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Dual face of axonal inhibitory inputs in the modulation of neuronal excitability in cortical pyramidal neurons

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Neural Regeneration Research 2017年第7期12卷 1079-1085页

作者： Lei Jiang Hong Ni Qi-yi Wang Li Huang Shi-di Zhao Jian-dong Yu Rong-jing Ge Department of Pathophysiology Bengbu Medical College Bengbu Anhui Province China Department of General Surgery The Second Affiliated Hospital of Bengbu Medical College Bengbu Anhui Province China Department of Physiology Bengbu Medical College Bengbu Anhui Province China Guangdong-Hongkong-Macao Institute of CNS Regeneration Joint International Research Laboratory of CNS Regeneration Ministry of Education Jinan University Guangzhou Guangdong Province China

Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.

关键词： nerve regeneration cortex pyramidal neuron soma axon hyperpolarization neuronal network feedforward inhibition temporalintegration feedback inhibition excitability neural regeneration

Subjective tinnitus: lesion-induced pathological central homeostasis remodeling

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Journal of Otology 2021年第4期16卷 266-272页

作者： Qi Zhang Lidong Zhao Weidong Shen Shiming Yang Department of Otolaryngology Head and Neck SurgeryInstitute of OtolaryngologyChinese PLA General HospitalFuxing Street NO.28Haidian DistrictBeijing100039China

Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affectspatients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatmentof subjective tinnitus remains challenging. In recent decades, a growing number of studies have shownthat subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory centralsystems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to providefurther understanding of its pathogenesis.

关键词： Tinnitus Neural plasticity Homeostasis Interneuron GABA pyramidal neuron

FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus

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Neuroscience Bulletin 2021年第3期37卷 298-310页

作者： Yang Ni Bin Liu Xiaojing Wu Junhua Liu Ru Ba Chunjie Zhao Key Laboratory of Developmental Genes and Human Diseases Ministry of EducationSchool of MedicineSoutheast UniversityNanjing 210009China

The Wnt signaling pathway plays key roles in various developmental processes.Wnt5a,which activates the non-canonical pathway,has been shown to be particularly important for axon guidance and outgrowth as well as dendrite morphogenesis.However,the mechanism underlying the regulation of Wnt5a remains unclear.Here,through conditional disruption of Foxg1 in hippocampal progenitors and postmitotic neurons achieved by crossing Foxg1~(fl/fl)with Emx1-Cre and Nex-Cre,respectively,we found that Wnt5a rather than Wnt3a/Wnt2b was markedly upregulated.Overexpression of Foxg1 had the opposite effects along with decreased dendritic complexity and reduced mossy fibers in the hippocampus.We further demonstrated that FOXG1 directly repressed Wnt5a by binding to its promoter and one enhancer site.These results expand our knowledge of the interaction between Foxg1 and Wnt signaling and help elucidate the mechanisms underlying hippocampal development.

关键词： Wnt5a Foxg1 hippocampus granule cell pyramidal neuron dendritic arborization mossy fiber Wnt

Hippocampal ultrastructural changes and apoptotic cell death in rats following endurance training and acute exhaustive exercise

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Neural Regeneration Research 2008年第6期3卷 679-682页

作者： Jianjun Zhang Physical Education College Zhengzhou University Zhengzhou 450044 Henan Province China

BACKGROUND： Exhaustive exercise can lead to apoptosis of skeletal muscle cells and myocardial cells as a result of pathological changes in the corresponding cellular ultrastructure. It is hypothesized that such changes could also occur in neurons. OBJECTIVE： To observe brain cell apoptosis and ultrastructural changes in hippocampal neurons in rats following endurance training and acute exhaustive exercise. DESIGN, TIME AND SETTING： A randomized, controlled, morphological analysis was performed at the Medical Laboratory Center of Zhengzhou University between July and November 2007. MATERIALS： Forty male, 8-week-old, Sprague Dawley rats were included in this study. METHODS： Endurance training consisted of treadmill running once a day, 6 days a week, for 4. weeks. For acute exhaustive exercise, graded treadmill running was conducted. Rats were exposed to exercise at an increasing speed （10 m/min, increasing to 20 and 36 m/min for moderate- and high-intensity exhaustive exercise, respectively, and then was continued until exhaustion）. A total of 40 rats were evenly distributed into the following 4. groups： Group A rats were not exercised; Group B rats were not trained but sacrificed 24 hours after acute exhaustive treadmill running exercise; Group C-rats were subjected to endurance training and sacrificed immediately after acute exhaustive treadmill running exercise; Group D rats were subjected to endurance training and sacrificed 24 hours after acute exhaustive treadmill running exercise. MAIN OUTCOME MEASURES： Apoptotic cell death was detected by the TUNEL method and hippocampal neuronal ultrastructural change was observed through using transmission electron microscopy. RESULTS： All 40 rats were included in the final analysis. Subsequent to exhaustive exercise, rat cerebral cortex and hippocampal neurons appeared contracted and degenerated. In addition, high amount of lipofuscin was visible in the hippocampal region, Necrotic neurons encased by glial cells appeared in the cerebral cortex and hippocampus. Glial cell

关键词： endurance training exhaustive exercise apoptosis pyramidal neuron mitochondrion

Takeda G protein-coupled receptor 5 modu⁃lates depression-like behaviors via hippocam⁃pal CA3 pyramidal neurons afferent to dorso⁃lateral septum

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中国药理学与毒理学杂志 2021年第9期35卷 689-690页

作者： WANG Hao TAN Yuan-zhi MU Rong-hao TANG Su-su LIU Xiao XING Shu-yun LONG Yan YUAN Dan-hua HONG Hao Department of Pharmacology Key Laboratory of Neuropsychiatric DiseasesChina Pharmaceutical UniversityNanjing 211198China

OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.

关键词： depression dorsolateral septum GABAergic neuron hippocampus pyramidal neuron takeda G protein-coupled receptor 5

Gene expression profiling of subcortical projection neusons from different cortical area

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Gene expression profiling of subcortical projection neusons ...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Chun-Sheng QU,Jian XIAO,Lin-Hua CHEN,Jia QU,Jie-Guang CHEN~* School of Optometry and Ophthalmology,Wenzhou Medical College,Wenzhou 325027,China

＜正＞The mammalian cerebral cortex receives and integrates sensory information from the body,and sends out regulatory controlling signals by descending projection neurons in the layer V of cortex.Projection neurons from motor and sensory cortices innervate distinct subcortical brain regions.Visual cortical neurons projects to the superior colliculus, in contrast,motor neuron axons terminate in the spinal cord.The maturation of different projections is an early postnatal process due to selective axon prunning.To discover the key molecules underlying the different projection neurons,we have labeled the subcortical projection neurons in P8 mouse brain by retrograde tracing from the pyramidal decussation, and isolated the labeled neurons from visual and motor cortices separately by laser capture microdissection.After amplification,the mRNA profiles were determined by microarray screening,and compared each other as well as to that from the cortical tissues.We have identified multiple genes that are highly enriched in the subcortical projection neurons. Among them,more than 100 genes were found to be differentially expressed in the projection neurons from visual cortex compared to that from motor cortex.The expression pattern is being verified by real-time PCR and in situ hybridization.The differentially expressed genes may contribute to the developmental axon prunning,which will be tested by altering their expression in vivo.

关键词： microarray screening pyramidal neuron visual cortex retrograde tracing gene expression.

Serotoninergic modulation and contribution of sodium channel subtypes in action potential initiation and backpropagation

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Serotoninergic modulation and contribution of sodium channel...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Wen-Qin HU,Cui-Ping TIAN,Tun LI,Ming-Po YANG,Han HOU,You-Sheng SHU~* Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,200031,China

It has been long believed that the high Na channel density at the distal axon initial segment(AIS) determines the lowest threshold for action potential initiation.However,it has been unclear why action potentials are not initiated at the proximal AIS,which has a similarly high Na channel density.Our immunostaining results indicated that low-threshold Nav1.6 and high-threshold Nav1.2 channels preferentially accumulated at the distal and proximal AIS,respectively.Patchclamp recording from the axon cut end of pyramidal neurons in the rat prefrontal cortex revealed a high density of Na current and a progressive reduction(hyperpolarization) in the half-activation voltage(up to 14 mV) with increasing distance from the soma at the AIS.Further modeling studies and simultaneous somatic and axonal recordings showed that distal Nav1.6 promotes action potential initiation,whereas proximal Nav1.2 promotes its backpropagation to the soma. Interestingly,our immunostaining experiments also showed a co-localization of serotonin(5-HT) 1A receptor and Nav 1.2 at the proximal region of the AIS in pyramidal neurons.Activation of 5-HT 1A receptor significantly suppressed the AIS Na current and reduced the probability of action potential propagation to the soma.Together,these results showed that (1) Nav1.6 and Nav1.2 had distinct function in action potential initiation and backpropagation;(2) modulation of AIS Na channels by 5-HT1A receptor may gate the action potential propagation to the soma.

关键词： pyramidal neuron axon initial segment action potential Nav 1.2 Nav 1.6,5-HT 1A receptor

Membrane potential fluctuation modulates cortical recurrent inhibition

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Membrane potential fluctuation modulates cortical recurrent ...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jie ZHU~1,Yousheng SHU~(1,*) 1 Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

A balance of excitation and inhibition is critical for cortical proper functioning.Disruption of this balance may result in severe brain disorders such as schizophrenia and epilepsy.Cortical neurons are constantly bombarded by postsynaptic potentials,interaction of these potentials and neuronal intrinsic properties leads to membrane potential(V fluctuations.It is,therefore,important to understand how the balance is achieved at different V levels in accordance to various cortical activity states.Whole-cell recording from paired layer-5 PCs in rat somatosensory cortical slices revealed that both the slow and the fast disynaptic IPSPs,presumably mediated by low-threshold spiking and fast spiking interneurons respectively,were modulated by changes in presynaptic V.Somatic depolarization(larger than 5 mV) of the presynaptic PC substantially increased the amplitude and shortened the onset latency of the slow disynaptic IPSPs in neighboring PCs,leading to a narrowed time window for EPSP integration.Similar increase in the amplitude of the fast disynaptic IPSPs in response to presynaptic depolarization was also observed.Further paired recording from PCs and interneurons revealed that PC depolarization increases EPSP amplitude and thus elevates interneuronal firing and inhibition of neighboring PCs.This PC V -dependent modulation of EPSPs results from a mode of synaptic transmission known as the analog transmission between PCs and interneurons.Together,these results revealed that immediate PC V -dependent modulation of cortical inhibition is a key strategy through which the cortex efficiently and dynamically maintains the excitation-inhibition balance,a condition critical for cortical information processing.

关键词： pyramidal neuron inhibitory intemeuron recurrent inhibition disynaptic IPSPs membrane potential rat somatosensory cortex

Oscillatory coding by apical dendrite of pyramidal neurons in the prefrontal cortex

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Oscillatory coding by apical dendrite of pyramidal neurons i...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Chang-Liang LIU~1,Guo-Zhang JIN~1,Xiao-Hua CAO~2,Xue-Chu ZHEN~(1,3,*) 1 Department of Pharmacology,State Key Laboratory of Drug Research,Institute of Materia Medica,Shanghai Institute for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 2 Brain Functional Genomic Institute,ECNU,China 3 Department of Pharmacology,College of Pharmacy,Soochow University,China

Oscillatory firing is an important process in neural system for presenting,integrating and synchronizing neuronal signals.Though most pyramidal neurons are able to oscillate at a broad band,only a few specific neurons in brain can generate oscillation spontaneously.Here we report a novel oscillation elicited by glutamate applied to the apical dendrite of pyramidal neuron.We found that glutamate-elicited oscillation was dependent on activation of NMDA receptor and was evoked only in apical dendrite but not in soma.The firing is an intrinsic property of individual neuron and depends on extracellular Mg and Ca.A parallel change between intracellular Ca and oscillating membrane potential was clearly observed during oscillation,with much stronger calcium oscillation in dendrite than that in soma.Further study showed that two calcium-activated currents SK and AHP current underlie the repolarization phase of the firing.And the frequency of the oscillation is dominated by HCN channel,a channel increasingly distributed along dendrite.Dopamine was found to modulate the firing by prolonging the firing duration and increasing oscillation frequency.However,in cocaine withdrawal rats,dopamine application still produced prolonged duration but with decreased frequency.By the use of single unit recording techniques and spectral analysis, we also proved that in vivo slow oscillation shares similar mechanisms of the dendritically induced oscillation,thus indicating possible existence of the firing under physiological condition.These data demonstrate an interesting oscillatory coding mechanism in the apical dendrite and shed light on potential coding changes by addictive drugs.

关键词： apical dendrite pyramidal neuron prefrontal cortex oscillation NMDA receptor dopamine cocaine