低氧大鼠海马脑片CA1区长时程增强的变化及ACTH的作用

目的: 研究ACTH对低氧海马脑片CA1区长时程增强的影响。方法: 细胞外记录海马脑片CA1区诱发的群峰电位(PS)和强直刺激诱发的长时程增强(LTP)。结果: 低氧(5% O₂+90% N₂+5% CO₂或11.2% O₂+83.8% N₂+5% CO₂)灌流海马脑片后, LTP的诱出时间显著延长、诱出率明显降低, PS迅速减少并逐渐消失。预先灌流ACTH可改善上述效应。结论: 低氧可损害海马脑片CA1区LTP的诱发过程, ACTH可使之改善。     

Depletion of ATP and release of presynaptic inhibition in the CA1 region of hippocampal slices during hypoglycemic hypoxia

Transient recovery (TR) of evoked synaptic potentials and ATP depletion during the late stage of hypoxic hypoglycemic insults were investigated in rat hippocampal slices. TR was observed not only in the late stage of insult, but also during recovery. The concentration of ATP corresponded to the appearance (27% of control) and disappearance (15% of control) of TR. Paired pulse studies showed the presynaptic nature of the release of inhibition of synaptic transmission during TR. Both N- and P/Q-type voltage-dependent calcium channels were involved in the appearance of TR. This evidence suggests that underlying mechanisms of TR appearance during hypoxic hypoglycemic insult might be related to ATP depletion and release of A1 adenosine receptor mediated inhibition of presynaptic voltage-dependent calcium channels.     

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.     

Nitric oxide inhibitors attenuate ischemic degeneration in the CA1 region of rat hippocampal slices

We examined the involvement of nitric oxide (NO) in ischemic brain damage using hippocampal slices prepared from 30 day old albino rats and exposed to 20 min of oxygen/glucose deprivation (ischemia) followed by 90 min postincubation in oxygen- and glucose-containing media. Damage in the CA1 region was rated on a 0 (intact) to 4 (severe neuronal damage) scale by a rater blind to the experimental condition. Control slices exposed to ischemia were rated as 2.8 ± 0.4 (N = 12). -N^G-Monomethylarginine (100 μM) and -N^G-nitroarginine (100 μm), non-selective NO synthase (NOS) inhibitors, diminished ischemic damage (0.6 ± 0.3, N = 8, and 1.0 ± 0.5, N = 4, respectively). An inhibitor of brain NOS, 7-nitroindazole (30 μM), was also effective against ischemic degeneration (0.7 ± 0.3, N = 5). These results suggest that activation of NOS is involved in ischemic degeneration in the CA1 region.     

Conditions sufficient for nonsynaptic epileptogenesis in the CA1 region of hippocampal slices.

Nonsynaptic mechanisms exert a powerful influence on seizure threshold. It is well-established that nonsynaptic epileptiform activity can be induced in hippocampal slices by reducing extracellular Ca(2+) concentration. We show here that nonsynaptic epileptiform activity can be readily induced in vitro in normal (2 mM) Ca(2+) levels. Those conditions sufficient for nonsynaptic epileptogenesis in the CA1 region were determined by pharmacologically mimicking the effects of Ca(2+) reduction in normal Ca(2+) levels. Increasing neuronal excitability, by removing extracellular Mg(2+) and increasing extracellular K(+) (6-15 mM), induced epileptiform activity that was suppressed by postsynaptic receptor antagonists [D-(-)-2-amino-5-phosphonopentanoic acid, picrotoxin, and 6,7-dinitroquinoxaline-2,3-dione] and was therefore synaptic in nature. Similarly, epileptiform activity induced when neuronal excitability was increased in the presence of K(Ca) antagonists (verruculogen, charybdotoxin, norepinephrine, tetraethylammonium salt, and Ba(2+)) was found to be synaptic in nature. Decreases in osmolarity also failed to induce nonsynaptic epileptiform activity in the CA1 region. However, increasing neuronal excitability (by removing extracellular Mg(2+) and increasing extracellular K(+)) in the presence of Cd(2+), a nonselective Ca(2+) channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity in vitro. Both novel models were characterized using intracellular and ion-selective electrodes. The results of this study suggest that reducing extracellular Ca(2+) facilitates bursting by increasing neuronal excitability and inhibiting Ca(2+) influx, which might, in turn, enhance a persistent sodium conductance. Furthermore, these data show that nonsynaptic mechanisms can contribute to epileptiform activity in normal Ca(2+) levels.     

Hyperexcitability of hippocampal CA1 region in brain slices after GABA withdrawal.

The interruption of GABA infusion in the cerebral cortex and in the hippocampus produces electrographic seizures in rats. Here, we have used the hippocampal slice preparation to induce a 'GABA withdrawal syndrome (GWS)'. With the stimulation parameters used (0.2 Hz, 200 microseconds), activation of the Schaffer afferents produced one population spike in the CA1 subfield, while multiple population spikes were observed in the slices previously incubated in GABA. Also, we recorded an increase in the amplitude of the population spike when compared to its control value. Paired pulse test showed absence of recurrent inhibition in these slices. These results suggest a dysfunction in GABAergic neurotransmission.     

Serotonin blocks the long-term potentiation induced by primed burst stimulation in the CA1 region of rat hippocampal slices.

The effect of 5-hydroxytryptamine on the induction of long-term potentiation by a train of high frequency pulses (100 Hz; 1 s) or by a stimulation consisting of one burst of five pulses at 100 Hz delivered 170 ms after a single pulse (primed burst) was investigated in the CA1 region of the rat hippocampal slice in vitro with extracellular recordings. Superfusion with 5-hydroxytryptamine (3-30 microM) produced a concentration-dependent decrease in amplitude of the population spikes evoked by test stimuli. The presence of 5-hydroxytryptamine (30 microM) did not affect the magnitude of long-term potentiation produced by the high-frequency stimulation but it prevented the long-term potentiation induced by a primed burst. The action of 5-hydroxytryptamine was mimicked by the 5-hydroxytryptamine1A agonist 5-carboxamidotryptamine (0.3 microM) and blocked by the 5-hydroxytryptamine2/5-hydroxytryptamine1A antagonist spiperone (3 microM) or by the 5-hydroxytryptamine1/5-hydroxytryptamine2 antagonist methiothepin (1-10 microM). The selective 5-hydroxytryptamine2 antagonist ritanserin (1 microM) did not antagonize the block of long-term potentiation produced by 5-hydroxytryptamine. The selective 5-hydroxytryptamine3 antagonists (3-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930; 1 nM) and ondansetron (GR-38032; 30 nM) did not affect the reduction in the population spike produced by application of 5-hydroxytryptamine. In contrast, a primed burst delivered at the fifth minute of 5-hydroxytryptamine application in the presence of a 5-hydroxytryptamine3 antagonist induced a long-term potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Different responses of CA1 and CA3 regions to hypoxia in rat hippocampal slice

1. To study the effects of brief periods of hypoxia on cellular functions in the rat hippocampal slice, extracellular and intracellular recordings were made from pyramidal neurons, and interstitial potassium activity ([K+]o) was measured in the pyramidal cell layers. Slices were perfused in an interface chamber at 36-37 degrees C with medium containing 8.5 mM [K+]o. Hypoxia was induced by switching the overflow gas from O2-CO2 to N2-CO2. 2. Brief periods of hypoxia (5-60 s) produced electrographic seizures with typical tonic and clonic components in 53% of 293 slices that generated spontaneous interictal bursts. Hypoxia-induced seizures were usually initiated in and restricted to the Ca1 region; only 2.5% of these slices generated seizures in CA3. In contrast to the CA1 region, the CA3 region could undergo spreading depression during hypoxia. The probability of seizure generation in CA1 was increased with increasing duration of hypoxia and was greatly reduced by lowering the bath temperature a few degrees. 3. [K+]o gradually increased in the CA1 and CA3 cell layers during the 20 s leading up to an hypoxia-induced seizure. [K+]o rose to approximately 9.8 mM (from a base line of 8.5 mM) in CA1 just before a seizure and to 11.4 mM during the seizure. After hypoxia, [K+]o reached a higher level in CA1 than in CA3, regardless of whether 1 microM tetrodotoxin was present to eliminate differences in cell firing in the two regions. CA1 pyramidal cells and glia gradually depolarized by several millivolts during and after hypoxia; no initial hyperpolarizing phase was detected. 4. Burst input from CA3 was necessary for hypoxia-induced seizures. The frequency and intensity of spontaneous burst-firing in CA3 remained steady in the period leading up to a CA1 seizure episode. In contrast, the intensity of synaptically driven bursts in CA1 grew markedly just before seizure onset. N-methyl-D-aspartate (NMDA) receptors participated in the crescendo of increasingly synchronous activity in CA1, because the competitive NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV, 30 microM), stereoselectively reduced seizure intensity. 5. Hypoxia-induced seizures were followed by a depressant phase, which was manifested most prominently by a prolonged (up to several minutes) reduction in the frequency and intensity of burst-firing in the CA3 region, hyperpolarization of CA1 neurons, and undershoot of [K+]o. In normal (3.5 mM) [K+]o, synaptically driven population spikes in CA1 were only reduced in amplitude by hypoxia; hypoxia did not induce seizures in 3.5 mM [K+]o.(ABSTRACT TRUNCATED AT 400 WORDS)     

Developmental changes in hyperexcitability of CA1 pyramidal neurons induced by repeated brief episodes of hypoxia in the rat hippocampal slices

We have previously demonstrated that repeated exposure of adult rat hippocampal slices to brief episodes of hypoxia induce a sustained decrease in the threshold of stimulus-evoked population spike discharges in CA1 pyramidal neurons [O. Godukhin, A. Savin, S. Kalemenev, S. Levin, Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca2+ channels, Neuropharmacology 42 (2002) 459-466, S.V. Kalemenev, A.V. Savin, S.G. Levin, O.V. Godukhin, Long-term potentiation and epileptiform activity induced by brief hypoxic episodes in CA1 area of the rat hippocampal slices. Russ. Physiol. J. 86 (2000) 1676-1681]. In the present study, using the above-mentioned in vitro model of epileptogenesis, we compared the developmental changes in hypoxia-induced hyperexcitability of CA1 neuronal network in the rat hippocampal slices prepared from three age rat groups: postnatal days (P) 13-14 (young), P60-70 (adult) and P600-650 (old). Furthermore, we were interested in learning about an age dependence of the hypoxia-induced changes in the efficacies of glutamatergic transmission and paired-pulse inhibition in CA3-CA1 synapses that may underlie ontogenetic differences in seizure susceptibility in hippocampal network. The principal results of this work are summarized as follow. In comparison with P60-70 hippocampal slices, CA1 pyramidal neurons in P13-14 and P600-650 slices showed intrinsically (without repeated brief hypoxa) an increased propensity to generate epileptiform stimulus-evoked population spike discharges. However, in contrast to adult and old animals, repeated brief episodes of hypoxia are incapable to induce a sustained decrease in the threshold of stimulus-evoked population spike discharges in CA1 pyramidal neurons of hippocampal slices prepared from of P13-14 rats, though they transform paired-pulse inhibition to paired-pulse facilitation and induce hypoxic LTP in CA3-CA1 synapses. The role of some other factors in the developmental changes in hyperexcitability of CA1 pyramidal neurons in response to repeated brief episodes of hypoxia is discussed.     

Sodium influx blockade and hypoxic damage to CA1 pyramidal neurons in rat hippocampal slices.

We studied the effects of lidocaine and tetrodotoxin (TTX) on hypoxic changes in CA1 pyramidal neurons to examine the ionic basis of neuronal damage. Lidocaine (10 and 100 microM) and TTX (6 and 63 nM) delayed and attenuated the hypoxic depolarization and improved recovery of the resting and action potentials after 10 min of hypoxia. Lidocaine (10 and 100 microM) and TTX (63 nM) reduced the number of morphologically damaged CA1 cells and improved protein synthesis measured after 10 min hypoxia. Lidocaine (10 microM) attenuated the increase in intracellular sodium (181 vs. 218%) and the depolarization (-21 vs. -1 mV) during hypoxia but did not significantly attenuate the changes in ATP, potassium, or calcium measured at 10 min of hypoxia. Lidocaine (100 microM) attenuated the changes in membrane potential, sodium, potassium, ATP, and calcium during hypoxia. TTX (63 nM) attenuated the changes in membrane potential (-36 vs. -1 mV), sodium (179 vs. 226%), potassium (78 vs. 50%), and ATP (24 vs. 11%) but did not significantly attenuate the increase in calcium during hypoxia. These data indicate that the primary blockade of sodium channels can secondarily alter other cellular parameters. The hypoxic depolarization and the increase in intracellular sodium appear to be important triggers of hypoxic damage independent of their effect on cytosolic calcium; a treatment that selectively blocked sodium influx (lidocaine 10 microM) improved recovery. Our data indicate that selective blockade of sodium channels with a low concentration of lidocaine or TTX improves recovery after hypoxia by attenuating the rise in cellular sodium and the hypoxic depolarization. This blockade improves the resting and action potentials, histologic state, and protein synthesis of CA1 pyramidal neurons after 10 min of hypoxia to rat hippocampal slices. A higher concentration of lidocaine, which also improved ATP, potassium, and calcium concentrations during hypoxia was more potent. In conclusion, the depolarization and increased sodium concentration during hypoxia account for a portion of the neuronal damage after hypoxia independent of changes in calcium.     

Chronic intermittent ethanol exposure alters CA1 synaptic transmission in rat hippocampal slices

We investigated the neuroadaptive changes in synaptic transmission in the CA1 region of the hippocampus as a result of chronic intermittent ethanol exposure. Male Wistar rats were exposed daily (14 h) to ethanol vapors (blood alcohol levels = 150-200 mg%) for 12-14 days, and synaptic field potentials elicited by Schaffer collateral stimulation were compared in hippocampal slices from control and chronic ethanol-treated rats. Excitatory postsynaptic responses of slices were recorded under three conditions: (i) normal physiological saline; (ii) continued presence of 33 mM (150 mg%) ethanol (chronic ethanol-treated rats only); (iii) acute exposure to 33 mM ethanol. When recorded in ethanol-free physiological saline, the mean amplitude of the dendritic synaptic potential and the somatic population spike were significantly smaller in slices from chronic ethanol-treated rats compared to slices from control rats. Under conditions of continuous ethanol exposure, somatic and dendritic synaptic responses of slices taken from chronic ethanol-treated rats were further depressed, suggesting that neural pathways in area CA1 remained sensitive to ethanol. Acute application of ethanol led to a more pronounced reduction of the mean somatic population spike amplitude in slices from chronic ethanol-treated rats than in slices from control rats. However, dendritic synaptic responses were unaffected by acute ethanol in slices from both control and chronic ethanol-treated rats. In addition, we examined the involvement of presynaptic mechanisms in the effects of chronic intermittent ethanol using paired-pulse protocols. When recorded in the continued presence of ethanol, slices from chronic ethanol-treated rats exhibited a significant reduction in paired-pulse facilitation of the dendritic synaptic response compared to slices from control rats, indicating a presynaptic component to the neuroadaptive effects of chronic intermittent ethanol exposure. Conversely, acute ethanol exposure resulted in an enhancement of paired-pulse facilitation of the dendritic synaptic response, an effect that was similar in slices from both control and chronic ethanol-treated rats. Paired-pulse facilitation of the somatic population spike amplitude was not altered by chronic ethanol treatment. However, acute ethanol exposure significantly enhanced paired-pulse facilitation of the somatic population spike in slices from chronic ethanol-treated rats. This effect of acute ethanol was not observed in slices from control rats. Paired-pulse inhibition was not significantly altered in slices from chronic ethanol-treated rats, suggesting that GABAergic inhibitory mechanisms were not involved in the neuroadaptive effects of chronic intermittent ethanol exposure. We suggest that chronic intermittent ethanol exposure can induce multiple neuroadaptive changes in synaptic transmission of CA1 pyramidal neurons that are detectable at both the pre- and postsynaptic levels. Alterations in paired-pulse facilitation indicate presynaptic changes involving the release of the excitatory neurotransmitter glutamate, whereas changes in dendritic synaptic responses suggest postsynaptic changes in the responsiveness of neurons to synaptic input. Moreover, differential effects of chronic ethanol treatment on synaptic responses recorded in the dendrites versus the somatic region implicate additional effects of ethanol on somatically located mechanisms of CA1 pyramidal neurons. Furthermore, we suggest that complete tolerance to ethanol does not occur in the CA1 region of the hippocampus following chronic intermittent ethanol exposure.     

Physiological heterogeneity of nonpyramidal cells in rat hippocampal CA1 region

Summary Functional differentiation of nonpyramidal cells was studied by intracellular recording and staining of cells located in the stratum pyramidale or along the border between the stratum radiatum and the stratum lacunosum-moleculare of slices prepared from rat hippocampal CA1 region. In the stratum pyramidale, nonpyramidal cells (fast-spiking cells, type I cells) exhibited brief-duration action potentials (mean spike-width at one-half amplitude = 0.28 ms, N = 9) and little or no frequency adaptation of spike discharge to depolarizing current pulse. These cells ramified axon collaterals mainly in the stratum pyramidale or in the apical side of the stratum oriens. The HRP-injected nonpyramidal cells located between the stratum radiatum and the stratum lanunosum-moleculare (type II cells) showed different physiological characteristics from fast-spiking cells in the stratum pyramidale. The spike width was longer than that of fast-spiking cells (mean duration measured at one-half amplitude = 0.61 ms, N = 11) and these cells exhibited adaptation of spike discharge in response to depolarizing current pulses. Following hyperpolarizing current pulses, a depolarizing potential was produced in some type II cells. Although most cells of this group sent axon collaterals into the stratum radiatum or into the stratum lacunosum-moleculare, there were also cells whose axon collaterals extended to and ramified in the stratum pyramidale. In contrast to pyramidal cells, spikes of both types of nonpyramidal cells did not broaden during repetitive firing evoked by large depolarizing current pulses. Stimulation of the stratum radiatum caused excitatory and inhibitory postsynaptic potentials in both type I and II cells. These results suggest that hippocampal nonpyramidal cells are divided into at least two groups; type I cells (fast-spiking cells) and type II cells.     

Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices

During hypoxia in the CA1 region of the rat hippocampus, spreading-depression-like depolarization (hypoxic spreading depression or HSD) is accompanied by both a negative shift of the extracellular DC potential (DeltaV(o)), and a sharp decrease in light transmittance (intrinsic optical signal or IOS). To investigate alterations in mitochondrial function during HSD and normoxic spreading depression (SD), we simultaneously imaged mitochondrial depolarization, using rhodamine-123 (R123) fluorescence, and IOS while monitoring extracellular voltage. Three major phases of the R123 signal were observed during hypoxia: a gradual, diffuse fluorescence increase, a sharp increase in fluorescence coincident with the HSD-related DeltaV(o), primarily in the CA1 region, and a plateau-like phase if reoxygenation is delayed after HSD onset, persisting until reoxygenation occurs. Two phases occurred following re-oxygenation: an abrupt and then slow decrease in fluorescence to near baseline and a slow secondary increase to slightly above baseline and a late recovery. Parallel phases of the IOS response during hypoxia were also observed though delayed compared with the R123 responses: an initial increase, a large decrease coincident with the HSD-related DeltaV(o), and a trough following HSD. After reoxygenation, there occurred a delayed increase in transmittance and then a slow decrease, returning to near baseline. When Ca(2+) was removed from the external medium, resulting in complete synaptic blockade, the mitochondrial response to hypoxia did not significantly differ from control (normal Ca(2+)) conditions. In slices maintained in low-chloride (2.4 mM) medium, a dramatic reversal in the direction of the IOS signal associated with HSD occurred, and the R123 signal during HSD was severely attenuated. Normoxic SD induced by micro-injection of KCl was also associated with a decrease in light transmittance and a sharp increase in R123 fluorescence but both responses were less pronounced than during HSD. Our results show two mitochondrial responses to hypoxia: an initial depolarization that appears to be caused by depressed electron transport due to lack of oxygen and a later, sudden, sharp depolarization linked to HSD. The depression of the second, sharp depolarization and the inversion of the IOS in low-chloride media suggest a role of Cl(-)-dependent mitochondrial swelling. Lack of effect of Ca(2+)-free medium on the R123 and IOS responses suggests that the protection against hypoxic damage by low Ca(2+) is not due to the prevention of mitochondrial depolarization.     

Glycine antagonists block the induction of long-term potentiation in CA1 of rat hippocampal slices

The effects of the strychnine-insensitive glycine receptor antagonists, cycloleucine and 7-chlorokynurenic acid, on the induction of long-term potentiation (LTP) in CA1 of rat hippocampal slices were examined. A 5 min administration of cycloleucine (20-100 microM) or 7-chlorokynurenic acid (1-5 microM) during the delivery of high-frequency stimulation blocked the induction of LTP without affecting baseline synaptic transmission. Coapplication of 100 microM glycine with cycloleucine or 7-chlorokynurenic acid masked the inhibitory effect on the induction of LTP, supporting the hypothesis that these compounds act as glycine antagonists. These results indicate that glycine is a necessary factor for the induction of LTP in CA1 of the rat hippocampus.     

Low-magnesium epilepsy in rat hippocampal slices: inhibitory postsynaptic potentials in the CA1 subfield

Spontaneous, synchronous epileptiform discharges were recorded in both CA3 and CA1 subfields of rat hippocampal slices perfused with Mg2+-free medium. Surgical separation of the two areas abolished the spontaneous discharges only in the CA1 subfield. However, epileptiform responses in the isolated CA1 subfield could still be evoked by orthodromic stimulation. Intracellularly these stimulus-induced responses were characterized by a depolarization associated with a burst of action potentials. Stimulation of the alveus still evoked a hyperpolarizing potential, presumably a recurrent inhibitory postsynaptic potential (IPSP) in CA1 pyramidal cells. Both spontaneous and stimulus-induced epileptiform discharges were blocked by the selective antagonist of N-methyl-D-aspartate (NMDA) receptors DL-2-amino-phosphonovalerate (APV). APV also reduced the amplitude and duration of the IPSP induced by alveus stimulation. Thus, epileptiform discharges evoked by lowering Mg2+ in the CA1 subfield are associated with a preservation of inhibitory mechanisms. Furthermore the effects exerted by APV upon the IPSP implicate that NMDA receptors might be involved in the neuronal circuit responsible for the hyperpolarizing IPSP generated by CA1 pyramidal neurons.     

Glucocorticoids promote localized activity of rat hippocampal CA1 pyramidal neurons in brain slices

The effects of glucocorticoids on rat hippocampal CA1 pyramidal neurons were studied using brain slice preparations. At 10 days after bilateral adrenalectomy, a localized region of CA1 showed a drastic reduction of excitability induced by CA3 stimulation as compared to control. The region of CA1 most effected was 1.4-2.0 mm from the most rostral side of the hippocampus. Upon perfusion of corticosterone, the response to synaptic activation was reduced in this region in slices from adrenalatomized animals increased rapidly toward control values, volatile responses in other regions were unaffected. These results suggest that glucocorticoid receptors are concentrated in restricted regions of hippocampus and that these receptors have important roles in regulation of synaptic excitability.