淀粉样β蛋白抑制大鼠海马theta节律并致行为脱抑制和空间记忆损伤

海马神经元网络振荡与哺乳动物学习记忆、焦虑及行为抑制密切相关。阿尔茨海默病患者早期表现出的认知功能减退及行为脱抑制,极可能与海马内沉积的淀粉样β蛋白(amyloid β protein,Aβ)损伤了海马神经元网络电活动有关,但海马注射Aβ能否在伤害学习记忆功能的同时也引起行为脱抑制和改变神经元同步化活动,仍缺乏足够的动物实验证据。本研究利用Morris水迷宫、高架十字迷宫和在体局部场电位记录技术,观察了海马注射Aβ1–42寡聚体对大鼠空间学习记忆和行为抑制活动的影响,并分析了海马theta节律的改变。结果表明,与对照组相比,海马注射Aβ1–42寡聚体两周后:(1)大鼠在高架十字迷宫中焦虑性减低,出现明显的行为脱抑制现象,去开臂次数和在开臂停留时间均明显增加;(2)大鼠空间学习、记忆严重受损,水迷宫定位航行实验中寻找水下平台的潜伏期明显延长,空间探索实验中在原平台象限的游泳时间百分比明显减小;(3)大鼠海马CA1区theta节律压抑,由夹尾刺激诱导的theta节律的功率峰值明显减低,而theta节律功率峰值对应的频率值未发生改变。以上结果表明,海马注射Aβ1–42寡聚体可同时引起大鼠行为脱抑制、空间记忆损伤和海马theta节律压抑。这提示,AD患者出现的学习记忆能力障碍和精神行为异常很可能与Aβ对海马神经元网络theta节律活动的压抑以及由此引起的突触可塑性下调有关。     

刺激大鼠尾壳核对脑内脑啡肽含量的影响

为确定刺激某一脑区时,远隔脑区脑啡肽含量是否改变;如有改变,甲-脑啡肽和亮-脑啡肽的变化是否一致。本工作在乌拉坦麻醉大鼠上,用放射免疫测定方法测定了电刺激尾壳核对六个脑区(下丘脑、纹状体、丘脑、海马、皮层及脑干)两种脑啡肽含量的影响。放射免疫测定的结果表明:(1)动物经乌拉坦麻校舍醉及手术操作后,除纹状体外,其它五个脑区亮-脑啡肽含量均明显降低,甲-脑啡肽含量只有下丘脑和丘脑明显降低,其它脑区无显著变化。(2)在乌拉坦麻醉及手术的基础上,再刺激尾壳核,除丘脑无显著变化外,其它五个脑区甲-脑啡肽含量均明显降低,亮-脑啡肽含量均明显升高,甲-脑啡肽/亮-脑啡肽比值减少(其中纹状体的比值改变无统计学显著性)。以上结果表明,刺激大鼠尾壳核可明显影响远隔脑区脑啡肽含量。关于甲-脑啡肽和亮-脑啡肽反向变化的意义有待进一步研究。     

颞叶癫痫患者海马CA3和内嗅皮层网络的癫痫尖波对theta节律抑制作用的量化评估

海马CA3和内嗅皮层(entorhinal cortex,EC)网络是海马认知功能和颞叶癫痫研究的关键回路之一,尖波对海马网络theta(4~8 Hz)节律抑制作用的研究有利于揭示癫痫对认知功能影响的机制。以往,在网络层面上,该抑制作用常借助脑片来实现定量评估。本文旨在建立依赖于脑深度局部场电位评估癫痫尖波对theta节律抑制作用的方法。从4位术前处于快速眼球运动(rapid eyes movement,REM)睡眠下的颞叶癫痫患者皮质电极记录中择取发作间期有散发性尖波(sporadic spikes,SSs)脑电和两个相邻SSs间无尖波暂态期脑电,尖波分别只在CA3、只在EC、或在CA3和EC同步出现,应用Gabor小波和Hilbert变换计算尖波前后和无尖波暂态期theta能量,并计算无尖波暂态期theta节律的断裂程度。结果显示:(1)尖波可瞬时降低theta能量,CA3和EC同步尖波时下降最为剧烈,抑制作用最强;(2)无尖波暂态期theta能量下降,出现theta节律消失,造成节律断裂,表明抑制作用在持续,且断裂程度与尖波附近抑制作用一致;(3)3例患者无尖波暂态期theta能量水平降低程度与尖波附近抑制作用一致,而1例不一致。本文结果提示,SSs可对theta节律产生瞬时、直接的抑制作用,该抑制作用可在无尖波暂态期持续,并可由theta节律断裂程度反映。该工作首次应用局部场电位证明了癫痫尖波对theta节律抑制作用可通过无尖波时脑电节律的断裂程度来评估,为利用脑电衡量癫痫尖波抑制作用提供了量化分析方法。     

大鼠在体海马CA1区场电位引导新技术——刺激/记录/给药一体化装置的开发和应用

大鼠海马场电位记录是研究学习记忆的一个重要手段,尤以在体记录更具生理学意义.为克服目前在体海马场电位记录的弊端和诸多不便,提高实验效率,设计并完善了一套简便易行,融刺激、记录、给药于一体的大鼠海马在体CA1区场电位实验技术.将雄性SD大鼠麻醉后固定于脑立体定位仪上,利用自制的刺激/记录/给药联合装置,引导海马CA1区场兴奋性突触后电位(fEPSP).结果表明,使用刺激/记录/给药联合装置能长时间稳定记录由测试刺激诱发的海马CA1区fEPSP.高频刺激条件下,能成功诱导早期时相长时程增强(E-LTP)和晚期时相型长时程增强(L-LTP).海马内注射AMPA受体阻断剂CNQX(100μmol/L,1μl)可迅速抑制fEPSP,注射NMDA受体拮抗剂AP-5(100μmol/L,1μl)可明显压抑LTP,药物发挥作用的时间较侧脑室给药明显缩短,剂量减少.采用此联合装置还成功实现了PPF的稳定记录.总之,采用刺激/记录/给药一体化技术进行在体海马CA1区场电位记录的特点是简单、可靠、高效,可以为开展脑认知功能活动的电生理学研究奠定良好的基础.     

海马CA1区ripple节律相关高频放电中间神经元

通过在清醒小（Mus musculus）大脑同步记录海马区单神经元放电和场电位,发现在海马CAl区存在两类-9慢波睡眠时海马特征场电位“ripple”高频振荡（100-250Hz）相关的高频放电中间神经元．这两类神经元在慢波睡眠时的放电与ripple在时间上有高度同步性,对应每个ripple振荡波,它们都有一串高频放电．其中一类中间神经元（类型Ⅰ）在一个ripple振荡波的每个子振荡周期基本有1个放电,而另一类中间神经元（类型Ⅱ）则有1-2个放电．在ripple振荡波时段,这两类中间神经元的峰值放电频率分别高达310±33．17Hz（类型Ⅰ）和410±47．61Hz（类型Ⅱ）．动物清醒活动时,这两类中间神经元的放电与海马场电位的theta节律有锁相关系,它们的最大放电概率在theta节律的波谷段．给予动物摇晃刺激时,这两类中间神经元的放电频率均会短促增加．这些研究结果显示,海马CAl区的这种高频放电中间神经元参与调节海马神经元网络的整体活动状态．     

多通道在体记录技术——神经元放电与节律性场电位间的相位分析方法

本文旨在介绍神经元放电序列与节律性场电位间的相位分析方法。多通道在体记录技术能同时记录群体神经元和局部场电位的活动信号。神经元的放电活动一般表征为放电时间序列;而在局部场电位信号中,则包含有不同频率成分的周期性节律振荡。相位分析主要考察神经元放电时刻与周期性节律场电位相位间的相互关系。具体分析时,先运用Hilbert变换计算出某一频段节律场电位信号的瞬时相位值,然后再计算某一神经元放电序列中每个动作电位相对于该节律场电位的放电相位,最后通过考察这些放电相位的分布特性,来判断该神经元与该节律场电位相位间的放电相位关系。如一神经元放电序列对某种节律场电位的相位分布经统计检验不是随机的,则表明该神经元对这种节律场电位有放电锁相关系。Theta相位进动则是一种特殊的神经元放电与周期性节律场电位间的相位关系,也是海马位置细胞放电的基本特性之一。海马位置细胞在位置野内一般呈theta节律簇状放电模式,而相位进动是指每一theta波内放电的theta相位,相对上一theta波会逐渐提前。这一现象可通过对位置细胞放电的theta相位和动物实时位置使用线性模型来描述;并运用圆周线性相关分析法,计算它们之间的相关系数,从而研究位置细胞在位置野中的放电相对于theta相位的进动情况。通过相位分析,可以帮助我们了解神经元放电与节律性场电位信号间的时间信息编码特性。     

深度麻醉至脑死亡期间大鼠海马神经元活动的突变

全身麻醉若操作不当可能造成致命的中枢神经系统损伤,因此其安全性受到广泛关注.为了揭示麻醉不断加深的过程中神经元活动的变化规律,本文研究了大鼠在乌拉坦(urethane)深度麻醉至脑死亡期间海马区神经元兴奋性和信号传导功能的变化.利用微电极阵列记录和电刺激技术,在海马CA1区胞体层分别记录Schaffer侧支上正向刺激和海马白质上反向刺激诱发的群峰电位(population spike,PS).以PS的幅值和潜伏期为指标,分析海马神经元活动的变化.结果表明,随着乌拉坦血药浓度的增加,PS幅值逐渐减小,潜伏期逐渐延长,意味着乌拉坦抑制了神经元的兴奋性以及轴突传导和突触传递.特别是这些变化存在明显的转折点(即突变),将整个衰减过程分成慢变和快变2个阶段.快变期的剧烈衰减迅速导致脑死亡.而且,引起突变的决定性因素可能是乌拉坦的血药浓度,而非麻醉时间的长短.但是,当乌拉坦注射速率较慢时,延长的慢变期仍然会使神经元功能的受损加重.这些研究结果为动物实验的麻醉操作和临床麻醉的安全应用提供了重要的信息.     

电刺激大鼠坐骨神经诱发海马齿状回突触可塑性研究

观察电刺激大鼠坐骨神经引起海马齿状回诱发场电位的变化,探讨外周传入信息在海马的可塑性以及海马在痛觉调制中的作用。共记录了28只大鼠海马齿状回诱发场电位,平均幅度(23.73±1.12)μV,潜伏期(198.46±5.91)ms。不同条件刺激引起的反应包括:高频条件刺激使海马齿状回诱发场电位幅度降低;低频条件刺激使海马齿状回诱发场电位幅度增大。结果提示,电刺激坐骨神经可在海马齿状回记录到诱发场电位,不同的条件刺激可引起诱发场电位的不同变化,表现为突触传递效能增强或降低,海马对外周传入信息及痛觉起一定的调制作用。     

癫痫模型大鼠海马CA1网络theta节律断裂的观察*

目的:探究尖波间期和无尖波恢复期颞叶癫痫大鼠模型的海马CA1网络theta节律随癫痫发展进程的变化规律。方法:14只成年雄性Wistar大鼠(200～250 g)麻醉后开颅,在海马的背侧埋入一个双极性钢电极(直径小于1 mm),在颅骨上埋入三个不锈钢皮质电极,在左和右额皮质内分别植入两个电极,在小脑埋入参考电极,粘合颅骨,检测、记录大鼠脑电图;之后腹腔注射癫痫诱发药物,匹罗卡品氢氯化物(pilocarpine hydrochloride,310 mg/kg),30 min后给予大鼠莨菪碱 (scopolamine, 1 mg/kg);借助14只大鼠在嗅行(exploration)时脑深部记录(SEEG),应用Gabor小波时频能量分析估算断裂段数(以350 ms为1段),与总段数的比值定义为断裂比,用来衡量theta节律断裂程度,分别计算了癫痫发展进程的早期(D7)和晚期(D25)中两个邻近尖波之间时间段(定义为尖波间期)和随后无尖波恢复期theta节律断裂比,与注射前脑电图比较。结果:① 与对照脑电图比较,癫痫诱发大鼠的D7和D25的theta节律断裂比显著升高(P＜0.05),并且D7远高于晚期D25;② 在无尖波恢复期,theta节律断裂比与尖波间期相当 (P＜0.05)。结论:癫痫尖波直接导致了theta节律断裂,断裂程度将随癫痫发展进程而动态变化,早期伤害尤其严重。     

高脂饲养青春期大鼠电击回避反应和海马CA3区场电位的改变

目的：观察高脂饲养至青春期的大鼠对电击回避反应和海马CA3区实时局部场电位变化。方法：断乳1周幼鼠改用基础饲料和高脂饲料分别喂养4周至青春期,分为基础饲料组（BF组）和高脂饲料组（HFD组）,Y型迷宫电击回避训练方法,记录2组大鼠电击回避达学会标准的相关参数,同时无线遥测大鼠达标时海马CA3区实时局部场电位。结果：与BF组大鼠比较,HFD组大鼠体重明显增加,Y型迷宫电击回避训练1~2 d大鼠达标百分率、电击回避达标各项指标均略优于BF组;双侧海马CA3区局部场电位节律出现去同步化快波改变,右侧海马CA3区出现了θ波和γ 1波百分比的同步性增加,但无θ~γ 1波相位-振幅耦合出现。结论：幼年期短期高脂饮食至青春期的大鼠,尽管体重较基础饲料大鼠增加,但未见Y型迷宫电击回避反应能力和海马依赖性空间认知功能的减退。     

Impairment of Cognitive Function and Synaptic Plasticity Associated with Alteration of Information Flow in Theta and Gamma Oscillations in Melamine-Treated Rats

Changes of neural oscillations at a variety of physiological rhythms are effectively associated with cognitive performance. The present study investigated whether the directional indices of neural information flow (NIF) could be used to symbolize the synaptic plasticity impairment in hippocampal CA3-CA1 network in a rat model of melamine. Male Wistar rats were employed while melamine was administered at a dose of 300 mg/kg/day for 4 weeks. Behavior was measured by the Morris water maze(MWM)test. Local field potentials (LFPs) were recorded before long-term potentiation (LTP) induction. Generalized partial directed coherence (gPDC) and phase-amplitude coupling conditional mutual information (PAC_CMI) were used to measure the unidirectional indices in both theta and low gamma oscillations (LG, ∼30–50 Hz). Our results showed that melamine induced the cognition deficits consistent with the reduced LTP in CA1 area. Phase locking values (PLVs) showed that the synchronization between CA3 and CA1 in both theta and LG rhythms was reduced by melamine. In both theta and LG rhythms, unidirectional indices were significantly decreased in melamine treated rats while a similar variation trend was observed in LTP reduction, implying that the effects of melamine on cognitive impairment were possibly mediated via profound alterations of NIF on CA3-CA1 pathway in hippocampus. The results suggested that LFPs activities at these rhythms were most likely involved in determining the alterations of information flow in the hippocampal CA3-CA1 network, which might be associated with the alteration of synaptic transmission to some extent.     

Artificial Theta Stimulation Impairs Encoding of Contextual Fear Memory

Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4–12 Hz) and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous theta rhythm in amplitude and frequency. However, contrary to our predictions, artificial theta stimulation impaired conditioned fear response in both sham and fimbria-fornix lesioned animals. These data suggest that restoration of theta oscillation per se is not sufficient to support memory encoding after fimbria-fornix lesion and that universal theta oscillation in the hippocampus with a fixed frequency may actually impair memory.     

Optogenetically Induced Seizure and the Longitudinal Hippocampal Network Dynamics

Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.     

The Laminar Cortex Model: A New Continuum Cortex Model Incorporating Laminar Architecture

Local field potentials (LFPs) are widely used to study the function of local networks in the brain. They are also closely correlated with the blood-oxygen-level-dependent signal, the predominant contrast mechanism in functional magnetic resonance imaging. We developed a new laminar cortex model (LCM) to simulate the amplitude and frequency of LFPs. Our model combines the laminar architecture of the cerebral cortex and multiple continuum models to simulate the collective activity of cortical neurons. The five cortical layers (layer I, II/III, IV, V, and VI) are simulated as separate continuum models between which there are synaptic connections. The LCM was used to simulate the dynamics of the visual cortex under different conditions of visual stimulation. LFPs are reported for two kinds of visual stimulation: general visual stimulation and intermittent light stimulation. The power spectra of LFPs were calculated and compared with existing empirical data. The LCM was able to produce spontaneous LFPs exhibiting frequency-inverse (1/ƒ) power spectrum behaviour. Laminar profiles of current source density showed similarities to experimental data. General stimulation enhanced the oscillation of LFPs corresponding to gamma frequencies. During simulated intermittent light stimulation, the LCM captured the fundamental as well as high order harmonics as previously reported. The power spectrum expected with a reduction in layer IV neurons, often observed with focal cortical dysplasias associated with epilepsy was also simulated.     

Amino acids and the synaptic pharmacology of granule cells in the dentate gyrus of the rat

Granule cells in the dentate gyrus in the hippocampi of anaesthetized rats were excited by stimulation of the contralateral hippocampus (the commissural input) and the ipsilateral entorhinal cortex (the perforant path). The cells were also activated by the electrophoretic administration of various amino acids. A selective antagonism of glutamate and perforant path excitations was obtained with glutamic acid diethylester, and of aspartate and other amino acid induced and commissural excitations with D- or DL-alpha-aminoadipate. An excitatory effect of alpha-aminoadipate which was sometimes observed was prevented by the gamma-aminobutyric acid antagonist bicuculline, and may be a disinhibitory phenomenon. The results lend support to the proposition that the transmitter of the perforant path is glutamate while that of the commissural fibres is aspartate.     

Theta driving both inhibits and potentiates the effects of nicotine on dentate gyrus responses

The medial septal area of conscious rats was stimulated through previously implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta. Two weeks later in the anaesthetized rats the effects of a single subcutaneous injection of nicotine (0.4 mg x kg(-1)) on fEPSPs, evoked in the dentate gyrus by separate stimulation of the MPP and LPP, were studied and compared with those obtained in controls. Nicotine increased the firing of locus coeruleus neurones and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP stimulation. Prior theta driving considerably increased the effect of nicotine on the responses evoked by stimulation of the MPP and abolished the nicotine-induced potentiation of the responses evoked by stimulation of the LPP. The results are attributed to theta driving increasing the amount of noradrenaline released by nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting potentiation at the medial perforant path synapse and a long-lasting depression at the lateral perforant path synapse.     

Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus

Acetylcholine (ACh) influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2), was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB) of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT) promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs) in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs), and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs) of local field potentials (LFPs) were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach may be a useful complementary technique in future investigations of endogenous ACh effects.     

Electrical activity of the rat brain following antenatal hypoxia

EEG and EPs in the visual and parietal neocortical areas and the hippocampus were studied in freely behaving rats at the age of two-three months after antenatal hypoxia. Increase of spectral power in delta and theta bands and its decrease in alpha and beta bands in the background EEG and in responses to a protracted light stimulation were observed in experimental animals in comparison to control ones. The most pronounced changes were observed in the parietal cortex and hippocampus. The character of changes in latencies and the share of individual EP components recorded point to an accelerated excitation reverberation in neuronal networks in response to afferent stimuli and to a prolongation of after-discharges in the parietal cortex and hippocampus testifying to peculiarity of information processing in these brain structures. On the basis of other authors' data, certain parallelism is supposed to exist between the electrophysiological parameters in experimental animals and some groups of children with mental retardation.     

The electrophysiological characteristics and behavioral manifestations of hippocampal and thalamic spreading depression]

Behavioral manifestations of spreading depression (SD) were compared with SD electrophysiological characteristics in these structures. Carbon electrodes were suitable for recording DC slow potential changes in freely moving animal. It was shown that short (0.1 s) high-frequency (200 Hz) electrical stimulation of thalamus and hippocampus with intensity 50-300 microA easily triggered SD wave in these structures in narcotized and awake rats. The threshold of SD occurrence in dorsal hippocampus was the same or sometimes lower than that of the primary afterdischarge. Penetrating SD into ventral hippocampus provoked long latency seizure discharge and wet-dog shakings in awake rats. Intensity of locomotor activity accompanying bilateral hippocampal SD exceeded orienting response significantly. Contrary to hippocampus, thalamic SD was usually subseizure and unilateral phenomenon and had a clear tranquil effect on the rat locomotor activity. It was found that the rats didn't change the compartment preference after 20-45 SD waves in the thalamus or in the hippocampus.     

Theta phase coding in a network model of the entorhinal cortex layer II with entorhinal-hippocampal loop connections

We investigated successive firing of the stellate cells within a theta cycle, which replicates the phase coding of place information, using a network model of the entorhinal cortex layer II with loop connections. Layer II of the entorhinal cortex (ECII) sends signals to the hippocampus, and the hippocampus sends signals back to layer V of the entorhinal cortex (ECV). In addition to this major pathway, projection from ECV to ECII also exists. It is, therefore, inferred that reverberation activity readily appears if projections from ECV to ECII are potentiated. The frequency of the reverberation would be in a gamma range because it takes signals 20–30 ms to go around the entorhinal-hippocampal loop circuits. On the other hand, it has been suggested that ECII is a theta rhythm generator. If the reverberation activity appears in the entorhinal-hippocampal loop circuits, gamma oscillation would be superimposed on a theta rhythm in ECII like a gamma-theta oscillation. This is a reminiscence of the theta phase coding of place information. In this paper, first, a network model of ECII will be developed in order to reproduce a theta rhythm. Secondly, we will show that loop connections from one stellate cell to the other one are selectively potentiated by afferent signals to ECII. Frequencies of those afferent signals are different, and transmission delay of the loop connections is 20 ms. As a result, stellate cells fire successively within one cycle of the theta rhythm. This resembles gamma-theta oscillation underlying the phase coding. Our model also replicates the phase precession of stellate cell firing within a cycle of subthreshold oscillation (theta rhythm).