Modulation by adrenal steroids of limbic function

The effects of various steroid hormones on the long-term potentiation (LTP) of the rat hippocampus were evaluated. LTP was elicited in the dentate gyrus of adrenalectomized animals with priming tetanic stimulation (200 Hz-0.03 cps) of its main afferent, the perforant pathway. Single pulse EPSP (excitatory post-synaptic potential) slope, and PS (population spike) amplitude values were compared before and after the i.v. injection of the hormones and subsequently after the priming stimulation every 15 min up to 1 h. 18-OH-deoxycorticosterone (18-OH-DOC) produced a significant decrease of the EPSP LTP and arrested the PS enhancement in comparison with vehicle at every time post-tetanic stimulation. Its 21-acetate derivative produced a moderate decrease of the EPSP and had no effect on the PS LTP in comparison with vehicle. Deoxycorticosterone (DOC) exhibited similar effects on the EPSP although less marked than with 18-OH-DOC while the PS only decreased in the first 30 min post-train. Corticosterone decreased both EPSP and PS for the first 15 and 30 min after priming stimulation, respectively, matching values with those of vehicle afterwards. Its 21-acetate produced an initial decrease of the EPSP and had no effect on the PS LTP. Allo-tetrahydro-DOC produced little, if any, initial enhancement of the PS LTP in comparison with vehicle. These results show that the adrenal steroids tested can modulate hippocampal LTP, a plastic phenomenon in the mammalian CNS which is known to be related to memory and learning processes. Moreover, adrenal steroids can independently modify the PS or EPSP components of the LTP, suggesting different loci of action at the neuronal level.     

Effects of adrenocortical steroids on long-term potentiation in the limbic system: Basic mechanisms and behavioral consequences

Summary Hippocampal structures are a major target for adrenal steroid hormones, and hence these neural regions are some of the most likely mediators of the effects of adrenocortical steroids on behavior. Memory disturbance, in particular biasing toward negative contents, are part of the symptomatology presented by depressive patients. In turn, a sizeable subset of depression also presents with hypercortisolemia. Adrenocortical hormones are also known to affect memory processes. Hippocampal formatio is essential for declarative memory. We thought it appropriate then to study the effects of adrenal steroids on long-term potentiation, a putative memory mechanism in the hippocampus. Two clearly distinguished components of the evoked response to perforant path stimulation can be studied in the hippocampus: the excitatory postsynaptic potential (EPSP) which denotes the graded depolarization of the somadendritic region of the neuron and the population spike (PS), a manifestation of the all-or-none-discharge of the cell action potential. Corticosterone had a significant depressant effect on the EPSP component of the evoked response immediately and 15 min after injection. Thereafter EPSP amplitudes were within normal values. Corticosterone significantly decreased the PS immediately after the train, the component remaining low 30 min after the train. 5-Dihydrocorticosterone (a ring A-reduced metabolite of corticosterone) significantly reduced the PS component of the response at all times after injection. 18-Hydroxydeoxycorticosterone and deoxycorticosterone significantly decreased both EPSP and PS components of the evoked response from the time of infusion. Contrary to expectation, tetrahydrodeoxycorticosterone was ineffective in decreasing and if anything, enhanced the development of long-term potentiation. 18-Hydroxydeoxycorticosterone 21-acetate behaved like vehicle, except for the first 30 min after injection when the EPSP was decreased. Allotetrahydroprogesterone decreased all EPSP's values and had no effect in the PS development in comparison with vehicle. The suggestion is made that the study of steroidal effects on hippocampal LTP can serve as a preclinical model of some aspects of depression in a specific subset of the disease.     

Hippocampal Long-Term Potentiation Attenuated by Lesions in the Marginal Division of Neostriatum

The marginal division (MrD) is a spindled-neurons consisted zone at the caudal border of the neostriatum in the mammalian brain and has been verified as contributing to associative learning and declarative memory in the rat and human with behavior and functional magnetic resonance imaging methods. It was proved to have functional connections with the limbic system. Whether the MrD has influence on the hippocampal long-term potentiation (LTP) was investigated in this study. LTP was induced from the dentate gyrus (DG) in the hippocampus by high-frequency stimulation (HFS) to the perforant path (PP). The amplitude of the population spike (PS) and the slope of the excitatory postsynaptic potential (EPSP) increased significantly to form LTP in the DG of the hippocampus after HFS of PP in normal and saline-injected control groups of rats. Lesions introduced in the MrD reduced significantly both the amplitude of PS and the slope of the EPSP following HFS of the PP. The results indicated that lesions in the MrD could attenuate LTP formation in the hippocampus. Our data suggest that the MrD might very possibly have excitatory functional influence on the hippocampus and therefore might influence the function of the hippocampus.     

Effects of A1 and A2 Adenosine Receptor Antagonists on the Induction and Reversal of Long-Term Potentiation in Guinea Pig Hippocampal Slices of CA1 Neurons

1. Using simultaneous recordings of the field EPSP and the population spike in the CA1 neurons of guinea pig hippocampal slices, we confirmed that delivery of a high-frequency stimulation (tetanus: 100 pulses at 100 Hz) produced robust long-term potentiation of synaptic efficacy (LTP) in two independent components, a synaptic component that increases field excitatory postsynaptic potentials (EPSPs) and a component that results in a larger population spike amplitude for a given EPSP size (E-S potentiation).2. In the same cells, reversal of LTP (depotentiation; DP) in the field EPSP and in the E-S component is achieved by delivering low-frequency afferent stimulation (LFS:1 Hz, 1000 pulses) 20 min after the tetanus.3. When the tetanus or LFS was applied to CA1 inputs in the presence of an adenosine A₁ receptor antagonist, 8-cyclopentyltheophylline (1 M), the field EPSP was enhances in LTP and attenuated in DP, while the E-S relationship was not significantly affected in either LTP or DP.4. When similar experiments were performed using an A₂ receptor antagonist, CP-66713 (10 M), the field EPSP was blocked in LTP but facilitated in DP, while E-S potentiation was enhanced during both LTP and DP.5. The results show that endogenous adenosine, acting via A₁ or A₂ receptors, modulates both the synaptic and the E-S components of the induction and reversal of LTP. Based on the results, we discuss the key issue of the contribution of these receptors to the dynamics of neuronal plasticity modification in hippocampal CA1 neurons.     

Changes in the neuronal excitability of rat hippocampal slices isolated after destruction of the medial septal area]

To determine if electrophysiological properties of hippocampal pathways are altered after medial septal area (MSA) destruction, extracellular recordings were made from hippocampal slices of rats 30 days following lesion and compared with those from unoperated controls. The preparation of slices, data accumulation and data analyses were done under the same conditions. The electrophysiological parameters of interest were the population spike (PS) and the field EPSP, produced in the CA1 pyramidal layer by stimulation of the Schaffer collaterals. The principal finding of this study was that neuronal excitability in slices from MSA-lesioned rats was altered. The most striking abnormalities were an epileptiform activity, which consisted of multiple PSs, and multiple seizure-like after discharges with a delayed onset to low stimulation intensities. In the CA1 region of the slices collected from lesioned rats the input-output curve of field EPSP versus PS showed a leftward shift as compared with their counterparts in normal slices. These changes may be related to relative reduction of inhibitory processes in interneuronal circuits of CA1 region.     

C-Type natriuretic peptide modulates pre- and postsynaptic properties in hippocampal area CA1 in vitro

The cGMP producing natriuretic peptide receptor B (NPR-B) and its ligand C-type natriuretic peptide (CNP) are widely distributed in the brain and are highly expressed in the hippocampal regions CA1-CA3. To date only limited functional data is available concerning the physiological effects of the peptide hormone in the hippocampus. Therefore, we were interested in how bath application of the peptide hormone might influence synaptic plasticity following high frequency stimulation (HFS). We found that CNP application decreased the population spike (PS) amplitude after HFS, thereby affecting long-term potentiation (LTP) in acute hippocampal slices. To investigate the molecular consequences of CNP application leading to a decrease in PS amplitude, we further analyzed the impact of the hormone on the number of presynaptic synapsin I clusters and number of postsynaptic AMPA receptor subunit GluR1 clusters as well as their co-localization in a primary hippocampal cell culture system. The observed pre-and postsynaptic effects after CNP stimulation of the cGMP pathway in hippocampal cell cultures may underlie the effect of the peptide hormone on LTP.     

Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices

Using field potential recording in the CA1 region of the rat hippocampal slices, the effects of eugenol on synaptic transmission and long-term potentiation (LTP) were investigated. Population spikes (PS) were recorded in the stratum pyramidal following stimulation of stratum fibers. To induce LTP, eight episodes of theta pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS in a concentration-dependent manner. The effect was fast and completely reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that while eugenol depresses synaptic transmission it does not affect the ability of CA1 synapses for tetanus-induced LTP and plasticity.     

Effects of Chronic Stress and Phenytoin on the Long-term Potentiation （LTP） in Rat Hippocampal CA1 Region

Stress is the response to stimulation from inside andoutside with complicated effects on organisms. Appropri-ate stressful reactions are helpful in resisting diseases byactivating unspecific modulation system, while severe orprolonged stresses are harmful and even induce mentaland physical disorders such as recurrent depression, post-traumatic stress disorder (PTSD), Alzheimer’s disease andepilepsy [1]. Hippocampus, a main brain region of keyimportance for learning, memory and emotion, is t…     

大鼠海马CA3区的习得性长时程突触增强

本实验应用慢性埋植电极技术以电生理学结合行为学的方法,观察大鼠条件性饮水反应的建立、消退和再建立过程中,其海马CA_3区突触效应的变化规律。以刺激内嗅区的穿通纤维(PP)诱发的单突触的群体锋电位(PS)及群体兴奋性突触后电位(EPSPs)为指标,经叠加处理分析,发现随着条件反应的建立,海马CA_3锥体细胞出现突触效应的长时程增强(LTP),它随行为反应的实验性消退而消退,而在随后再次建立条件反应时,又重新出现;且无论此LTP达最高水平还是它的完全消退均超前于条件性行为反应的水平。又在一个实验日训练作业结束时PS并未立即随之增大,在24h内它随时间而发展,但到第4小时已达最高水平,且条件反应率是与PS的水平相应的,对PS与EPSPs的斜率进行相关分析表明,PS的变化主要是突触传递功效的变化。上述结果表明,海马CA_3区随着行为训练有习得性LTP产生。从其发神变化特点及其与条件性行为的关系,提示此习得性LTP极其可能是本实验中学习和记忆的展经基础。     

Low Dose ZD7288 Attenuates the Ischemia/Reperfusion-Induced Impairment of Long-Term Potentiation Induction at Hippocampal Schaffer Collateral-CA1 Synapses

Focal cerebral ischemia can impair the induction of activity-dependent long-term potentiation (LTP) in the hippocampus. This impairment of hippocampal synaptic plasticity can be caused by excitotoxicity and subsequent perturbation of hippocampal LTP-relevant transmitter systems, which include NR2B and PSD-95. It has been suggested that hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels may play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study has indicated that the selective HCN channel blocker ZD7288 can produce a dose-dependent inhibition of the induction of LTP at the Schaffer collateral-CA1 synapse of hippocampus by reducing the amount of glutamate released. It has also been demonstrated that ZD7288 can protect against neuronal injury caused by oxygen glucose deprivation. In the present study, we investigated the effect of ZD7288 on the induction of activity-dependent LTP and the expression of NR2B and PSD-95 after focal cerebral ischemia/reperfusion injury. The results showed that the induction of LTP was significantly impaired and the levels of NR2B and PSD-95 mRNA and protein were markedly decreased in the CA1 region of hippocampus following focal cerebral ischemia/reperfusion injury. Administration of low dose ZD7288 (0.25 μg) at 30 min and 3 h after the onset of ischemia attenuated the impairment of LTP induction and alleviated the NR2B and PSD-95 mRNA and protein down-regulation commonly induced by cerebral ischemia/reperfusion injury. These results suggest that low dose ZD7288 can ameliorate the ischemia/reperfusion-induced impairment of synaptic plasticity in the hippocampal CA1 region.     

Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region

The importance of well characterized calcium/calmodulin-dependent protein kinase (CaMK) II in hippocampal long term potentiation (LTP) is widely well established; however, several CaMKs other than CaMKII are not yet clearly characterized and understood. Here we report the activation of CaMKIV, which is phosphorylated by CaMK kinase and localized predominantly in neuronal nuclei, and its functional role as a cyclic AMP-responsive element-binding protein (CREB) kinase in high frequency stimulation (HFS)-induced LTP in the rat hippocampal CA1 region. CaMKIV was transiently activated in neuronal nuclei after HFS, and the activation returned to the basal level within 30 min. Phosphorylation of CREB, which is a CaMKIV substrate, and expression of c-Fos protein, which is regulated by CREB, increased during LTP. This increase was inhibited mainly by CaMK inhibitors and also by an inhibitor for mitogen-activated protein kinase cascade, although to a lesser extent. Our results suggest that CaMKIV functions as a CREB kinase and controls CREB-regulated gene expression during HFS-induced LTP in the rat hippocampal CA1 region.     

Quantal analysis of long-term potentiation of combined neuronal postsynaptic potentials on hippocampal slices in vitro

Excitatory postsynaptic potentials (EPSP) were recorded from 14 neurons in guinea pig hippocampal slices (area CAl) after stimulating the stratum radiatum (Schaffer collaterals) and stratum oriens. An increase occurring in EPSP amplitude in 7 units (9 pathways) recorded 15–45 min after tetanic stimulation of Schaffer collaterals is viewed as long-term potentiation (LTP). Statistical analysis conducted according to two sets of quantal theory (histogram and variance methods) showed an increase in mean quantal content (m) during LTP. An increase in quantal size, found only when using the histogram method, did not correlate with LTP level. This increase is thought to be associated with the considerably greater sensitivity of the histogram method to noise level in comparison with the variance method, the latter being more reliable with signals of high noise level. The increase found in m using both methods matches findings previously obtained for the whole brain; it also points to presynaptic location of mechanisms responsible for raised synaptic efficacy during LTP.Institute for Brain Research, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Max-Planck Institute of Biophysical Chemistry, Göttingen, West Germany. Institute of Zoology, Jagiellonian University, Cracow, Poland. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 465–472, July–August, 1990.     

Iron mediates N-methyl-D-aspartate receptor-dependent stimulation of calcium-induced pathways and hippocampal synaptic plasticity

Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-D-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP.     

脑发育不同阶段慢性铅暴露对大鼠在体海马齿状回LTP的影响

目的和方法：探讨脑发育不同阶段慢性铅暴露对在体海马ＬＴＰ的影响。应用细胞外微电极记录单脉冲刺激穿通路纤维在海马齿状回诱发的群体锋电位（ＰＳ）,观察母体期、断乳后及出生前后持续性慢性铅暴露大鼠于高频刺激（ＨＦＳ）前后的ＰＳ幅值变化,并与对照组相比较。结果：ＨＦＳ前,基线记录的各铅暴露组ＰＳ平均幅值及峰潜伏期与对照组无显著差异;ＨＦＳ后,各铅暴露组ＬＴＰ发生率虽与对照组无显著差异,但铅暴露组的ＬＴＰ增幅减小,并出现了短时增强转为抑制及ＬＴＤ型反应。统计显示各铅暴露组ＨＦＳ后ＰＳ振幅的平均增强率显著低于对照组：对照组平均增强至基线值的１３８．２％,母体期铅暴露组为基线值的１０８．８％,断乳后铅暴露组为基线值的１０７．８％,持续铅暴露组为基线值的１０４．４％。结论：脑发育任一阶段的慢性铅暴露均可损害海马ＬＴＰ的在体诱导和维持,且以维持过程受损为主;与发育成熟海马相比,未成熟期海马对铅的神经毒性更为敏感,突触可塑性更易受损。     

Suppression of "fast" IPSP,superposed on "slow", as a possible cause of priming in murine hippocampus

Intra- and extracellular response in area CA1 to stimulation of two independent afferent inputs, one a priming or conditioned and the other a test or primed input (C1 and C2, respectively) were recorded in surviving murine hippocampal slices. Duration and amplitude of test field potentials (FP) and of excitatory postsynaptic potentials (EPSP), were measured, as well as amplitude of "fast" and "slow" components of inhibitory postsynaptic potentials or stimulation varying between 0 and 1 sec. Conditioning brought about an increase in the duration of FP, in duration and amplitude of EPSP, and suppression of IPSP at intervals of between 50 and 500 msec peaking at 200 msec (i.e., priming effect). These changes correlated with level of IPSP_b in response to conditioned stimuli. The most pronounced effect could be seen in neurons manifesting hyperpolarizing IPSP in response to test stimuli. Suppression of test IPSP_a after superposition on IPSP_b is thought to bring about the increase in test FP and EPSP seen during priming.Institute for Brain Research, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 6, pp. 730–739, November–December, 1990.     

铝暴露对大鼠海马神经元长时程增强和Na+通道表达的影响

海马神经元长时程增强(LTP) 被认为与学习和记忆的形成有关.Na⁺在诱导 LTP产生的过程中十分重要.实验发现,慢性铝暴露可以影响大鼠海马神经元LTP的产生,随着铝暴露浓度的增加,LTP 的幅值逐渐降低.RT-PCR 法对大鼠海马神经元 9 种类型Na⁺ 通道（即 Nav1.1～Nav1.9）的 mRNA 进行检测发现,除 Nav1.4 和 Nav1.8 Na⁺通道 mRNA 在大鼠海马神经元中未见表达外,慢性染铝组大鼠海马神经元7种Na⁺ 通道 mRNA 表达均明显增高（P<0.05）.蛋白印迹法对一种脑型 Na⁺通道 (Nav 1.2) 蛋白检测证明, Na⁺通道蛋白表达亦明显升高.结果提示,铝进入神经元后,可能通过影响 Na⁺ 通道蛋白的表达而影响了突触后神经细胞的去极化,进而影响了LTP的诱导过程,从而预示铝的暴露可能损害大鼠学习和记忆能力.     

Modulation of learning and hippocampal, neuronal plasticity by repetitive transcranial magnetic stimulation (rTMS)

The influence of high-frequency repetitive transcranial magnetic stimulation (rTMS) on learning process in mice and on neuronal excitability of the hippocampal tissue obtained from stimulated animals were investigated. While the stimulation with rTMS at higher frequency (15 Hz) improved animals' performance in novel object recognition test (NOR), lower frequency (1 and 8 Hz) impaired the memory. The effect was observed when evaluated immediately after rTMS exposure and declined with time. In parallel to the results of behavioral test, there was a significant enhancement of the synaptic efficiency expressed as of the long-term potentiation (LTP) recorded from hippocampal slices prepared from the animals exposed to 15 Hz rTMS. The stimulation with 1 and 8 Hz had no influence on the magnitude of LTP. Our results demonstrate that rTMS modifies mechanisms involved in memory formation. The effects of rTMS in vivo are preserved and expressed in the hippocampus tested in vitro.     

低铅暴露对大鼠海马突触可塑性范围的影响

长时程增强(LTP)和长时程抑制(LTD),作为突触可塑性变化的两种主要形式,被认为是学习记忆的可能机制.突触可塑性范围可以定量的表征突触可塑性的变化.应用在体电生理技术,在同一只动物上记录LTP和LTD,研究了发育过程中慢性铅暴露对大鼠海马齿状回颗粒细胞突触可塑性范围和双脉冲易化的影响.对照组的LTP、LTD的幅度分别是187.9±6.2%(n＝7),85.2±1.6%(n＝7),而铅处理组分别为140.5±1.2%(n＝7),102.8±3.8%(n＝7).与对照组相比,铅处理组的LTP的幅度降低了47.4%,LTD的诱导几乎完全被铅损伤.先诱导出LTP后再通过低频刺激则可以在铅处理组诱导出LTD(81.5±2.2%(n＝7)),但远远小于对照组(66.8±4.3%(n＝7)).对照组突触可塑性范围是103.1±11.5%(n＝7),是铅处理组突触可塑性范围(37.7±9.6%(n＝7))的2.7倍.在对照组,双脉冲易化反应是从脉冲间隔20ms时开始,而铅处理组则是从50ms开始.当脉冲间隔为70ms时,两组的双脉冲易化幅度均达到最大值,但易化的强度有显著的差异,分别为211.6±32.2%(n＝7),11.1±26.9%(n＝7).结果表明铅显著地抑制了大鼠海马齿状回颗粒细胞的双脉冲易化效应,降低了双脉冲易化的间隔范围和突触可塑性范围.这可能是铅损伤学习记忆功能的机制之一.     

A Prosaposin-Derived Peptide Alleviates Kainic Acid-Induced Brain Injury

Four sphingolipid activator proteins (i.e., saposins A–D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.     

Quantal analysis of long-term posttetanic changes in minimal postsynaptic potentials of hippocampal slices in vitro

Minimal excitatory postsynaptic potentials (EPSP) were investigated in 13 neurons under single or double-pulse near-threshold microstimulation of the radial layer (Schaffer's collaterals) and stratum oriens in surviving hippocampal slices (area CA1) in guinea pigs. The amplitude of 23 EPSP (9 units; 12 pathways) rose after tetanization of Schaffer's collaterals over a 5–55 min period, taken as long-term potentiation (LTP). Statistical analysis conducted using four methods of quantal hypothesis based on a binomial approximation revealed an increase in mean quantal content (m) during LTP. The rise in quantal size was only statistically significant when using data obtained from a section of these methods (mainly for stretches of over 15 min following tetanization) and shows no correlation with intensity of LTP. The pronounced rise in m demonstrated using different methods matches data from experiments on intact animals and indicates a presynaptic location of the mechanisms underlying protracted persistence of residual tetanization lasting some tens of minutes.Institute for Brain Research, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany. Zoological Institute, Jagiellonian University, Cracow, Poland. Translated from Neirofiziologiya, Vol. 22, No. 6, pp. 752–761, November–December, 1990.