FK506对大鼠脑液压伤后神经行为和记忆的影响

目的 研究FK506对大鼠脑液压伤后神经行为和记忆的影响。方法 通过液压损伤法建立大鼠脑损伤模型,随机分为损伤组、治疗组和对照组(每组8只)。采用免疫组化方法和图象分析技术,检测突触素在皮质、海马和基底节的表达,并用流式细胞仪法检测上述部位的凋亡细胞数。结果 治疗组神经行为与记忆实验成绩高于损伤组。治疗组海马CA1、CA3区突触素表达显著增高(P<0.01)。海马、基底节和皮质的凋亡细胞数较损伤组明显减少。结论 FK506能促进突触素表达,减少海马和皮质细胞凋亡,有利于促进脑损伤后神经行为和记忆的恢复。     

大鼠脑缺血后海马CA1区胶质纤维酸性蛋白表达与迟发性神经元死亡的关系

目的观察大鼠大脑缺血再灌注后海马CA1区胶质纤维酸性蛋白(GFAP)的表达与迟发性神经元死亡的关系。方法采用大鼠大脑中动脉阻塞再灌注模型(MCAO),将大鼠随机分为MCAO后3d、7d、30d组及假手术组,应用免疫荧光与TUNEL染色法分别观察脑缺血再灌注后不同时间点缺血侧海马CA1区GFAP表达情况和迟发性神经元死亡(DND)的变化。结果(1)3d组海马DND阳性(DND 组)的MCAO大鼠、海马DND阴性(DND-组)的MCAO大鼠与假手术组大鼠比较,缺血侧海马CA1区GFAP染色的平均光密度无显著性差异(P>0.05),但GFAP阳性细胞的形态发生变化;(2)7d组大鼠缺血侧海马CA1区GFAP阳性细胞大量活化增殖,表现为胞体变大,突起增多;DND( )、DND(-)组海马CA1区GFAP染色的平均光密度较假手术组增高(P<0.01),且DND(-)组的GFAP平均光密度较DND( )组明显增高(P<0.01);(3)30d组大鼠缺血侧海马CA1区GFAP表达呈瘢痕样改变,DND( )、DND(-)组与假手术组比较其GFAP染色的平均光密度明显增高(P<0.05),且DND( )组的GFAP平均光密度较DND(-)组明显增高(P<0.05)。结论大鼠MCAO后星形胶质细胞反应性变化的差异可能与海马CA1区迟发性神经元死亡的发生有关。     

外伤后癫痫大鼠脑内突触素和苔藓纤维的观察

目的 通过研究液压脑损伤后突触索和苔藓纤维在外伤后癫痫和非癫痫的大鼠脑内的不同变化,以探讨外伤后癫痫的发病机制.方法 应用液压脑损伤复制脑损伤动物模型并记录脑电图和行为学变化,3个月后应用突触素免疫组织化学、Timm染色和汁算机图像分析技术分析皮质区突触索及海马区苔鲜纤维的不同变化.结果 突触素在皮质损伤区表达癫痫组(n=11)高于非癫痫组(n=20,P<0.05),苔藓纤维出芽在癫痫组CA3区始层明显增多(P<0.05).结论 突触素的表达增强和苔藓纤维出芽与外伤后癫痫天系密切,因果关系有待进一步研究.     

神经节苷脂GM1对大鼠脑液压伤后行为和记忆的影响

目的:探讨大鼠脑液压伤后GM1与学习记忆、脑内一氧化氮、突触素和细胞凋亡的关系.方法:液压损伤法建立大鼠脑损伤模型,随机分为治疗组、损伤组和对照组.观察伤后学习记忆改变,检测一氧化氮合酶(NOS)、一氧化氮(NO)、突触素和海马、皮质及基底节区细胞凋亡指数.结果:治疗组学习记忆成绩高于损伤组,NOS、NO明显降低,治疗组海马CA1区突触素显著增多,皮质、海马和基底节的凋亡细胞数明显减少.结论:GM1能减少海马和皮质细胞凋亡,可能有利于促进脑损伤后神经行为和记忆的恢复.     

颅脑创伤后大鼠海马CA1锥体细胞内在电生理和兴奋性突触传递特性的变化

目的 在细胞及突触水平探讨外伤后癫痫的发病机制.方法 自由落体致伤法制备大鼠颅脑创伤模型,采用膜片钳技术监测海马CA1区锥体细胞内在电生理特性和局部突触兴奋性的变化.结果 颅脑创伤后,大鼠CA1锥体细胞膜输入阻抗和时间常数增加,动作电位的阈电流降低；给予配对刺激后,海马CA1区兴奋性突触后电流表现为配对脉冲比率的降低及配对脉冲易化向配对脉冲抑制的转变.结论 颅脑创伤后海马CA1区神经元内在兴奋性和突触传递功能增强,这些改变可能是外伤后癫痫发病的重要原因.     

神经节苷脂GMl对大鼠脑液压伤后行为和记忆的影响

目的探讨大鼠脑液压伤后GM1与学习记忆、脑内一氧化氮、突触素和细胞凋亡的关系.方法液压损伤法建立大鼠脑损伤模型,随机分为治疗组、损伤组和对照组.观察伤后学习记忆改变,检测一氧化氮合酶(NOS)、一氧化氮(NO)、突触素和海马、皮质及基底节区细胞凋亡指数.结果治疗组学习记忆成绩高于损伤组,NOS、NO明显降低,治疗组海马CA1区突触素显著增多,皮质、海马和基底节的凋亡细胞数明显减少.结论GM1能减少海马和皮质细胞凋亡,可能有利于促进脑损伤后神经行为和记忆的恢复.     

GABAB受体对大鼠海马CA1区锥体细胞突触传递的作用

目的研究激活GABA_B受体对大鼠海马CA1区锥体细胞突触传递的影响。方法对成年大鼠海马脑片CA1区锥体细胞采用“盲法”全细胞电压钳记录,分别检测和分析巴氯芬(10μmol/L)对自发性的兴奋性突触后电流(EPSCs)和抑制性突触后电流(IPSCs)的影响。结果巴氯芬可显著降低符氨酸能EPSCs和γ-氨基丁酸能IPSCs的频率(P＜0．01),各自达58%±7%(n=17)和42%±10%(n=15),而对它们的幅度无显著性影响。结论巴氯芬对海马CA1区锥体细胞EPSCs和IPSCs的抑制作用属于突触前抑制,推测GABA_B受体所介导的这种抑制作用对CA1区神经元兴奋性的传出具有抑制作用,从而对癫痫的产生有控制作用。     

雌二醇对血管性痴呆大鼠海马CA1区GFAP表达的影响

目的研究17β-雌二醇对血管性痴呆(vascular dementia,VD)大鼠海马CA1区GFAP表达的影响,探讨雌激素对血管性痴呆大鼠中枢神经系统保护作用的机制。方法采用结扎双侧颈总动脉方法制备血管性痴呆动物模型,腹腔注射不同剂量17β-雌二醇60d后,应用Y迷宫检测各组VD大鼠认知功能以及免疫组化法等检测大鼠大脑海马CA1区GFAP表达的变化。结果腹腔注射17β-雌二醇60d后,大鼠认知功能显著改善;学习、记忆功能测试30次的正确次数较实验对照组明显增高(P<0.05),造模60d后的大鼠,其脑内CA1区GFAP免疫阳性细胞数较假手术组显著增高,而雌二醇组大鼠CA1区GFAP免疫阳性细胞数较实验对照组显著减少。结论雌激素补充疗法能选择性影响血管性痴呆大鼠脑内CA1区GFAP阳性细胞,并有可能影响学习和记忆能力。     

亚低温对大鼠脑创伤后海马区凋亡相关蛋白表达的影响

目的观察亚低温对大鼠创伤性脑损伤(TBI)后海马CA3区细胞凋亡及相关蛋白Bcl-2、Bax及Caspase-3表达的影响,探讨亚低温脑保护的分子生物学机制.方法将大鼠随机分成假手术、单纯脑损伤和脑损伤后亚低温治疗3组,应用改良Marmarou方法制作大鼠TBI模型,分别用流式细胞仪(FCM)和免疫组化法检测各组动物脑海马CA3区细胞凋亡率和Bcl-2、Bax及Caspase-3蛋白的表达.结果与假手术组相比,大鼠TBI后海马CA3区细胞凋亡率及Caspase-3表达增高(P<0.05),Bcl-2/Bax表达比下降(P<0.05).亚低温治疗后,大鼠脑海马CA3区细胞凋亡率及Caspase-3表达较单纯脑损伤组降低(P<0.05),而Bcl-2/Bax表达比升高(P<0.05).结论亚低温对TBI的脑保护作用机制可能与干预伤后凋亡相关基因表达并减少神经细胞凋亡有关.     

慢性脑缺血老龄大鼠海马中突触素的表达特征

目的 研究老龄大鼠慢性脑缺血后大脑海马中突触素表达特征.方法 应用免疫组化染色技术检测大鼠脑海马中CA1区、CA3区和齿状回中突触素的表达.结果 缺血组海马CA1区、CA3区和齿状回三处突触素灰度值均低于对照组,差异有统计学意义(P<0.05.结论 老龄大鼠海马结构内CA1区、CA3区及齿状回内突触素和NR2B的表达明显减少.     

Isoproterenol increases the phosphorylation of the synapsins and increases synaptic transmission in dentate gyrus, but not in area CA1, of the hippocampus.

Previous studies have shown that either norepinephrine (NE) or isoproterenol (ISO) enhances the slope of the field excitatory postsynaptic potential (EPSP) in the dentate gyrus of the rat hippocampal formation. In contrast, NE and ISO cause no increase in excitatory transmission in area CA1 of the hippocampus. The molecular mechanism underlying this brain region-specific increase in synaptic transmission is not known. The phosphorylation of synapsin I and synapsin II, two homologous presynaptic vesicle-associated proteins, is thought to promote neurotransmitter release. The authors have observed previously NE- and ISO-enhanced phosphorylation of synapsins I and II in the dentate gyrus. The purpose of this study was to determine whether ISO-stimulated phosphorylation also occurs in the CA1, where ISO has no effect on excitatory neurotransmission. These studies were correlated with electrophysiological studies in in vitro hippocampal slices. Superfusion of slices with ISO resulted in an increase in EPSP slope in the dentate but not in area CA1. The enhanced dentate EPSP returned to baseline levels within 30 minutes of washout of the drug. Isoproterenol produced corresponding increases in the phosphorylation of the synapsins in dentate slices but had no effect on these proteins in CA1 slices. Moreover, in dentate slices exposed to a 30-minute wash following incubation with ISO, phosphorylation of the synapsins returned to control levels. This close temporal and brain regional correlation between ISO stimulation of both synapsin phosphorylation and synaptic transmission suggests that the synapsin proteins may play a role in the synaptic potentiation produced by ISO in the dentate.     

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral-CA1, temporoammonic-CA1, and perforant pathway-dentate gyrus synapses along the longitudinal axis of the hippocampus

We aimed to study how morphine affects synaptic transmission in the dentate gyrus and CA1 regions along the hippocampal long axis. For this, recording and measuring of field excitatory postsynaptic potentials (fEPSPs) were utilized to test the effects of repeated morphine exposure on paired-pulse evoked responses and long-term potentiation (LTP) at Schaffer collateral-CA1 (Sch-CA1), temporoammonic-CA1 (TA-CA1) and perforant pathway-dentate gyrus (PP-DG) synapses in transverse slices from the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus in adult male rats. After repeated morphine exposure, the expression of opioid receptors and the α1 and α5 GABA_A subunits were also examined. We found that repeated morphine exposure blunt the difference between the DH and the VH in their basal levels of synaptic transmission at Sch-CA1 synapses that were seen in the control groups. Significant paired-pulse facilitation of excitatory synaptic transmission was observed at Sch-CA1 synapses in slices taken from all three hippocampal segments as well as at PP-DG synapses in slices taken from the VH segment in the morphine-treated groups as compared to the control groups. Interestingly, significant paired-pulse inhibition of excitatory synaptic transmission was observed at TA-CA1 synapses in the DH slices from the morphine-treated group as compared to the control group. While primed-burst stimulation (a protocol reflecting normal neuronal firing) induced a robust LTP in hippocampal subfields in all control groups, resulting in a decaying LTP at TA-CA1 synapses in the VH slices and at PP-DG synapses in both the IH and VH slices taken from the morphine-treated rats. In the DH of morphine-treated rats, we found increased levels of the mRNAs encoding the α1 and α5 GABA_A subunits as compared to the control group. Taken together, these findings suggest the potential mechanisms through which repeated morphine exposure causes differential changes in circuit excitability and synaptic plasticity in the dentate gyrus and CA1 regions along the hippocampal long axis.     

Synaptic reorganization in explanted cultures of rat hippocampus

Due to loss of afferent innervation, synaptic reorganization occurs in organotypic hippocampal slice cultures. With extra- and intracellular recordings, we confirm that the excitatory loop from the dentate gyrus (DG) to CA3 and further to CA1 is preserved. However, hilar stimulation evoked antidromic population spikes in the DG which were followed by a population postsynaptic potential (PPSP); intracellularly, an antidromic spike with a broad shoulder or EPSP/IPSP sequences were induced. Synaptic responses were blocked by glutamate receptor antagonists. Stimulation of CA1 induced a PPSP in DG. Dextranamine stained pyramidal cells of CA1 were shown to project to DG. After removal of area CA3, DG's and mossy fibers' (MF) stimulation still elicited PPSPs and EPSP/IPSP sequences in area CA1 which disappeared when a cut was made through the hippocampal fissure. During bicuculline perfusion, hilar stimulation caused EPSPs in granule cells and spontaneous and evoked repetitive firing appeared even after its isolation from areas CA3 and CA1. Collateral excitatory synaptic coupling between granule cells was confirmed by paired recordings. Besides the preservation of the trisynaptic pathway in this preparation, new functional synaptic contacts appear, presumably due to MF collateral sprouting and formation of pathways between areas CA1 and DG.     

Activity-induced decrease in early and late inhibitory synaptic conductances in hippocampus

The use dependence of inhibitory postsynaptic potentials (IPSPs) and their underlying conductances was studied in area CA1 of the hippocampal brain slice preparation, using a two-pulse paradigm in which paired activation of two separate synaptic inputs resulted in changes in the second, or "primed" response. In intracellular current-clamp recordings, the "primed" response, normally triphasic, exhibited a larger, wider excitatory PSP (EPSP) component and greatly reduced or absent IPSP components. Maximal widening occurred when the interval between synaptic stimuli was between 200 and 250 msec. Hyperpolarization of the postsynaptic cell reversed both the early IPSP and the direction of change of the width of the "primed" EPSP response, suggesting that the changes in the "primed" waveform were not due to the addition of an unidentified inward current(s). Furthermore, the reduction of the IPSPs during the "primed" response could not be accounted for by the fact that the membrane potential of the postsynaptic cell was hyperpolarized and therefore closer to IPSP reversal potential. Using single-electrode voltage-clamp techniques, we found that the early inhibitory conductance generally decreased by approximately 50%, with little if any change in reversal potential. The late inhibitory conductance also showed a priming-induced decrease of approximately 95%. Finally, "primed" four-pulse bursts of stimuli induced a larger depolarization in the postsynaptic cell than did unprimed bursts, also with an optimal interval of about 250 msec. We conclude that activation of certain synaptic pathways in the hippocampus results in a temporal window of 200-300 msec during which inhibitory synaptic activity is depressed and excitatory synaptic transmission is maximally effective, especially if the excitation occurs in short bursts. Such a mechanism would endow the inhibitory synaptic components of the hippocampus with a "gating" function to control long-term synaptic modification at excitatory synapses in the same region.     

Alterations in synaptic transmission and plasticity in area CA1 of adult hippocampus following developmental hypothyroidism

Transient reductions in thyroid hormone during critical periods of brain development can have devastating and irreversible effects on neurological function. The hippocampus is a brain region sensitive to thyroid hormones and is a necessary substrate for some forms of learning and memory. Subregions within the hippocampus display distinct ontogenetic profiles and have shown differential vulnerability to some indices of thyrotoxic insult. Synaptic function can be readily assessed in the hippocampus, yet little information exists on the consequences of early thyroid hormone insufficiency on the neurophysiological integrity of this structure. Previous work has examined the long-term consequences of perinatal hypothyroidism on neurophysiology of the dentate gyrus of the hippocampal formation. The current study reveals that alterations in synaptic function also exist in area CA1, and some differences in the pattern of effects are evident between the two hippocampal subfields. Developing rats were transiently exposed to the thyrotoxicant, propylthiouracil (PTU; 0 or 15 ppm), through the drinking water of pregnant dams beginning on gestational day 18. This regimen markedly reduced circulating levels of thyroid hormones and stunted pup growth. PTU exposure was terminated on postnatal day (PN) 21 and electrophysiological assessments were conducted by recording field potentials in area CA1 of hippocampal slices derived from adult male offspring. Synaptic transmission, short-term, and long-term synaptic plasticity were assessed. Consistent with observations in the dentate gyrus, somatic population spike amplitudes were reduced in assessments of baseline synaptic transmission of slices from PTU-exposed animals. No differences were identified in excitatory postsynaptic potentials (EPSP). Short-term plasticity of the EPSP as indexed by paired pulse facilitation was markedly impaired by PTU exposure. Long-term potentiation (LTP) of the population spike was enhanced, consistent with findings in dentate gyrus, but no change in EPSP LTP was detected. Perturbations in synaptic function in the hippocampus of adult rats transiently exposed to a period of hormone insufficiency during the perinatal period are likely to contribute to cognitive deficits associated with developmental hypothyroidism.     

Development of inhibitory and excitatory synaptic transmission in the rat dentate gyrus

We studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired-pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired-pulse responses across a wide range of interpulse intervals (IPI). Paired-pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN > 60. The synaptic paired-pulse profile (10–5,000 ms IPI) matured by PN7/8. The triphasic pattern of short-latency depression, a relative facilitation at intermediate intervals, and long-latency depression was present at all ages tested. Paired-pulse effects on granule cell discharge indicated the presence of weak short-latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short-latency inhibition was statistically equivalent to the mature dentate gyrus. Long-latency (500–2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40–120 ms) where spike facilitation was significantly depressed in the developmental groups. The studies indicate that short-term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early age. © 1994 Wiley-Liss, Inc.     

Sensory modulation of hippocampal transmission. I. Opposite effects on CA1 and dentate gyrus synapsis

Neuronal transmission through hippocampal subfields exhibits a high degree of modulation and appears dependent on the behavioral state and hippocampal EEG. Sensory inputs, which profoundly modify the hippocampal EEG, may be involved in modulating hippocampal excitability. Field responses of the CA1 region, evoked by ipsilateral CA3 or perforant path stimulation, as well as dentate gyrus potentials evoked by perforant path stimulation were recorded in paralyzed and locally anesthetized rats and studied before, during and after sensory stimulation, consisting of gentle stroking of the animal's fur. On some occasions the CA1 was also antidromically driven from the posterior alveus in order to study the recurrent inhibitory loop and paired pulses were applied to the perforant pathway to study recurrent inhibition in the dentate gyrus. Evoked responses were averaged and field excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude measured. In addition the positive wave which follows the population spike, which corresponds in part to the recurrent IPSP, was also evaluated. Sensory stimulation, which evoked a high-amplitude 5-6 Hz theta (theta)-rhythm in the hippocampal EEG, drastically depressed the efficacy of Schaffer collateral volleys in discharging the CA1 cells. The EPSP-PS curves, however, were not altered revealing that cellular excitability was unaffected. The inhibitory CA1 loop appeared to be unaltered. In contrast, the dentate gyrus responses to perforant pathway stimulation were enhanced during periods of sensory stimulation and the cellular excitability increased, as judged by the shift to the left of EPSP-PS relation. In addition, the recurrent inhibition appeared to be reduced during sensory stimulation. Present results demonstrate that sensory stimulation causes modulation of information transfer through the hippocampus. This modification of hippocampal transmission may serve to properly gate the information reaching the CA1 and dentate gyrus.     

Hippocampal kindling induced paired-pulse depression in the dentate gyrus and paired-pulse facilitation in CA3

Rats received high frequency (100 Hz, 1 s) hippocampal stimulations that evoked afterdischarges (ADs) in a partial kindling model of epilepsy. Kindled rats were given 15 ADs over 3 days. Control rats received the same stimulation pulses at 0.17 Hz (low frequency stimulation, LFSs). Subsequent to in vivo stimulations, hippocampal slices were obtained from the rats and extracellular field responses were recorded in the CA3 cell layer following CA1 stratum radiatum stimulation, and in the granule cell layer of the dentate gyrus (DG) following perforant path stimulation. At the DG, the paired-pulse facilitation of the population spike was depressed in the kindled than the control group, on 1 day or 23 days post ADs/LFSs. The excitatory postsynaptic potential (EPSP) responses in DG following single or paired pulses were not different between kindled and control slices. At CA3, paired-pulse facilitation of both the population spike and the population EPSP was increased in the kindled compared to the control group.     

Suppression of excitatory synaptic transmission can facilitate low-calcium epileptiform activity in the hippocampus in vivo

It has been reported that the inhibitory postsynaptic potential (IPSP) is abolished before the excitatory postsynaptic potential (EPSP) when the extracellular concentration of Ca(2+) ([Ca(2+)](o)) is removed gradually in hippocampal slices. However, the low-Ca(2+) nonsynaptic epileptiform activity does not appear until the [Ca(2+)](o) is decreased to a level sufficient to depress the excitatory synaptic transmission. This suggests the hypothesis that the suppression of excitatory synaptic transmission itself could facilitate the generation of epileptiform activity. In the present study, we tested this hypothesis and developed a new model of nonsynaptic epileptiform activity by gradually raising the neuronal excitability and blocking the synaptic transmission with high K(+), zero Ca(2+) and calcium chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the CA1 region of hippocampus in vivo. The changes of synaptic transmission and recurrent inhibitory activity during this process were evaluated by measuring the amplitude of the population spikes (PS) in response to paired-pulse orthodromic stimulation. The results show that the epileptiform activity appeared only when the excitatory synaptic transmission was depressed by further lowering [Ca(2+)](o) with EGTA. Similar epileptiform activity could be induced when EGTA was replaced by the excitatory postsynaptic amino acid antagonists D-(-)-2-amino-5-phosphonopentanoic acid (APV) plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) or APV alone but not DNQX alone. The combination application of APV and cadmium enhanced the epileptiform activity. These results suggest that the suppression of excitatory synaptic transmission can facilitate the appearance of epileptiform activity in solution with high K(+) and low Ca(2+) in vivo. These data provide new information to be considered in the development of antiepileptic drugs. They also suggest a possible mechanism to explain the fact that low-frequency electrical stimulation can suppress epileptiform activity.     

Lateral entorhinal,perirhinal, and amygdala-entorhinal transition projections to hippocampal CA1 and dentate gyrus in the rat: A current source density study

In urethane-anesthetized rats, cortical regions which provide distal dendritic excitation of the dentate gyrus and CA1 of the dorsal hippocampus were studied using current source density analysis. Electrical stimulation of the lateral perforant path (LPP) in the lateral angular bundle, lateral entorhinal cortex (LEC), and amygdala-entorhinal transition (TR) resulted in a current sink in the outer molecular layer of the dentate gyrus accompanied by proximal sources; this sink-source pattern is distinctly different from the source-sink-source pattern evoked by medial perforant path stimulation. The progressive decrease of the sink latency following stimulation of the TR, LEC, and LPP (11.6, 7.8, and 3.6 ms, respectively, at the dorsal blade of the dentate gyrus) suggests a possible sequence of orthodromic activation of these structures. Stimulation of the LEC or TR (collectively termed cortical stimulation) differed from LPP (fiber) stimulation. A low threshold and small chronaxie were characteristic of fiber rather than cortical stimulation. In addition, cortical stimulation, possibly through excitation of intracortical circuits, evoked larger paired-pulse facilitation of the excitatory postsynaptic currents in dentate gyrus and more symmetric excitation of the dorsal and ventral blades of the dentate gyrus as compared to fiber stimulation. Stimulation of the perirhinal cortex (PRh) evoked a short-latency sink in the outer molecular layer of the dentate gyrus with no paired-pulse facilitation, similar to fiber stimulation. A distal dendritic CA1 sink was observed after LPP but not after PRh stimulation. An ibotenic acid injection that lesioned almost all the cells in the perirhinal cortex confirmed the hypothesis that PRh stimulation activated fibers of passage, perhaps in the rostral ventrolateral angular bundle. We conclude that the PRh does not provide a significant excitatory input to the DG or CA1. We have found distinct dendritic excitation of the dentate gyrus by the lateral versus medial perforant paths, and by fiber (LPP and MPP) versus cortical (LEC and TR) stimulation. We also emphasize that processing in the entorhinal cortex is important in the temporal shaping of the signals afferent to the hippocampus. Hippocampus 1997;7:643–655. © 1997 Wiley-Liss, Inc.