Biochemical evidence for enhanced sensitivity to N-methyl-d-aspartate in the hippocampal formation of kindled rats

The inhibitory effect of N-methyl-d-aspartate (NMDA) upon carbachol-stimulated phosphoinositide (PI) hydrolysis was studied in transverse hippocampal slices prepared from control and amygdaloid kindled rats. Kindling significantly increased the inhibitory effect of NMDA (10 μM) in slices prepared from animals 24 h after the last class 5 kindled seizure, resulting in a steepening of the dose-response curve for NMDA. The enhanced sensitivity to NMDA was long-lasting in that it was also present in slices prepared from animals sacrificed 28–35 days after the last class 5 seizure. The increased sensitivity to NMDA was selective in that inhibition of carbachol-stimulated PI hydrolysis by kainic acid or phorbol-12,13-diacetate was not different in control and kindled animals. Neither NMDA, kainic acid, phorbol ester nor carbachol alone had any significantly differents effects in slices from kindled versus control animals. These data demonstrate a selective and enhanced sensitivity of the kindled hippocampus to NMDA. This enhanced sensitivity to the principal class of excitatory neurotransmitter may be one mechanism underlying the development and maintenance of kindled epilepsy.     

Dorsal-ventral gradient in vulnerability of CA1 hippocampus to ischemia: a combined histological and electrophysiological study

Transverse hippocampal slices were prepared after 7 days survival from rats subjected to 8 min of global incomplete ischemia by temporary occlusion of both carotid arteries and hypotension. The slices demonstrated a dorsal-ventral gradient in the amount of ischemic neuronal necrosis in the CA1 region. Histologically ischemic cell change decreased from 90% dorsoseptally to 10% ventrotemporally. Electrophysiological analysis of the number of slices with viable synaptic transmission in CA1 also revealed a septotemporal gradient in susceptibility to ischemia.     

Interaction of age and sex in sympathetic axon ingrowth into the hippocampus following septal afferent damage

Summary Damage to the medial septal nucleus or to the fimbria/fornix in the adult rat elicits sprouting of vascular sympathetic fibers into the deafferented regions of the hippocampal formation. The following study examines the effects of developmental stage and sex on this sprouting phenomenon using both fluorescence histochemistry and high affinity uptake of noradrenaline. We find that (1) the sprouting, which is reduced in adult and juvenile males relative to females, is equivalent in the two sexes after transections at postnatal day 3, and (2) the period of maximum ingrowth is sexually regulated, occurring near postnatal day 3 in the male and postnatal day 13 in the female.     

Golgi study on cat hippocampal formation

Summary The Golgi architecture of the Fascia dentata and hippocampus is described in the cat. The main cell types are like those found in other species. The initial collaterals of granule cell axons were demonstrated and are commented on. The interneurons proved to be of several types and subtypes not observed in lower species. The intrinsic fibers and few of the afferents — both in the dentate fascia and in the hippocampus — are discussed.     

Exploratory behaviour in two selectively-bred lines of mice after intrahippocampal injection of methylscopolamine

The temporal course of exploratory behaviour in male mice from two selected lines SRH (showing frequent rearing responses) and SRL (with less frequent rearing), following injection of methylscopolamine into the hippocampus was studied. The anticholinergic drug decreased exploration in the SRH line and prolonged it in the SRL line. The experiment supplies further proof that a cholinergic system in this brain area regulates responses to novelty and that this system is controlled by genetic factors.     

The role of the hippocampal-nucleus accumbens pathway in radial-arm maze performance

The role of the glutamatergic hippocampal-nucleus accumbens pathway in relaying hippocampal information via the nucleus accumbens to the motor system was investigated behaviorally using the radial-arm maze paradigm in rats. Bilateral injections of kynurenic acid, a glutamate antagonist, into the nucleus accumbens increased the latency to initiate movement during performance of an 8-arm radial maze with all arms baited and with 4 arms baited. Injections of kynurenic acid did not change the number of visits to previously visited arms (i.e. working memory errors) on both versions of the 8-arm radial maze. However, on the 8-arm radial maze with 4 arms baited, injections increased the number of visits to unbaited arms (i.e. reference memory errors). Similar injections were made in rats with ibotenic acid lesions of the prefrontal cortex in order to eliminate the glutamatergic prefrontal cortex-nucleus accumbens pathway so as to investigate the glutamatergic hippocampal-nucleus accumbens pathway. These rats displayed similar deficits on the radial-arm maze as non-lesioned rats (i.e. enhanced latency to initiate movement and reference memory errors). These findings suggest that the glutamatergic hippocampal-accumbens pathway plays a role in radial-arm maze performance by transferring information required for performing a radial-arm maze to the motor system.     

Toxicity of L-proline toward rat hippocampal neurons

Intrahippocampal injections of L-proline, a neutral amino acid excitant, nonselectively destroyed pyramidal and granule cells. Co-administration of equimolar kynurenate, an excitatory amino acid antagonist, markedly reduced the extent of neuronal cell death. L-Proline destroyed far more hippocampal neurons than D-proline, in keeping with its greater neuroexcitatory potency. L-Proline must therefore be added to the list of excitotoxins present in brain. Its excitotoxic action may be related to the neurological and cognitive deficits associated with hyperprolinemia.     

Experience aids recovery of spontaneous alternation following hippocampal damage

Lesions of the dorsal hippocampus of rats significantly impaired spontaneous alternation behavior measured 14 days after surgery. However, following repeated testing over a three day period, these animals recovered normal spontaneous alternation levels, not significantly different from performance of sham controls. Hippocampal operates that received only nonspecific experience in a runway were significantly impaired when tested in spontaneous alternation. Possible recovery mechanisms are discussed.     

大鼠全脑缺血与再灌流对大脑皮层和海马形态结构的影响

采用闭塞大鼠四条动脉的全脑缺血模型，用光镜观察缺血３０ｍｉｎ及再灌流不同时期大脑皮层和海马形态结构的改变，结果显示：①病变主要表现为神经细胞变性、坏死和胶质细胞增生；②病变主要发生在缺血后的再灌期，在再灌后的７２小时，病变显著和出现各种特征性改变，③在海马见到的病变要比大脑皮层明显、深刻得多，海马是缺血性脑损伤的最易感区。     

No enhancement by nitric oxide of glutamate release from P2 and P3 synaptosomes of rat hippocampus

Effects of nitric oxide on glutamate (Glu) release in long-term potentiation (LTP) were investigated by superfusion of conventional (P2) and large (P3) synaptosomes prepared from the rat hippocampus. Basal releasing rates of endogenous Glu from P2 and P3 fractions were 103.6 and 85.2 pmol/min/mg protein, respectively. Exposure to a depolarizing concentration of KCl (30 mM) evoked 3.58- and 4.52-fold increases in releasing rates of Glu from P2 and P3 fractions, respectively. Although the perfusion with sodium nitroprusside (NP, 10⁻³ M), a nitric oxide-releasing agent, failed to augment the K⁺-evoked releases of Glu from P2 and P3 synaptosomes, NP enhanced that from slices of the hippocampus by 39% without changing basal release. Similarly, 8-bromoguanosine3′ : 5′-cyclic monophosphate (10⁻⁴ M) increased the K⁺-evoked release of Glu from slices by 30%, but not from either synaptosomes. When synaptosomes were prepared from the hippocampus which was pretreated with two trains of electrical field stimulation (100 Hz, 0.1 ms, for 2 s), K⁺-evoked releases of Glu from P2 and P3 synaptosomes were increased by 15% and 23%, respectively. Although nitric oxide is postulated to function as a retrograde messenger to maintain LTP, present results suggest that nitric oxide may not directly act upon nerve terminals to enhance glutamate release, but that interventions of glias and short neurons may be involved in the presynaptic mechanism of LTP.