Double evoked responses to the electrical stimulation of Shaffer's collaterals in CA1 hippocampal field

Double evoked responses to single current pulses applied to Shaffer's collaterals were observed in CAI hippocampal field in freely moving rats. The second response was an irregular population EPSP with constant latency sometimes accompanied by a population spike. The effect was observed in 22 of 54 tested rats (40.74%). In 10 of these 22 animals (45.45%) the second response was evoked by a weak testing stimulus of at least of a single collateral, in the remaining 12 rats the second response appeared to stimulation with increased current or after potentiation of the stimulated pathways. The second responses were very sensitive to the functional state of an animal and were recorded at the state of rest or during sleep. The latencies of the second response measured from the beginning of the first response were very close in different animals and with low intraindividual variability indicating that the same circuits are involved in its generation. It is suggested that hippocampus can support dynamic processes such as reverberation of signals.     

The effect of forelimb deafferentation in early postnatal ontogeny on the development of synaptic transmission in the hippocampus]

Hippocampal slices from 15-20-day-old Wistar rats were used to study the development of some features of synaptic transmission in hippocampus and the influence of partial limitation of the sensory inflow in the early ontogeny of this transmission. The dynamics of population spike changes was observed in the CA1 hippocampal field in response to stimulation of Schaffer collaterals. The early ontogenetic limitation of the sensory inflow was accomplished by cutting n. medianus on the 13th day. Between the 15th and 20th days, the dynamics of the population spike amplitude increase in the control and experimental animals was similar, however, the response amplitude of the control rats remained higher than in the experimental animals throughout the whole period of observation. It is suggested that the partial limitation of sensory inflow from a forelimb at the early stages of the ontogeny alters the formation of synaptic transmission in hippocampus.     

慢性吗啡给予、戒断及再给药过程中大鼠海马感觉门控的动态变化

药物成瘾被认为是药物长期作用于脑而产生的一种慢性复吸性脑疾病,长期反复的药物（如吗啡）滥用会导致一系列严重后果,如药物依赖、药物耐受、强迫性药物寻求等。本实验利用条件化位置偏好（conditioned place preference,CPP）模型来检测大鼠对吗啡依赖和心理渴求等过程;采用双声刺激听觉诱发电位来研究大鼠在慢性吗啡给予、戒断以及再给药过程中海马感觉门控（N40）的动态变化。吗啡组大鼠注射吗啡（10mg／kg,i．p．）12d,经历第一次戒断12d,再次注射吗啡（2．5mg／kg,i．P．）1d,之后经历第二次戒断2d;对照组大鼠注射同体积生理盐水,其余实验条件与吗啡组相同。CPP实验表明,这种药物给予方法促使大鼠对吗啡产生药物依赖和心理渴求。双声刺激诱发电位实验表明,吗啡组大鼠在吗啡给予期间海马感觉门控受到损伤;第一次戒断期的第1～2天海马感觉门控能力减弱,第3天增强,第4～12天逐渐恢复到正常水平;再次给予吗啡后海马感觉门控能力与对照组相比显著降低,并且随后2d的戒断期内海马感觉门控能力也一直保持较低水平,表明再次给药使大鼠海马感觉门控对吗啡更加敏感化。结果提示,长期反复的吗啡给予及再给药干扰了海马的感觉门控能力,吗啡成瘾对大脑可能产生长期影响。     

Effect of isatin on the electrical activity in the rat hippocampus cells

In vitro superfusion of rat hippocampal slices with isatin changed the population spikes. Isatin perfusion produced two clear effects. 50 microM isatin it increased the amplitude of the population spike in the CA1 evoked by stimulation of stratum radiatum. This effect was readily reversible. 100 microM isatin decreased the population spike amplitude with minimal effect on its latency. High initial response were more suppressed. This effect on the population spike amplitude was not eliminated even after 1 h of washing with saline. The data obtained suggest that isatin-induced electrophysiological changes are involved into the anticonvulsant effect of isatin.     

Neuronal transmission of hippocampal CA1 neurones is modulated by corticotropin-like intermediate lobe peptide [CLIP; ACTH(18–39)]

The study was conducted to test whether CLIP [ACTH(18–39)] influences the neuronal transmission and the induction of longterm potentiation (LTP) in the hippocampus. The population spike was recorded in the hippocampal CA1 region of freely moving rats before and after intracerebroventricular (ICV) administration of CLIP in comparison to ACTH and saline (controls). After infusion of CLIP, the population spike amplitude (PSA) rose to about 200% of baseline values. After reaching this level, it was impossible to induce a further increase of PSA by tetanization. However, if the stimulus intensity was reduced to a new baseline level, electrically induced LTP could be observed. There were no significant changes after infusion of ACTH. Our results indicate that the ICV administration of CLIP leads to an enhancement of excitability in the hippocampal CA1 region, which might be independent of LTP.     

Kindling during early postnatal development: the effects on the maturation of the hippocampal electrophysiological characteristics

The effect of repeated pentylentetrazole (PTZ) administration on the postnatal development of hippocampal electrophysiological indices has been studied. Contrary to adult rats, repeated PTZ injections did not intensify convulsive activity in rat pups (from postnatal day 14). We did not observe any between-group differences in population spike amplitudes and paired pulse facilitation (PPF) ratio at 70 ms interpulse interval during early period of postnatal development, PPF suppression at short interlulse interval (15 ms) only was significantly less in PTZ group as compared with saline-injected controls, but the effect of saline injections has developed in the same directio However PTZ resulted in the modification of developmental profile. Besides the change of paired-pulse inhibition (15 ms), in the slices of young rats (27-48 postnatal days) the input-output curve was specifically modified and the intensity-dependent increase in population spike amplitudes was less expressed than in the slices of young control rats repeatedly subjected to saline injection, while PPF ratio of both groups was significantly decreased in a similar way, as compared with passive controls. In addition, LTP magnitude in the slices of PTZ group was also suppressed. These modifications did not correlate with convulsive activity. A significant correlation with convulsive activity was found only for population spike amplitudes evoked by low, near-threshold stimuli.     

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…     

Changes in [3H]Nitrendipine Binding and γ-Aminobutyric Acid Release in Rat Hippocampus Following Repeated Morphine Administration

An antagonistic effect of calcium on the action of morphine was studied in rat hippocampal slices. The effect of repeated administration of morphine on gamma-aminobutyric acid (GABA) release and binding of [3H]nitrendipine, a calcium antagonist, was also examined. (1) In rat brain hippocampal slices, morphine enlarged the amplitude of the field potentials evoked in pyramidal neurons, disinhibiting them through basket cells. When the calcium concentration was elevated, potentiation of the field potentials by morphine was reduced. Decrease of the calcium concentration, on the other hand, enhanced the potentiating effect of morphine. Following repeated administration of morphine, its enhancing effect on the field potentials in slices was not observed. (2) In hippocampal membrane fractions obtained from rats repeatedly treated with morphine, enhancement of [3H]nitrendipine binding was observed. (3) In hippocampal slice preparations from rats receiving morphine repeatedly, K+ (45 mM)-stimulated [3H]GABA efflux was enhanced. The above results indicate that morphine antagonizes calcium, thereby reducing the release of transmitters. Furthermore, increase in calcium channels following repeated treatment of rats with morphine may explain the mechanism underlying development of tolerance.     

Opioid pharmacology in the rat hippocampal slice

The ability of several opioids in potentiating the synaptic activation of CA1 pyramidal cells in the rat hippocampal slice were compared. Morphine and the opioid peptides, (D-ala2, D-leu5)-enkephalin (DADL), morphiceptin, beta-endorphin, and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSThr) caused a concentration-dependent, naloxone-reversible shift to the left in the input-output (IO) curve constructed by plotting the population spike as a function of the field EPSP. These opioids then produced an increase in the size of the population spike while leaving the EPSP unaffected. In contrast, the kappa agonist prototype, ethylketazocine, had no effect on the IO curve when perfused in concentrations up to 10 microM. The rank order of potency for the opioids in the CA1 region of the hippocampus was DADL greater than DSThr greater than beta-endorphin greater than morphiceptin greater than morphine much greater than ethylketazocine. Thus, opioids that are more specific for delta opiate receptors were the most potent and mu receptor agonists, the least potent in this action. Taken together with previous studies suggesting that morphine and DADL may interact with a common opiate receptor in the CA1 region, the results are consistent with the notion that these epileptiform effects may be primarily mediated by delta opiate receptors in this area although the potency of morphiceptin indicates that mu receptors play some role in this effect.     

Sensitization to the hyperthermic and catecholamine-releasing effects of morphine

Rats were given alternating injections (one per day) of morphine (5 mg/kg) and saline, each substance paired with a distinct set of environmental cues. Over the course of nine injections of the drug, the hyperthermic response to morphine gradually increased. On the tenth such exposure to morphine, half of the rats were injected in the presence of cues previously paired with the drug, and half were injected in the presence of saline cues. In the former (drug-cue) group, hyperthermia, and plasma norepinephrine and epinephrine levels were significantly greater than in rats receiving morphine for the first time. The latter (saline-cue) group showed an intermediate thermic and catecholamine response, not statistically different from drug-cue or control animals. Under these conditions, the enhanced hyperthermic response to morphine (which has been variously described as sensitization or tolerance), was found to be accompanied by a similar increase in elevation of plasma catecholamines.     

NMDA-induced stimulation of glycolysis in developing hippocampal cell cultures

Developmental changes in energy metabolism of primary hippocampal cell cultures from newborn rats were investigated during the first 3 weeks. These changes were measured by intensity of and number of cells exhibiting NAD(P)H fluorescence in response to NMDA-induced activation of neuronal activity. We observed gradual changes of stimulation-evoked NAD(P)H signaling over the first 3 weeks, such that at day 7 and 16, this stimulation is minimal, while at 5 and 12 days, it is maximal. These results describe a biphasic pattern that was similar to earlier findings from experiments investigating developmental changes in population spike amplitudes or glutamate release in young rats. Inhibition of mitochondrial respiration by KCN revealed that the NMDA-evoked stimulation of energy metabolism is mainly due to increased glycolytic activity.     

Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior.

The development of a secondary reinforcer as a result of associating a neutral stimulus (buzzer) with intravenous (IV) doses of morpine was studied in rats. Secondary reinforcement developed in the absence of physical dependence and followed the association of the stimulus with either response-contingent or non-contingent injections of morphine. Strength of the conditioned reinforcer, measured in terms of responding on a lever for the stimulus plus infusion of saline solution, was proportional to the unit dosage of morphine employed in pairings of buzzer and drug. When extinction of the lever-press response for IV morphine was conducted (by substituting saline for morphine solution) in the absence of the conditioned reinforcing stimulus, it was seen later that the stimulus could still elicit lever responses, until it too had been present for a sufficient interval of non-reinforced responding. Similarly, extinction of the response for morphine by blocking its action with naloxone in the absence of the stimulus did not eliminate the conditioned reinforcement. Another study showed that a passive, subcutaneous (SC) dose of morphine served to maintain lever-pressing on a contingency of buzzer plus saline infusion. Furthermore, the stimuli resulting from the presence of morphine (after a SC injection) were able to reinstate the lever-responding with only the buzzer-saline contingency when such responses had previously been extinguished. Moreover, it was shown that d-amphetamine could restore responding under the same conditions, and that morphine could also do so for rats in which the primary reinforcer had been d-amphetamine. It is suggested that animal data such as these show that procedures designed for the elimination of human drug-taking behavior must take into account secondary reinforcers as well as the primary reinforcer(s).     

Effects of adrenalectomy on in vitro evoked electrophysiological activity of the hippocampus in BALB/c mice

The physiological properties of hippocampal slices from intact or adrenalectomized (ADX) BALB/c mice were studied in vitro. Mouse hippocampal slices displayed features similar to those observed in other species in terms of postsynaptic characteristics of response to stratum radiatum stimulation. In adrenalectomized mouse, the amplitude of population spike was reduced whereas the latency of population spike and cell responses to paired stimuli volleys were unchanged. The role of the endocrine status in this modification is discussed.     

Verapamil counteracts the masking of long-lasting potentiation of hippocampal population spike produced by 2-amino-5-phosphonovalerate

In transversely sectioned rat hippocampal slices the effects of 2-amino-5-phosphonovalerate (APV), presumably a selective N-methyl-DL-aspartate antagonist, were examined on the development of long-lasting potentiation (LLP) of the CA1 population spike produced by Schaffer collateral tetanization (100 Hz, 1 s). APF (100 nA, 5 min), when applied 150-200 micron away from the CA1 cell bodies (apical dendritic area), had no significant effect if the population spike was evoked at 0.1 Hz, but produced a depression of the population spike if a 100 Hz tetanus was given during its iontophoresis. This depressant effect of APV was counteracted by verapamil (0.33 microM, 3 min) and LLP induced by the 100 Hz tetanus was unmasked. It is suggested that APV does not antagonize LLP, but only masks it by allowing CA++ influx into CA1 neurones that induces a depression. The results also raise doubts as to the selectivity of APV as an amino acid antagonist.     

Glucose Deprivation Results in a Lactate Preventable Increase in Adenosine and Depression of Synaptic Transmission in Rat Hippocampal Slices

Abstract: The effect of glucose deprivation on adenosine levels and on synaptic transmission was investigated in rat hippocampal slices. Incubation of hippocampal slices either in glucose-free medium or in the presence of the glucose transport inhibitor cytochalasin B (50 μ M ) increased bath adenosine levels and depressed the extracellularly recorded synaptic potential or population spike. The addition of lactate (10 m M ), a precursor for mitochondrial ATP generation, prevented the elevation in adenosine and the depression of the population spike. These results indicate that the neuroinhibitory modulator adenosine is elevated during glucose deprivation and contributes to the hypoglycemic depression of synaptic transmission. The increase in adenosine during glucose deprivation can be prevented by providing substrate for mitochondrial ATP generation. The present results indicate an interaction between lactate and adenosine such that an increase in lactate may contribute to a decline in adenosine production.     

Thermal dependence of neural activity in the hamster hippocampal slice preparation

1. Neural activity was recorded in an in vitro hamster hippocampal slice preparation while the temperature of the Ringer's solution bathing in the slice was controlled at selected levels. 2. The amplitude of the population spike (action potentials from a group of pyramidal cells) was measured as bath temperature was lowered from 35 degrees C to temperatures where a response could not be evoked. 3. Plots of population spike amplitude versus temperature have bell-shaped curves. The population spikes increased in amplitude as temperature was lowered from 35 degrees C, reached a peak amplitude between 25 and 20 degrees C, and then decreased until a response could not be evoked when temperature was further lowered. 4. These in vitro results obtained in the slice preparation are related to in vivo hippocampal studies. Results are interpreted as consistent with the proposal reviewed here that neural activity in the hippocampus plays a role at specific stages of entrance into and arousal from hibernation.     

Effect of thyrotropin-releasing hormone on rat myometrium

The effect of TRH in vitro was observed on electromyograms and isometric tension changes in the uterine horn isolated from the rat. TRH induced transient prolongation of the duration of spike bursts in the electromyogram and an increased tension in contraction of diestrous uterine horns. No distinct response to TRH was elicited in preparations from rats during other estrous stages. TRH produced a contraction associated with a burst of spike potentials in the quiescent horn from the estrogen-primed ovariectomized rat. Priming with progesterone was not a prerequisite for responsiveness to TRH. In a medium with a high Ca concentration, diestrous uteri were quiescent but a transient contraction associated with a burst of spike potentials was induced by TRH. In a Ca-free medium, TRH failed to elicit any response in the diestrous uterus but acetylcholine induced a contraction without associated spike potentials. It appears that TRH stimulates Ca-influx into the uterine muscle in which responsiveness is dependent on estrogen priming.     

Hippocampal desynchronization of functional connectivity prior to the onset of status epilepticus in pilocarpine-treated rats

Status epilepticus (SE), a pro-epileptogenic brain insult in rodent models of temporal lobe epilepsy, is successfully induced by pilocarpine in some, but not all, rats. This study aimed to identify characteristic alterations within the hippocampal neural network prior to the onset of SE. Sixteen microwire electrodes were implanted into the left hippocampus of male Sprague-Dawley rats. After a 7-day recovery period, animal behavior, hippocampal neuronal ensemble activities, and local field potentials (LFP) were recorded before and after an intra-peritoneal injection of pilocarpine (350 mg/kg). The single-neuron firing, population neuronal correlation, and coincident firing between neurons were compared between SE (n?=?9) and nonSE rats (n?=?12). A significant decrease in the strength of functional connectivity prior to the onset of SE, as measured by changes in coincident spike timing between pairs of hippocampal neurons, was exclusively found in SE rats. However, single-neuron firing and LFP profiles did not show a significant difference between SE and nonSE rats. These results suggest that desynchronization in the functional circuitry of the hippocampus, likely associated with a change in synaptic strength, may serve as an electrophysiological marker prior to SE in pilocarpine-treated rats.     

Distinct cellular immune responses following primary and secondary influenza virus challenge in cotton rats

To evaluate cell-mediated immunity in influenza-infected cotton rats, we compared the cellular composition of spleen, mediastinal lymph nodes (MLN) and bronchoalveolar lavage (BAL) after primary and secondary infection. There was an increase in cellularity in the MLN after primary infection that was further expanded upon rechallenge. CD4(+) T cells expanded after primary infection, but there was preferential increase in the number of CD4-negative T cells following secondary challenge. After primary infection, a large proportion of the monocytes and NK cells were present in the BAL while a T cell population dominated after secondary infection. CD4(+) T cells were predominant in this population unless the animals had been challenged with heterosubtypic influenza A virus. These studies are the first to show evidence of a memory T cell response to influenza infection in cotton rats and show quantitative and qualitative differences between the recall response to homosubtypic and heterosubtypic viruses.     

NGF,BDNF and Arc mRNA Expression in the Hippocampus of Rats After Administration of Morphine

Morphine can influence immediate early genes (IEG) of activity-regulated cytoskeletal-associated protein (Arc) and brain-derived neurotrophic factor (BDNF) which are activated in response to physiological stimuli during learning, as well as the nerve growth factor (NGF) gene which increases the expression of several IEGs for memory formation. The purpose of the current study was first to evaluate the effect of acute (1-day) and subchronic (15-days) morphine administration on memory retrieval of rats and second to determine the hippocampal expression of NGF, BDNF and Arc genes as potential contributors in the observed effects in each setting. The effects of morphine (intraperitoneal, 10, 15 and 20 mg/kg) on memory function and gene expression were assessed using inhibitory avoidance test and real-time polymerase chain reaction, respectively. We found that a single dose of morphine at the highest dose of 20 mg/kg decreases the post-training step-through-latency, while repeated administration of the same dose for 15 successive days increases this indicator of memory retrieval. We did not detect a significant change in the hippocampal expression of Arc, BDNF or NGF genes after a single episode of morphine treatment. However, subchronic morphine administration (15 and 20 mg/kg) increased the expression of Arc and BDNF genes in a dose dependent manner. A higher mRNA expression for the NGF was observed at the higher dose of 20 mg/kg. We hypothesize that the subchronic effects were morphine-induced behavioral sensitization which may have been enhanced through increased hippocampal Arc expression.