Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin

The hippocampus receives a dense serotonin-containing innervation from the divisions of the raphe nucleus. Serotonin applied to hippocampal neurons to mimic the action of endogenous transmitter often produces complex and variable responses (see for example ref. 3). Using voltage-clamp methods and new ligands that are selective for subtypes of serotonin receptors, we have been able to clarify the mechanism of serotonin action on CA1 cells in rat hippocampal slices. We describe three distinct actions of serotonin (or 5-HT) on identified K-conductances in these cells. First, it activates a Ca-independent K-current which is responsible for neuronal hyperpolarization and is inhibitory. Second, it simultaneously suppresses the slow Ca-dependent K-conductance that is largely responsible for the accommodation of cell firing in CA1 neurons: this produces a paradoxical increase in neuronal discharge in response to a depolarizing input. Third, serotonin produces a more slowly developing and long-lasting suppression of an intrinsic voltage-dependent K-conductance, Im (ref. 9), leading to neuronal depolarization and excitation. The hyperpolarizing response is mediated by class 1A serotonin receptors, whereas the other responses are not. Modulation of these different conductances by endogenously released serotonin could therefore change the probability or the duration (or both) of neuronal firing in the mammalian brain in different ways to give inhibitory, excitatory or mixed effects.     

Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CA1 pyramidal cell dendrites

In the CA1 hippocampal region, intracellular calcium is a putative second messenger for the induction of long-term potentiation (LTP), a persistent increase of synaptic transmission produced by high frequency afferent fibre stimulation. Because LTP in this region is blocked by the NMDA (N-methyl-D-aspartate) receptor antagonist AP5 (DL-2-amino-5-phosphonovaleric acid) and the calcium permeability of NMDA receptors is controlled by a voltage-dependent magnesium block, a model has emerged that suggests that the calcium permeability of NMDA receptor-coupled ion channels is the biophysical basis for LTP induction. We have performed microfluorometric measurements in individual CA1 pyramidal cells during stimulus trains that induce LTP. In addition to a widespread component of postsynaptic calcium accumulation previously described, we now report that brief high frequency stimulus trains produce a transient component spatially localized to dendritic areas near activated afferents. This localized component is blocked by the NMDA receptor antagonist AP5. The results directly confirm the calcium rise predicted by NMDA receptor models of LTP induction.     

脑室注射海人酸对大白鼠学习记忆行为的影响

大白鼠脑室注射海人酸(KA)5天后,检查被动回避行为和脑组织学变化。发现受注射一侧海马的背側CA3a分区锥体细胞破坏,对长时记忆,特别是长时记忆形成能力有严重损害,对学习和短时记忆无明显影响。增大KA剂量,对锥体细胞的破坏范围也扩大,能波及CA3,CA4和CAl区锥体细胞,双侧注射KA,两侧海马的背侧锥体细胞都有损毁,但对学习记忆行为的损害程度并不增高。这些结果提示,海马背侧CA3a分区锥体细胞在被动回避反应行为的长时记忆形成中有重要意义;长时记忆与学习和短时记忆的形成,在海马结构中可能有不同的神经基础,脑室注射KA后2月,海马锥体细胞的破坏仍未见恢复,长时记忆形成能力的受损亦未能代偿。本文还讨论了海马CA3影响长时记忆过程的可能神经机理。     

虫草素改善脑缺血小鼠学习记忆及保护海马神经元的作用研究

采用双侧颈动脉夹闭建立脑缺血模型,分别观察造模后和造模前腹腔注射100 mg?kg-1虫草素对小鼠Y迷宫行为训练的影响以及检测海马各区神经元数量的变化.结果表明,造模前给予虫草素能明显提高小鼠的正确反应率（p0.05）,减少达标所需训练次数（p0.05）,并显著增加海马CA1区和CA3区锥体神经元数量（p0.01）.造模后给予虫草素对小鼠的正确反应率没有显著影响（p0.05）,但显著减少达标所需训练次数（p0.05）;同时,海马CA3区神经元数量显著增加（p0.01）,而CA1区没有显著变化（p0.05）.由此可见,虫草素能改善脑缺血小鼠的学习能力,预防作用似乎比治疗作用更为显著,其相关机制可能与虫草素促进海马神经元的修复有关.     

Latent synaptic pathways revealed after tetanic stimulation in the hippocampus

Synaptic plasticity may result from changes at existing synapses or from alterations in the number of functional synaptic connections. In the hippocampus excitatory synaptic strength is persistently enhanced after tetanic stimulation. Here we report that latent synaptic pathways may also become functional. Simultaneous intracellular recordings were made from pairs of CA3 pyramidal cells in slices from guinea pig hippocampus. After stimulating afferent fibres repetitively, polysynaptic excitatory pathways between previously unconnected cells became apparent. The efficacy of recurrent inhibitory circuits was also reduced. The loss of inhibitory control is of interest because latent excitatory pathways are revealed after pharmacological suppression of inhibition. This plasticity in local synaptic circuits leads to the emergence of synchronous firing in groups of CA3 cells. The formation of groups of associated cells and the ability of some cells to initiate synchronous firing in a larger cell group through recurrent pathways is reminiscent of several models of information storage and recall in the cortex.     

脑震荡后综合征大鼠海马的神经损伤及磁共振波谱分析

目的:探讨脑震荡损伤对大鼠海马区代谢物水平的影响及其病理机制.方法:将25只成年雄性SD大鼠随机分为对照组(n=10)和PCS组(n=15),采用Marmarou改良法复制大鼠脑震荡损伤模型,对脑震荡24h大鼠及对照组大鼠进行1H-MRS扫描后处死,对脑组织进行免疫组织化学和免疫荧光染色观察海马CA1区的残存锥体细胞和凋亡细胞的数量.结果:1H-MRS扫描结果显示,PCS组大鼠左侧海马区NAA/Cr水平(0.824±0.17)明显低于正常对照组(1.299±0.12),P<0.01;PCS组大鼠右侧海马NAA/Cr水平(0.792±0.17)明显低于正常对照组(1.287±0.18),P<0.01.PCS组大鼠海马CA1区小血管扩张淤血,锥体细胞呈代偿肥大与凋亡并存状态.免疫组织化学结果显示,PCS组大鼠海马CA1区NeuN阳性细胞数量(176.17±26.92)较正常对照组(228.33±26.34)明显减少,P<0.05;免疫荧光实验结果显示,PCS组海马CA1区凋亡细胞的数量(48.03±5.46)较正常对照组(35.49±7.75)明显增多,P<0.01.结论:脑震荡后大鼠双侧海马区神经细胞的代谢物水平均下降,海马CA1区残存锥体细胞数量减少和凋亡细胞增多,后者可能是代谢物水平变化的病理基础.     

Cellular networks underlying human spatial navigation

Place cells of the rodent hippocampus constitute one of the most striking examples of a correlation between neuronal activity and complex behaviour in mammals. These cells increase their firing rates when the animal traverses specific regions of its surroundings, providing a context-dependent map of the environment. Neuroimaging studies implicate the hippocampus and the parahippocampal region in human navigation. However, these regions also respond selectively to visual stimuli. It thus remains unclear whether rodent place coding has a homologue in humans or whether human navigation is driven by a different, visually based neural mechanism. We directly recorded from 317 neurons in the human medial temporal and frontal lobes while subjects explored and navigated a virtual town. Here we present evidence for a neural code of human spatial navigation based on cells that respond at specific spatial locations and cells that respond to views of landmarks. The former are present primarily in the hippocampus, and the latter in the parahippocampal region. Cells throughout the frontal and temporal lobes responded to the subjects' navigational goals and to conjunctions of place, goal and view.     

Non-classical receptive field mediates switch in a sensory neuron's frequency tuning

Animals have developed stereotyped communication calls to which specific sensory neurons are well tuned. These communication calls must be discriminated from environmental signals such as those produced by prey. Sensory systems might have evolved neural circuitry to encode both categories. In weakly electric fish, prey and communication signals differ in their spatial extent and frequency content. Here we show that stimuli of different spatial extents mimicking prey and communication signals cause a switch in the frequency tuning and spike-timing precision of electrosensory pyramidal neurons, resulting in the selective and optimal encoding of both stimulus categories. As in other sensory systems, pyramidal neurons respond only to stimuli located within a restricted region of space known as the classical receptive field (CRF). In some systems, stimulation outside the CRF but within a non-classical receptive field (nCRF) can modulate the neural response to CRF stimulation even though nCRF stimulation alone fails to elicit responses. We show that pyramidal neurons possess a nCRF and that it can modulate the response to CRF stimuli to induce this neurobiological switch in frequency tuning.     

Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons

The hippocampus is necessary for the acquisition and retrieval of declarative memories. The best-characterized sensory input to the hippocampus is the perforant path projection from layer II of entorhinal cortex (EC) to the dentate gyrus. Signals are then processed sequentially in the hippocampal CA fields before returning to the cortex via CA1 pyramidal neuron spikes. There is another EC input-the temporoammonic (TA) pathway-consisting of axons from layer III EC neurons that make synaptic contacts on the distal dendrites of CA1 neurons. Here we show that this pathway modulates both the plasticity and the output of the rat hippocampal formation. Bursts of TA activity can, depending on their timing, either increase or decrease the probability of Schaffer-collateral (SC)-evoked CA1 spikes. TA bursts can also significantly reduce the magnitude of synaptic potentiation at SC-CA1 synapses. The TA-CA1 synapse itself exhibits both long-term depression (LTD) and long-term potentiation (LTP). This capacity for bi-directional plasticity can, in turn, regulate the TA modulation of CA1 activity: LTP or LTD of the TA pathway either enhances or diminishes the gating of CA1 spikes and plasticity inhibition, respectively.     

Effects of carnosine on the evoked potentials in hippocampal CA1 region

Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine transformed population spikes (PSs) with single spike into epileptiform multiple spikes. In addition, similar to the effect of γ-aminobutyric acid_A (GABA_A) antagonist picrotoxin, carnosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion: The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.     

Inhibitory feedback required for network oscillatory responses to communication but not prey stimuli

Stimulus-induced oscillations occur in visual, olfactory and somatosensory systems. Several experimental and theoretical studies have shown how such oscillations can be generated by inhibitory connections between neurons. But the effects of realistic spatiotemporal sensory input on oscillatory network dynamics and the overall functional roles of such oscillations in sensory processing are poorly understood. Weakly electric fish must detect electric field modulations produced by both prey (spatially localized) and communication (spatially diffuse) signals. Here we show, through in vivo recordings, that sensory pyramidal neurons in these animals produce an oscillatory response to communication-like stimuli, but not to prey-like stimuli. On the basis of well-characterized circuitry, we construct a network model of pyramidal neurons that predicts that diffuse delayed inhibitory feedback is required to achieve oscillatory behaviour only in response to communication-like stimuli. This prediction is experimentally verified by reversible blockade of feedback inhibition that removes oscillatory behaviour in the presence of communication-like stimuli. Our results show that a sensory system can use inhibitory feedback as a mechanism to 'toggle' between oscillatory and non-oscillatory firing states, each associated with a naturalistic stimulus.     

A network of fast-spiking cells in the neocortex connected by electrical synapses

Encoding of information in the cortex is thought to depend on synchronous firing of cortical neurons. Inhibitory neurons are known to be critical in the coordination of cortical activity, but how interaction among inhibitory cells promotes synchrony is not well understood. To address this issue directly, we have recorded simultaneously from pairs of fast-spiking (FS) cells, a type of gamma-aminobutyric acid (GABA)-containing neocortical interneuron. Here we report a high occurrence of electrical coupling among FS cells. Electrical synapses were not found among pyramidal neurons or between FS cells and other cortical cells. Some FS cells were interconnected by both electrical and GABAergic synapses. We show that communication through electrical synapses allows excitatory signalling among inhibitory cells and promotes their synchronous spiking. These results indicate that electrical synapses establish a network of fast-spiking cells in the neocortex which may play a key role in coordinating cortical activity.     

Transitional function of DG to CA3 in the hippocampus

Using single cell channel model, the transmission features of CA3-DG network in the hippocampus are investigated. The influence of the stimulation on discharge pattern of pyramidal neurons is analyzed, which shows that it starts with period spiking discharges, followed by period-doubling bifurcation to chaos, and period 3 discharge evolving into chaos, and ultimately a period of bursting discharges. By the synaptic model, the CA3-DG network model is constructed, which analyzes the summation of postsynaptic currents in the network, the influence of postsynaptic current on discharge rhythm as well as the mechanism of bursting discharges. The strong capacity of spatiotemporal encoding in the network indicates the features of CA3 network during the information transmission process in the hippocampus. The modeling result with time delay of the synaptic transmission is in accordance with the experimental phenomena of action potential in the hippocampus.     

Transitional function of DG to CA3 in the hippocampus

Using single cell channel model, the transmission features of CA3-DG network in the hippocampus are investigated. The influence of the stimulation on discharge pattern of pyramidal neurons is analyzed, which shows that it starts with period spiking discharges, followed by period-doubling bifurcation to chaos, and period 3 discharge evolving into chaos, and ultimately a period of bursting discharges. By the synaptic model, the CA3-DG network model is constructed, which analyzes the summation of postsynaptic currents in the network, the influence of postsynaptic current on discharge rhythm as well as the mechanism of bursting discharges. The strong capacity of spatiotemporal encoding in the network indicates the features of CA3 network during the information transmission process in the hippocampus. The modeling result with time delay of the synaptic transmission is in accordance with the experimental phenomena of action potential in the hippocampus.     

Routing of spike series by dynamic circuits in the hippocampus

Recurrent inhibitory loops are simple neuronal circuits found in the central nervous system, yet little is known about the physiological rules governing their activity. Here we use simultaneous somatic and dendritic recordings in rat hippocampal slices to show that during a series of action potentials in pyramidal cells recurrent inhibition rapidly shifts from their soma to the apical dendrites. Two distinct inhibitory circuits are sequentially recruited to produce this shift: one, time-locked with submillisecond precision to the onset of the action potential series, transiently inhibits the somatic and perisomatic regions of pyramidal cells; the other, activated in proportion to the rate of action potentials in the series, durably inhibits the distal apical dendrites. These two operating modes result from the synergy between pre- and postsynaptic properties of excitatory synapses onto recurrent inhibitory neurons with distinct projection patterns. Thus, the onset of a series of action potentials and the rate of action potentials in the series are selectively captured and transformed into different spatial patterns of recurrent inhibition.     

Slow transmission of neural activity in hippocampal area CA1 in absence of active chemical synapses

Transmission of neural activity in the mammalian cortex involves the operation of chemical synapses. Here we report that activity of hippocampal pyramidal cells (HPC) in vitro can spread through the neural aggregate even when chemical synaptic transmission is blocked by lowering the external Ca2+ concentration ( [Ca2+]0). In these conditions focal stimulation of the HPC body layer (stratum pyramidale) at area CA1 evokes a localized repetitive neural response which, when large enough, spreads along this layer in both transverse directions. It was recently reported for similar conditions that the activated HPC often discharge in synchrony. However, the spread of the neural response does not depend upon the occurrence of synchronized HPC activity, and therefore represents a distinct phenomenon.     

Independent rate and temporal coding in hippocampal pyramidal cells

In the brain, hippocampal pyramidal cells use temporal as well as rate coding to signal spatial aspects of the animal's environment or behaviour. The temporal code takes the form of a phase relationship to the concurrent cycle of the hippocampal electroencephalogram theta rhythm. These two codes could each represent a different variable. However, this requires the rate and phase to vary independently, in contrast to recent suggestions that they are tightly coupled, both reflecting the amplitude of the cell's input. Here we show that the time of firing and firing rate are dissociable, and can represent two independent variables: respectively the animal's location within the place field, and its speed of movement through the field. Independent encoding of location together with actions and stimuli occurring there may help to explain the dual roles of the hippocampus in spatial and episodic memory, or may indicate a more general role of the hippocampus in relational/declarative memory.     

Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo

Neural-network oscillations at distinct frequencies have been implicated in the encoding, consolidation and retrieval of information in the hippocampus. Some GABA (gamma-aminobutyric acid)-containing interneurons fire phase-locked to theta oscillations (4-8 Hz) or to sharp-wave-associated ripple oscillations (120-200 Hz), which represent different behavioural states. Interneurons also entrain pyramidal cells in vitro. The large diversity of interneurons poses the question of whether they have specific roles in shaping distinct network activities in vivo. Here we report that three distinct interneuron types--basket, axo-axonic and oriens-lacunosum-moleculare cells--visualized and defined by synaptic connectivity as well as by neurochemical markers, contribute differentially to theta and ripple oscillations in anaesthetized rats. The firing patterns of individual cells of the same class are remarkably stereotyped and provide unique signatures for each class. We conclude that the diversity of interneurons, innervating distinct domains of pyramidal cells, emerged to coordinate the activity of pyramidal cells in a temporally distinct and brain-state-dependent manner.     

论CA数字证书与组织机构代码证书的协同应用

CA数字证书是电子政务和电子商务的基础工具，组织机构代码是国家管理现代化的重要工具，二的协同应用可以互相促进，并最大限度发挥二的作用，应用的主要方法是在组织机构代码证书IC卡中植入CA数字证书。为此，还必须解决一系列法律、制度与政策等问题。