hippocampal theta rhythm in contrast to ventral one. In intact animals, electro- and chemostimulation of amygdala nuclei, hypothalamus, reticular formation and medial septum nucleus lead to the formation of well pronounced theta rhythm in hippocampus, but after destruction of the amygdalofugal pathway any theta-rhythm in this structure is not observed. Restoration of hippocampal EEG took place under intrahippocampal application of carbocholine and strychnine. It is proposed that one of the necessary conditions for the regulation of excitability of hippocampal neurons is the integrity of dorsal amygdalofugal pathways by means of which regulatory influence of amygdale on the hippotalamic neurosecretory cells is realized.
文摘Recently it was shown by us that combined stimulation of hippocampus and dorsomedial hypothalamus resulted in suppression of the electroencephalographic seizure reactions and, respectively, manifestations of behavioral seizures reduced. It is expected, that augmentation of inhibitory processes in hippocampal neurons in the course of dorsomedial hypothalamus stimulation can trigger mechanisms preventing the development of epileptiform activity. Because of two important characteristics of the hippocampus—theta rhythm and epileptogenesis—these appear to be interrelated in respect of their cellular substrates, and as far as theta rhythm may modulate hippocampal excitability, a study of the functional relationship between theta rhythm and seizure activity was endeavored. The purpose of this study is to test this proposal by determining the effects on seizures of induction or suppression of hippocampal theta activity. Our findings show that: 1) against background of strong unusual sound stimulation (in our case-sound) blockade of local seizure reactions induced by hippocampal stimulation occurred;2) the frequency of hippocampal interictal epileptiform dischargers increased with the transition from the awake state to drowsiness and a slow-wave sleep phase. After the animal came from slow-wave sleep to paradoxical sleep, epileptiform activity completely disappeared;3) at threshold stimulation of hypothalamus when electrohippocampogram shows augmentation of the theta rhythm there is a significant reduction of seizure durations. When at hypothalamus stimulation instead of theta rhythm the electrical activity is desynchronized, there occurs a considerable intensification of seizure activity. Therefore, seizure-theta antagonism in our experiments could be interpreted as an adjustment of the inhibitory mechanisms when the theta rhythm is evoked.
基金We are grateful for the financial support from the National Natural Science Foundation of China(31671108 and 31800900)the National Key R&D Program of China(2017YFC1307500)+1 种基金the Shenzhen Science and Technology Innovation Commission(JCYJ20180508152240368)the Shenzhen Basic Research Program(JCYJ20200109114805984).
文摘Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural activities in the frontal eye field(FEF)and V4 simultaneously when monkeys performed a free-gaze visual search task.Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials,and the phase-locking was dependent on saccade direction.The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response.V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases.Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing.Together,our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas,in addition to the theta phase locking caused by saccade-triggered responses.
