Carbenoxolone depresses spontaneous epileptiform activity in the CA1 region of rat hippocampal slices

An important contributor to the generation of epileptiform activity is the synchronization of burst firing in a group of neurons. The aim of this study was to investigate whether gap junctions are involved in this synchrony using an in vitro model of epileptiform activity. Hippocampal slices (400 μm) were prepared from female Sprague–Dawley rats (120–170 g). The perfusion of slices with a medium containing no added magnesium and 4-aminopyridine (50 μM) resulted in the generation of spontaneous bursts of population spikes of a fast frequency along with less frequent negative-going bursts. The frequency of the bursts produced was consistent over a 3 h period. Carbenoxolone (100 μM), a gap junction blocker and mineralocorticoid agonist, perfused for 75 min, reduced the frequency of both types of spontaneous burst activity. Perfusion of spironolactone (1 μM), a mineralocorticosteroid antagonist, for 15 min prior to and during carbenoxolone perfusion did not alter the ability of carbenoxolone to depress the frequency of spontaneous activity. The incubation of hippocampal slices in carbenoxolone prior to recording increased the time taken for the spontaneous activity to start on change to the zero magnesium/4-aminopyridine medium and decreased the total number of spontaneous bursts over the first 60 min period.

The ability of carbenoxolone to delay induction of epileptiform activity and reduce established epileptiform activity suggests that gap junctions contribute to the synchronization of neuronal firing in this model.     

Tetanus toxin induces long-term changes in excitation and inhibition in the rat hippocampal CA1 area

Intrahippocampal tetanus toxin induces a period of chronic recurrent limbic seizures in adult rats, associated with a failure of inhibition in the hippocampus. The rats normally gain remission from their seizures after 6-8 weeks, but show persistent cognitive impairment. In this study we assessed which changes in cellular and network properties could account for the enduring changes in this model, using intracellular and extracellular field recordings in hippocampal slices from rats injected with tetanus toxin or vehicle, 5 months previously.In CA1 pyramidal neurones from toxin-injected rats, the slope of the action potential upstroke was reduced by 32%, the fast afterhyperpolarisation by 32% and the slow afterhyperpolarisation by 54%, suggesting changes in voltage-dependent conductances. The excitatory postsynaptic potential slope was reduced by 60% and the population synaptic potential slope was reduced at all stimulus intensities, suggesting a reduced afferent input in CA1. Paired-pulse stimulation showed an increase of the excitability ratio and an increase of cellular excitability only for the second pulse, suggesting a reduced inhibition. The polysynaptic inhibitory postsynaptic potential was reduced by 34%, whereas neither the inhibitory postsynaptic potential at subthreshold stimulus intensities,nor the pharmacologically isolated monosynaptic inhibitory postsynaptic potential were different in toxin-injected rats, suggesting a reduced synaptic excitation of interneurones. Stratum radiatum stimuli in toxin-injected rats, and not in controls, evoked antidromic activation of CA1 neurones, demonstrating axonal sprouting into areas normally devoid of CA1 pyramidal cell axons.We conclude that this combination of enduring changes in cellular and network properties, both pro-epileptic (increased recurrent excitatory connectivity, reduced recurrent inhibition and reduced afterhyperpolarisations) and anti-epileptic (impaired firing and reduced excitation), reaches a balance that allows remission of seizures, perhaps at the price of persistent cognitive impairment.     

Na+/Ca2+ exchanger activity induces a slow DC potential after in vitro ischemia in rat hippocampal CA1 region

In rat hippocampal CA1 neurons recorded intracellularly from tissue slices, a rapid depolarization occurred approximately 5 min after application of ischemia-simulating medium. In extracellular recordings obtained from CA1 region, a rapid negative-going DC potential (rapid DC potential) was recorded, corresponding to a rapid depolarization. When oxygen and glucose were reintroduced after generating the rapid depolarization, the membrane further depolarized and the potential became 0 mV after 5 min. Contrary, the DC potential began to repolarize slowly and subsequently a slow negative-going DC potential (slow DC potential) occurred within 1 min. A prolonged application of ischemia-simulating medium suppressed the slow DC potential. Addition of a high concentration of ouabain in normoxic medium reproduced a rapid but not a slow DC potential. The slow DC potential was reduced in low Na+- or Co2+-containing medium, but was not affected in low Cl-, high K+ or K+-free medium, suggesting that the slow DC potential is Na+-and Ca2+-dependent. Ni2+ (Ca2+ channel blocker as well as the Na+/Ca2+ exchanger blocker) and benzamil hydrochloride (Na+/Ca2+ exchanger blocker) reduced the slow DC potential dose-dependently. These results suggest that the slow DC potential is mediated by forward mode operation of Na+/Ca2+ exchangers in non-neuronal cells, and that reactivation of Na+, K+-ATPase is necessary to the Na+/Ca2 +exchanger activity.     

Developmental exposure to lead causes inherent changes on voltage-gated sodium channels in rat hippocampal CA1 neurons

In this study, the effects of chronic lead (Pb(2+)) exposure, during day 0 of gestation (E0) to postnatal day 15 (P15), on voltage-gated sodium channel currents (I(Na)) were investigated in CA1 field of the hippocampus (CA1) neurons using the conventional whole-cell patch-clamp technique on rat hippocampal slices. We found that developmental lead exposure increased the activation threshold and the voltage at which the maximum I(Na) current was evoked, caused positive shifts of I(Na) steady-state activation curve, and enlarged I(Na) tail-currents; Pb(2+) delayed the activation of I(Na) in a voltage-dependent manner, prolonged the time course of the fast inactivation of sodium channels; Pb(2+) induced a right shift of the steady-state inactivation curve, accelerated the activity-dependent attenuation of I(Na), but made no significant effects on the time course of the recovery of I(Na) from inactivation and the fraction of inactivated channels. In addition, the co-treatment with alpha-tocopherol (VE), an effective antioxidant and free radical scavenger, completely prevented the aforementioned changes on I(Na). The alterations on I(Na) properties induced by developmental lead exposure were partly different from that in previous acute experiments under the conditions closer to physiological situation, and the process was considered related to the participating of lead in lipid peroxidation reaction, which has been reported to change the conformation and biophysical functions of membrane proteins.     

Rapid and slow swelling during hypoxia in the CA1 region of rat hippocampal slices.

The role of swelling in hypoxic/ischemic neuronal injury is incompletely understood. We investigated the extent and time course of cell swelling during hypoxia, and recovery of cell volume during reoxygenation, in the CA1 region of rat hippocampal slices in vitro. Cell swelling was measured optically and compared with simultaneous measurements of the extracellular DC potential, extracellular [K+], and synaptic transmission in the presence and absence of hypoxic depolarization. Hypoxia-induced swelling consisted of rapid and/or slow components. Rapid swelling was observed frequently and always occurred simultaneously with hypoxic depolarization. Additionally, rapid swelling was followed by a prolonged phase of swelling that was approximately 15 times slower. Less frequently, slow swelling occurred independently, without either hypoxic depolarization or a preceding rapid swelling. For slices initially swelling rapidly, recovery of both cell volume and the slope of field excitatory postsynaptic potentials were best correlated with the duration of hypoxia (r = 0.77 and 0.87, respectively). This was also the case for slices initially swelling slowly (r = 0.70 and 0.58, respectively). In contrast, the degree of recovery of cell volume was the same at 30 or 60 min of reoxygenation, indicating that prolonging the duration of reoxygenation within these limits was ineffective in improving recovery. Spectral measurements indicated that the hypoxia-induced changes in light transmittance were related to changes in cell volume and not changes in the oxidation state of mitochondrial cytochromes. The persistent impairment of synaptic transmission in slices swelling slowly (i.e., without hypoxic depolarization) indicates that swelling may play a role in this injury and that hypoxic depolarization is not required. Additionally, the correlation between the degree of recovery of cell volume and the degree of recovery of synaptic transmission during reoxygenation supports a role for swelling in hypoxic neuronal injury.     

Entorhinal projections to the hippocampal CA1 region in the rat: an underestimated pathway

The projections of the entorhinal cortex to CA1 in relation to the entorhinal-dentate projections were studied in the rat, using the anterograde transport of Phaseolus vulgaris leucoagglutinin. It was observed that the entorhinal cortex is heterogeneous with respect to the origin of these projections. Caudomedial portions of the entorhinal cortex mainly distribute fibers to the fascia dentata, whereas only a minor projection reaches CA1. Progressively more rostral and lateral parts of the entorhinal cortex project more strongly to CA1, at the expense of the number of fibers that terminate in the fascia dentata. The rostrolateral part of the entorhinal cortex, adjacent to the olfactory cortex and the amygdaloid complex, projects only to CA1.     

Effects of applied electric fields on low-calcium epileptiform activity in the CA1 region of rat hippocampal slices

It is well established that exogenous electric fields can suppress activity obtained in different models of epileptiform discharge such as penicillin and high potassium. In the low-calcium model of epilepsy, spontaneous epileptiform bursting is generated in the absence of synaptic transmission. It has been suggested that ephaptic interactions play a critical role in neuronal synchronization and burst propagation in this nonsynaptic model. We, therefore, tested the hypothesis that low-calcium bursting induced in the CA1 region of transverse and longitudinal hippocampal slices should be highly sensitive to exogenous electric fields. Uniform, low amplitude DC electric fields were applied during spontaneous low-calcium epileptiform activity. Modulation and full suppression of epileptiform activity was observed at field strengths between 1 and 5 mV/mm, a value significantly lower than in other in vitro models of epilepsy. We further investigated the hypothesis that the efficacy of electrical fields was related to changes in the extracellular space. Our results suggest that the osmolality of the perfusate can modulate the efficacy of electric fields. It was also observed that the ability of a field to suppress or modulate low-calcium activity was highly dependent on its orientation, polarity, as well as magnitude. Finally, it was observed that the extracellular potassium "waves" that normally accompany individual epileptiform events was abolished when the individual events were suppressed. These results suggest that DC fields modulate and suppress low-calcium activity by directly polarizing CA1 pyramidal cells.     

脑缺血预处理诱导海马CA1区神经元Bad磷酸化及其蛋白表达的变化

目的: 观察大鼠脑缺血预处理(CIP)后不同时间点海马CA1区胞质及线粒体中Bcl-xl/Bcl-2相关死亡促进因子(Bad)和p-Bad蛋白水平变化,探讨其在缺血耐受机制中的作用.方法: 采用SD大鼠4动脉结扎全脑缺血模型,利用焦油紫染色、免疫印迹法检测神经元的损伤及蛋白表达.结果: 焦油紫染色显示,脑缺血再灌注(I/R)3d,CA1区神经元大量损伤,与I/R组相比,CIP组CA1区存活的神经元增加;免疫印迹结果显示,CIP组胞质中Bad磷酸化水平于再灌注3h和3d出现高峰,而其蛋白表达无明显变化;与I/R对应时间点相比,CIP后再灌注3h和3d p-Bad升高.CIP后线粒体中p-Bad在再灌注不同时间点无明显变化,而其蛋白表达在再灌注后期(6h～3d)逐渐下降.结论: 脑缺血预处理可有效减轻海马CA1区神经元损伤;同时诱导神经元胞质中p-Bad蛋白水平升高,线粒体Bad蛋白表达降低.脑缺血预处理后Bad线粒体转位的降低可能是缺血耐受的重要机制.     

Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region

An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3–5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7–10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo . During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.     

Oxidant-mediated cAMP response element binding protein activation: calcium regulation and role in apoptosis of lung epithelial cells

Oxidant stress-mediated regulation of extracellular signal-regulated kinases (ERK1/2) is linked to pathologic outcomes in lung epithelium, yet a role for Ca2+ and Ca2+/cAMP-response element binding protein (CREB) in ERK1/2 signaling has not been defined. In this study, we tested the hypotheses that oxidants induce Ca2+-mediated phosphorylation of ERK and CREB, and that CREB is required for oxidant-induced proliferation and apoptosis. H2O2 initiated an influx of extracellular Ca2+ that was required for phosphorylation of both ERK and CREB in C10 lung epithelial cells. H2O2-mediated CREB phosphorylation was sensitive to MEK inhibition, suggesting that crosstalk between Ca2+, ERK, and CREB signaling pathways contributes to the oxidant-induced response. Reduction of CREB activity, using a dominant-negative CREB construct, inhibited c-fos steady-state mRNA levels, but unexpectedly enhanced bcl-2 steady-state mRNA levels after H2O2 exposure. Whereas inhibition of CREB activity had no detectable effect on H2O2 stimulation of cell cycle, loss of CREB activity significantly reduced the number of cells undergoing apoptosis. These data support a novel communication between Ca2+-ERK1/2 and CREB elicited by H2O2, and further provide evidence that CREB is an important regulator of apoptosis in oxidant-mediated responses of lung epithelial cells.     

高脂膳食和跑台运动构建模型大鼠腓肠肌葡萄糖转运体4和cAMP反应元件结合蛋白的变化

BACKGROUND: Some studies indicate that PI3K/Akt signaling pathway is associated with the expression of glucose transporter 4 (GLUT4) and the function of cAMP response element binding protein (CREB) in skeletal muscle. However, it is still unclear whether PI3K/Akt signaling pathway has the effects on CREB and GLUT4 in skeletal muscle of the rats with high-fat diet and treadmill exercise. OBJECTIVE: To investigate whether PI3K/Akt signaling pathway has the effects on CREB and GLUT4 in gastrocnemius muscle of the rats with high-fat diet and treadmill exercise.  METHODS: A total of 70 rats were fed with normal diet for 2 weeks, and randomly divided into common feed group (n=20) and high-fat feed group (n=50). Rats in both groups were respectively fed with common feed and high-fat feed for 8 weeks. The rats in the common feed group were equally assigned to common feed quiet group and common feed exercise group. 20 rats from the high-fat feed group whose body weight was 1.4 times of common rats were randomly and equally assigned to obese quiet group and obese exercise group. Rats in the quiet groups did not do exercises. Rats in the exercise groups received adaptive sports for 1 week and medium-intensity treadmill exercise for 8 weeks.  RESULTS AND CONCLUSION: (1) Impairments of PI3K/Akt signaling pathway appeared in obese rats, however, the quantity of GLUT4 expression did not change obviously in gastrocnemius muscles of obese rats. The reasons for the decrease of the nuclear protein CREB level of gastrocnemius muscles of obese rats might be related to the decrease of pAkt-Ser473 level. (2) The increase of the quantity of GLUT4 expression was accompanied by significantly up-regulated pAkt-Ser473 level by exercise intervention in gastrocnemius muscles of obese rats. Exercise intervention significantly increased the expression of nuclear protein CREB in gastrocnemius muscles of chow-fed rats and obese rats, which was consistent with the changes of pAkt-Ser473. These findings suggest that pAkt-Ser473 can play an important role in the effects of high-fat diet and exercise intervention on GLUT4 and CREB protein expression in gastrocnemius muscles of obese rats.       

慢性低压低氧暴露对小鼠海马CA1区神经元树突棘形态及细丝蛋白A表达的影响

目的:探讨低压低氧暴露对小鼠海马CA1区神经元树突棘形态及细丝蛋白A表达的影响。方法:6～8周龄C57BL/6雄性小鼠分为常氧暴露7 d组、常氧暴露14 d组、低压低氧暴露7 d组和低压低氧暴露14 d组。低压低氧暴露组置于低压舱模拟6 000 m海拔高原进行低压低氧暴露。Golgi染色法观察小鼠海马CA1区树突的分支数,以及基树突棘和顶树突棘长度和密度的变化; Western blot方法检测小鼠海马细丝蛋白A表达水平的变化;免疫组织荧光染色法检测小鼠海马CA1区细丝蛋白A的表达及分布变化。结果:与常氧暴露组相比,低压低氧暴露后,小鼠海马CA1区树突分支数的差异无统计学显著性,但基树突棘和顶树突棘的长度显著增加(P 0. 05),密度显著降低(P 0. 01)。低压低氧暴露后,小鼠海马细丝蛋白A表达水平低于常氧暴露组(P 0. 01或P0. 05)。免疫组织荧光染色显示细丝蛋白A在小鼠海马CA1区表达,低压低氧暴露后,海马CA1区细丝蛋白A表达水平降低(P 0. 05)。结论:慢性低压低氧暴露可影响小鼠海马CA1区细丝蛋白A表达,并导致海马CA1区神经元树突棘形态发生改变。     

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin suppresses contextual fear conditioning-accompanied activation of cyclic AMP response element-binding protein in the hippocampal CA1 region of male rats

We investigated the effect of in utero and lactational exposures to dioxin on adult offspring with contextual fear conditioning, a sex- and hippocampus-dependent learning paradigm; and we measured the conditioning-accompanied activation of cyclic AMP response element-binding protein (CREB) in the hippocampal CA1 region. Pregnant rats were treated with a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15. TCDD treatment decreased freezing time in conditioning tests of adult male offspring but not of female offspring. A similar, male-specific decrease was observed in the percentage of phosphorylated CREB-immunoreactive neurons in the CA1 region following conditioning in TCDD-treated rats. These results suggest that perinatal TCDD exposure impairs hippocampus-dependent learning in male offspring by suppressing CREB activation.     

Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death

Summary The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutanously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.     

穹窿海马伞切断鼠脑突触素动态变化及Morris水迷宫重复训练对其影响

目的在Morris水迷宫(MWM)重复训练的过程中观察穹窿海马伞切断大鼠的突触素(SYN)动态变化探讨阿尔茨海默病(AD)的发病机制和MWM重复训练学习和记忆能力对AD的影响,为临床应用提供实验依据。方法采用wistar大鼠60只,随机分为对照组、模型组和实验组,建模后连续四周给予Morris水迷宫重复训练定位航行和探索训练,分别评定大鼠空间学习和记忆能力,后进行海马突触素(SYN)免疫组化染色和超微电镜观察并进行统计学处理。结果随着训练次数的增加,对照组、模型组、实验组逃逸时间均逐渐缩短,实验组短于模型组,长于对照组(P0.05),提示空间学习能力得到提高。对照组、模型组和实验组大鼠在靶象限活动时间(s)百分比无明显差异(P0.05),提示空间记忆能力无明显提高。SYN免疫组化实验组SYN表达高于模型组,弱于对照组。结论MWM重复训练增加海马SYN表达可能与提高穹窿海马伞切断大鼠空间学习能力有关。     

Protein disulfide isomerase immunoreactivity and protein level changes in neurons and astrocytes in the gerbil hippocampal CA1 region following transient ischemia

We investigated the temporal and spatial alterations of protein disulfide isomerase (PDI) immunoreactivity and protein level in the hippocampus proper after 5 min transient forebrain ischemia in gerbils. PDI immunoreactivity was significantly altered in the hippocampal CA1 region. PDI immunoreactivity in the sham-operated animals was found in non-pyramidal cells. At 30 min after ischemia, PDI immunoreactivity was shown in the pyramidal cells of the stratum pyramidale (SP): the PDI immunoreactivity in the pyramidal cells was increased up to 12 h after ischemia. Thereafter PDI immunoreactivity was decreased, and the PDI immunoreactivity was shown in non-pyramidal cells 2 days after ischemia. Four to 5 days after ischemia, almost pyramidal cells in the CA1 region were lost because the delayed neuronal death occurred. At this time period, PDI immunoreactivity was expressed in some astrocytes as well as some neurons. The results of the Western blot analysis were consistent with the immunohistochemical data. These findings suggest that increase of PDI in pyramidal cells may play a critical role in resistance to ischemic damage at early time after ischemic insult, and that expression of this protein in astrocytes at late time after ischemic insult is partly implicated in the acquisition of tolerance against ischemic stress.     

Sevoflurane immediate preconditioning alters hypoxic membrane potential changes in rat hippocampal slices and improves recovery of CA1 pyramidal cells after hypoxia and global cerebral ischemia

Pretreatment with anesthetics before but not during hypoxia or ischemia can improve neuronal recovery after the insult. Sevoflurane, a volatile anesthetic agent, improved neuronal recovery subsequent to 10 min of global cerebral ischemia when it was present for 1 h before the ischemia. The mean number of intact hippocampal cornus ammonis 1 (CA1) pyramidal neurons in rats subjected to cerebral ischemia without any pretreatment was 17+/-5 (neurons/mm+/-S.D.) 6 weeks after the ischemia; na?ve, non-ischemic rats had 177+/-5 neurons/mm. Rats pretreated with either 2% or 4% sevoflurane had 112+/-57 or 150+/-15 CA1 pyramidal neurons/mm respectively (P<0.01) 6 weeks after global cerebral ischemia. In order to examine the mechanisms of protection we used hypoxia to generate energy deprivation. Intracellular recordings were made from CA1 pyramidal neurons in rat hippocampal slices; the recovery of resting and action potentials after hypoxia was used as an indicator of neuronal survival. Pretreatment with 4% sevoflurane for 15 min improved neuronal recovery 1 h after the hypoxia; 90% of the sevoflurane-pretreated neurons recovered while none (0%) of the untreated neurons recovered. Pretreatment with sevoflurane enhanced the hypoxic hyperpolarization(-6.4+/-0.6 vs. -3.3+/-0.3 mV) and reduced the final level of the hypoxic depolarization (-39+/-6 vs. -0.3+/-2 mV) during hypoxia. Chelerythrine (5 muM), a protein kinase C/protein kinase M inhibitor, blocked both the improved recovery (10%) and the electrophysiological changes with 4% sevoflurane preconditioning. Two percent sevoflurane for 15 min before hypoxia did not improve recovery (0% recovery both groups) and did not enhance the hypoxic hyperpolarization or reduce the final depolarization during hypoxia. However if 2% sevoflurane was present for 1 h before the hypoxia then there was significantly improved recovery, enhanced hypoxic hyperpolarization, and reduced final depolarization. Thus we conclude that sevoflurane preconditioning improves recovery in both in vivo and in vitro models of energy deprivation and that preconditioning enhances the hypoxic hyperpolarization and reduces the hypoxic depolarization. Anesthetic preconditioning may protect neurons from ischemia by altering the electrophysiological changes a neuron undergoes during energy deprivation.     

In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: relationship to performance on the Morris water maze.

Young and aged Fischer 344 rats were tested on the place and cue versions of the Morris water maze task. Although all of the young animals reached criterion within the 8-day testing period, the aged animals could be divided into two groups on the basis of their performance to criterion: achievers and nonachievers. Upon completion of the water maze testing, the animals were sacrificed, and their brains were processed for in vitro autoradiography of hippocampal excitatory amino acid receptors. Significant differences were found between the young and old rats in the levels of N-methyl-D-aspartate, CPP, kainate, and AMPA binding in subregions of the hippocampus. Despite the age-related decline in hippocampal glutamate receptors, no relationship was observed between the density or distribution of excitatory amino acid receptors and performance on the water maze task in the aged rats.