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Calbindin-D28K and ischemic damage of pyramidal cells in rat hippocampus.

An antibody against rat calbindin-D28K, a calcium-binding protein present at high concentration in certain neurons of the central and peripheral nervous systems, was used to determine the progression of the pathological events in the rat hippocampus following experimental cerebral ischemia. Calbindin-D28K immunoreactivity is present in dentate granule cells and in the CA1-CA2 pyramidal cells. CA1 subfield contains a higher proportion of calbindin-D28K-positive pyramidal cells than does the CA2 subfield and CA1 cells are more immunoreactive than the CA2 cells. The pyramidal cells of the CA1 and CA2 subfields are vulnerable to ischemia. The cells in the CA1 became necrotic within 3-4 days after ischemia while those of the CA2 became necrotic within 2 days. There was a concomitant decrease in calbindin-D28K immunoreactivity in the whole hippocampal regio superior after ischemia which peaked 3 days postischemia. The difference in CA2 and CA1 vulnerability seemed to be inversely correlated with the calbindin-D28K contents of the CA2 and CA1 pyramidal cells. The decrease in the calbindin-D28K contents of these neurons was accompanied by cell damage. We therefore suggest that calbindin-D28K is an important factor for the survival of pyramidal cells in the hippocampal formation after ischemia.

Animals

Thyroid hormone and development of the rat hippocampus: morphological alterations in granule and pyramidal cells.

A quantitative study of the morphogenesis of granule and pyramidal cells was performed on Golgi-Cox preparations of the developing hippocampus of normal and hypothyroid rats, and hypothyroid rats given replacement thyroxine treatment. In the normal hippocampus, the volume of the cell body and the number of branching points on the apical and on the basal dendrites of pyramidal cells increased between 6 and 10 days after birth. The pyramidal cells of Ammon's horn showed a gradation from area CA1 to area CA4 of progressive differentiation. In thyroid-deficient rats, the arborization of the dendritic field of both granule and pyramidal cells was impaired, and for pyramidal cells the extent of the impairment depended on the position of the cells in the Ammon's horn, the cells of CA3-4 areas being the most affected. Treatment of hypothyroid rats with a physiological dose of thyroxine restored some of the morphological defects to normal, but others were altered beyond control levels, indicating that thyroid hormone differentially controls not only the measured indices of maturation but also that its influence depends on the position of the pyramidal cells. The observations were consistent with the concept that thyroid hormone is important in the establishment of the CA1 to CA4 gradient of pyramidal cell differentiation and in the development of the spatiotemporal relationship between pyramidal and granule cells of the hippocampus.

Animals

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions.

Four different types of axon terminals form symmetric synapses with the cell bodies and initial axon segments of pyramidal cells in layer II/III of rat visual cortex. One type belongs to chandelier cells, and the other three kinds of terminals have origins that have not been established yet. These latter are referred to as large, medium-sized and dense terminals. The purpose of the present study was to examine the synaptic junctions formed by all four types of terminal. The synapses formed by the chandelier cell terminals are readily recognized in thin sections because of the characteristics features of both the terminals and the initial axon segments, which are the neuronal elements postsynaptic to them. In en face views of these axo-axonal synapses the junctions can be seen to have presynaptic dense projections that form a grid in which they are triagonally spaced, and have an average centre-to-centre spacing of 84 nm. As an ensemble the projections form the presynaptic grid, which usually has an oval or round outline, but may be notched on one side where projections are absent. The synaptic junctions of the large, medium-sized and dense terminals were examined by making reconstructions of the terminals from serial thin sections. It was found that at the interfaces between the axon terminals and the cell bodies of pyramidal cells, several separate synaptic junctions may be present, in addition to a number of puncta adhaerentia. Thus, there may be as many as five separate synaptic junctions and as few as one.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The N-methyl-D-aspartate antagonists aminophosphonovaleric acid and MK-801 reduce anoxic damage to dentate granule and CA1 pyramidal cells in the rat hippocampal slice.

The effect of the N-methyl-D-aspartate antagonists, aminophosphonovaleric acid and MK-801, on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from either the dentate granule cells or the CA1 pyramidal cells and the amplitude of this spike was compared before and 60 min following anoxia. After 10 min of anoxia the dentate granule cells recovered to 16 +/- 7% (mean +/- SE) of their preanoxic level when untreated and to 54 +/- 15% when treated with aminophosphonovaleric acid (APV). In slices treated with MK-801 the population spikes recorded from dentate granule cells recovered to 85 +/- 4% of their preanoxic level after 10 min of anoxia. Untreated CA1 pyramidal cells recovered to 8 +/- 3% of their preanoxic amplitude after 5 min of anoxia; they recovered to 59 +/- 6% when treated with MK-801 and 31 +/- 13% when treated with APV. The recovery of slices treated with the drugs was significantly different from that of untreated slices. ATP levels were measured in both the dentate and the CA1 region of slices. ATP in both regions fell less during anoxia when the slices were pretreated with either APV or MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801 in dentate tissue after 10 min of anoxia and with MK-801 in CA1 tissue after 5 min of anoxia. This reduced fall in ATP during anoxia was accompanied by better physiological recovery after anoxia. We conclude that these NMDA antagonists provide protection against anoxic damage to dentate granule and CA1 pyramidal cells in this in vitro hippocampal preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate

[Quantitative study of primitive pyramidal cells in rat anterior cingular cortex].

In the present paper the primitive pyramidal cells of the Vthlayer of the anterior cingulate cortex in adult male white rats were analyzed quantitatively and compared statisticaly with large pyramidal cells of the same region. The number of dendrites, the total lengths of dendrites, the number of spines and the density of spines -- according to the order of dendrites -- show similarity between the primitive pyramidal cells and the large pyramidal cells the latter one exhibit the higher values. The curves of distribution of the various density of spines along the apical main dendrite of both cell types are similar in shape, too. The lengths of the dendritic fields and their basal spines-values are without significant distinction for both cell types, however there are more dendritic fields in large pyramidal cells. Refered to a complete pyramidal neuron they can say: there are significantly higher values in large pyramidal cells for the number of dendrites and their total lengths, the total number of spines, the number of branching sites sites and free endings. However the density of spines of the complete neuron has no significant differences between primitive and large pyramidal cells.

Animals

N-methyl-D-aspartate receptor activation and Ca2+ account for poor pyramidal cell structure in hippocampal slices.

The CA1 pyramidal cells appear damaged in micrographs of guinea pig hippocampal slices incubated in normal physiological buffer at 36-37 degrees C. This is remedied if slices are incubated in modified buffers for the first 45 min. Cell morphology is improved if this buffer is devoid of added Ca2+ and much improved if it contains N-methyl-D-aspartate (NMDA) receptor antagonists or 0 mM Ca2+ and 10 mM Mg2+. The cells then appear similar to CA1 pyramidal cells in situ. These findings support the notion that NMDA receptor activation and Ca2+, acting in the period immediately after slice preparation, permanently damage CA1 pyramidal cells in vitro.

Adenosine Triphosphate

Electrical activities of pyramidal cells in the kindled hippocampus of the rabbit.

1) The pyramidal cell in the kindled hippocampus of the rabbit was intracellularly studied and compared with that in the normal hippocampus. 2) As previously reported, what characterized the kindled hippocampus was the appearance of a spontaneous hyperpolarization in the pyramidal cell. Practically all the pyramidal cells in the kindled hippocampus showed spontaneous hyperpolarizations. The hyperpolarization consisted of Cl-dependent and Cl-non-dependent components. The former was evidently the somatic IPSP. On the other hand, the latter was interpreted as the dendritic IPSP. This was supported by the fact that there was an interictal positivity in the apical dendrite layer. 3) There was no evidence whatsoever that indicated an increased excitability of the pyramidal cell. This showed that the kindled hippocampus was essentially different from the penicillin-treated hippocampus. It was suggested that the former was similar to the human brain in the interictal phase, whereas the latter was similar to that in status epilepticus. 4) In a few pyramidal cells there was a slow depolarization which could possibly trigger a seizure discharge and the nature of the slow depolarization was discussed. However, the slow depolarization was not peculiar to the kindled hippocampus.

Action Potentials

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. I. Morphometric analysis.

An examination of material prepared for conventional electron microscopy has indicated that there are at least four different types of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells in the rat visual cortex. One type of terminal synapses with the initial axon segment and it is derived from the chandelier cell. Because the location and features of these terminals allow them to be readily recognized, chandelier cell terminals were used to determine the extent of morphometric variability that can exist among terminals originating from one cell type. It was found that there is a wide range of mean synaptic vesicle size among chandelier terminals, so that calculated mean vesicle profile diameters for individual terminals can be between 32 and 39 nm. Similar ranges of mean synaptic vesicle sizes also exist among populations of the other three axon terminal types. These terminal types are referred to as 'large', 'medium-sized', and 'dense' terminals. The large terminals synapse with the cell bodies of layer II/III pyramids and their profiles often measure 1.5 X 0.8 microns. The large terminals contain rather loosely packed pleomorphic vesicles and they frequently synapse with a second neuronal element. The medium-sized terminals are smaller, being 1.0 X 0.6-0.8 microns in size, and their synaptic vesicles are usually more closely packed than those within the large terminals. The medium-sized terminals are the ones encountered most frequently on the cell bodies of pyramidal cells and they can also occur on the axon hillock and initial axon segment. The dense terminals are usually flattened against the cell body, and they contain rather rounded and closely packed synaptic vesicles, which often seem to be enmeshed in a rather dark cytoplasmic matrix. This matrix and the close packing of the vesicles makes these terminals appear to be more dense than the others. It is now necessary to determine the origins of the large, medium and dense terminals, and to ascertain if they all use GABA as their neurotransmitter.

Animals

Local circuit interactions between oriens/alveus interneurons and CA1 pyramidal cells in hippocampal slices: electrophysiology and morphology.

Electrophysiological and anatomical techniques were used to determine the role, in the hippocampal circuitry, of local circuit neurons located at the oriens/alveus border (O/A interneurons). Intracellular recording from these cells showed that their response characteristics were clearly nonpyramidal: high input resistance, short membrane time constant, short-duration action potential, pronounced, brief afterhyperpolarizations (AHP), and nondecremental firing during intrasomatic depolarizing current pulses. Intracellular Lucifer yellow (LY) injection and subsequent fluorescence microscopy confirmed their nonpyramidal nature. O/A interneuron somata were bipolar or multipolar; their dendrites projected mostly parallel to the alveus, except for 1 or 2 processes that turned perpendicularly, and ascended through stratum oriens and pyramidale and into radiatum. Their axons were seen to branch profusely in stratum oriens and pyramidale. Simultaneous intracellular recordings from O/A interneurons and CA 1 pyramidal cells showed that pyramidal cells directly excite these interneurons. Major hippocampal afferents also directly excited the O/A interneurons. In a small number of interneuron-pyramidal pairs, stimulation of the O/A interneuron directly inhibited pyramidal cells. In one case, reciprocal connections were observed: The pyramidal cell excited the interneuron, and the interneuron inhibited the pyramidal cell. In 1 interneuron-to-interneuron pair, an inhibitory connection from O/A interneuron to stratum pyramidale interneuron was also observed. With intracellular HRP injections into O/A interneurons and subsequent electron microscopy, we observed that O/A interneuron axons made contacts with pyramidal and nonpyramidal cells. HRP-filled symmetric synaptic contacts were found on pyramidal cell dendrites and somata. HRP-filled axons also made contacts with pyramidal cell initial segments. HRP-filled O/A interneuron axon contacts were also found on nonpyramidal cell dendrites in stratum oriens. These electrophysiological and anatomical results suggest that O/A interneurons make synaptic contact with pyramidal cells and may mediate feedforward and feedback inhibition onto CA 1 pyramidal cells.

Animals

Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone.

In order to determine whether pyramidal cells of the adult hippocampus are morphologically sensitive to thyroid hormone, we performed single-section Golgi impregnation analyses on brains from hyperthyroid and control rats. Quantitative analyses of Golgi-impregnated pyramidal cells from the CA1 region showed a significant decrease in the density of apical dendritic spines with hyperthyroidism. In contrast, no changes were observed in spine density of basal dendrites or in cross-sectional cell body area of CA1 pyramidal cells. No changes in any of these morphological variables were detected in pyramidal cells of the CA3 region with hyperthyroidism. These results suggest that spine density of the apical dendrites of CA1 pyramidal cells is specifically affected by thyroid hormone in adulthood. Since dendritic spines are thought to represent postsynaptic sites it is likely that this morphological change results in altered hippocampal function.

Animals

Mu opioid receptor activation reduces inhibitory postsynaptic potentials in hippocampal CA3 pyramidal cells of rat and guinea pig.

Using intracellular recording techniques, we characterized synaptic responses of CA3 pyramidal cells to mu and kappa agonists in hippocampal slices from rats and guinea pigs. In rat CA3 pyramidal cells, the mu selective agonist (N-MePhe3,D-Pro4)-morphiceptin (PLO17) inhibited both the early and the late inhibitory postsynaptic potentials (IPSPs) and increased excitatory postsynaptic potential (EPSP) amplitudes. Voltage clamp analysis of synaptic currents indicated that the excitatory postsynaptic current were not increased by PLO17, showing that the apparent increase in EPSPs was a result of a decrease in the underlying IPSP. The kappa agonists trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate and dynorphin A (1-17) had no effect on EPSPs or IPSP conductances measured in rat pyramidal cells. Maximal inhibition of IPSPs by PLO17 resulted in a bursting response to stimulation in rat but not guinea pig CA3 pyramidal cells. In guinea pig CA3 pyramidal cells, PLO17 also inhibited IPSP conductances but did not affect EPSP amplitudes. In contrast to the lack of effect in rat pyramidal cells, trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate (100 nM) inhibited the late IPSP conductance without influencing the EPSP or the early IPSP conductance of guinea pig pyramidal cells. Dynorphin A (1-17) (0.01-10 microM) did not affect resting membrane properties or evoked synaptic conductances in either preparation. Mu receptor activationin the CA3 of rats and guinea pigs results in the inhibition of inhibitory synaptic input to pyramidal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sex differences and thyroid hormone sensitivity of hippocampal pyramidal cells.

In an effort to determine if sex differences exist in the morphologic characteristics of pyramidal cells and granule cells of the hippocampal formation and whether sex plays a role in determining thyroid hormone sensitivity of these neuronal populations, we used single-section Golgi impregnation to examine the effects of neonatal thyroid hormone administration on hippocampal cells from the brains of adult rats of both sexes. Quantitative analyses of control brains revealed sex differences in the number of primary dendrites and the number of spines on the apical dendritic shaft of CA3 pyramidal cells. These differences showed opposite trends; females possessed more primary dendrites, whereas males showed more apical excrescences. Neonatal treatment with thyroid hormone resulted in long-lasting and dramatic changes of the entire CA3 pyramidal cell. CA3 pyramidal cells from thyroid hormone-treated animals showed significantly larger cell body areas, greater numbers of dendritic branchpoints, and longer dendrites. In addition, CA3 pyramidal cells from thyroid hormone-treated animals showed changes in the morphological characteristics which were shown to be sexually dimorphic; treatment resulted in significantly greater numbers of both primary dendrites and apical excrescences. These treatment differences occurred in both sexes and were of equal magnitude, regardless of sex. On the other hand, no sex differences in the morphologic parameters examined were detected for pyramidal cells in the CA1 region. Moreover, neonatal thyroid hormone treatment did not affect the cell body area, dendritic branch points, or the length of dendrites of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge.

The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of "place cell" discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional "trisynaptic circuit". These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.

Animals

Local circuit synaptic interactions between CA1 pyramidal cells and interneurons in the kainate-lesioned hyperexcitable hippocampus.

Following kainate (KA)-induced lesions of subfield CA3--a lesion relevant to human temporal lobe epilepsy--remaining pyramidal cells in CA1 display synchronous hyperexcitability associated with a loss of synaptic inhibition. Despite this loss, inhibitory interneurons in CA1 remain viable, and the density and function of GABAergic receptors on the CA1 pyramidal cells are maintained at approximately normal levels. To further evaluate inhibition in this system, the authors examined interactions between pyramidal cells and inhibitory interneurons in paired intracellular recordings. Recordings were carried out in rat hippocampal slices 2-4 weeks following bilateral intraventricular KA injections. The frequency of synaptic interactions between CA1 basket cells and pyramidal cells was lower in hyperexcitable slices than in controls; both synapses in the recurrent inhibitory circuit appeared to be involved. No recurrent excitatory interactions were seen between pyramidal cell pairs in lesioned or normal slices. The weakened interconnections between pyramidal cells and interneurons are consistent with the decreased inhibition previously found in this model. Unexpectedly, strong stimulation, which may directly activate local inhibitory circuitry, was effective in reducing hyperexcitability in KA-lesioned slices. These data suggest that development of recurrent excitatory connections among CA1 hippocampal pyramidal cells contribute little to tissue excitability, and support the hypothesis that a functional uncoupling between inhibitory interneurons and CA1 pyramidal cells is responsible for the seizure-like activity typical of KA-lesioned hippocampus. The data are also consistent with the hypothesis that in the KA model, the structural circuitry needed for inhibition in CA1 is maintained, and can be functionally activated by appropriate stimuli.

Animals

Synaptic targets of HRP-filled layer III pyramidal cells in the cat striate cortex.

There are numerous hypotheses for the role of the axon collaterals of pyramidal cells. Most hypotheses predict that pyramidal cells activate specific classes of postsynaptic cells. We have studied the postsynaptic targets of two layer III pyramidal cells, that were of special interest because of their clumped axon arborization near, and also 0.4-1.0 mm from the cell body, in register in both layers III and V. 191 terminations from four sites (layers III and V, both in the column of the cell and in distant clumps) were analysed by electron microscopy. Only one bouton contacted a cell body and that was immunoreactive for GABA. The major targets were dendritic spines (84 and 87%), and the remainder were dendritic shafts. Of these 13 were classed as pyramidal-like (P), 8 smooth cell-like (S) and three could not be classified. Four of five S types, but none of the seven P types tested were immunoreactive for GABA, supporting the fine structural classification. The putative inhibitory cells therefore formed not more than 5% of the postsynaptic targets, and their activation could only take place through the convergence of pyramidal cells onto a select population of GABA cells. The results show that the type of pyramidal cells with clumped axons studied here make contacts predominantly with other pyramidal cells. Thus the primary role of both the intra and intercolumnar collateral systems is the activation of other excitatory cells.

Animals

GABAergic inhibition shapes temporal and spatial response properties of pyramidal cells in the electrosensory lateral line lobe of gymnotiform fish.

1. The amplitude-coding pyramidal neurons of the first-order nucleus in weakly electric gymnotiform fish (Eigenmannia), the electrosensory lateral line lobe (ELL), exhibit 2 major physiological transformations of primary afferent input. Pyramidal cells rapidly adapt to a step change in amplitude, and they have a center/surround receptive-field organization. This study examined the physiological role of GABAergic inhibition on pyramidal cells. GABAergic synapses onto the somata of pyramidal cells primarily originate from granule-cell interneurons along with descending input. 2. Pyramidal cells fall into two physiologically distinct categories: E units, which are excited by a rise in stimulus amplitude, and I units, which are inhibited by a rise in stimulus amplitude. Microiontophoretic application of bicuculline methiodide onto both types of pyramidal cells increased the time constant of adaptation, defined as the time required for the neuron's response to decay to 37% of its maximum value, by 70-90%. The peak firing rate of E units to a step increase in stimulus amplitude increased by 49%, while the firing rate of I units did not change significantly. 3. Bicuculline application demonstrated that GABAergic inhibition may contribute to the strict segregation of E and I response properties. In the presence of bicuculline, many E units (normally excited only by stimulus amplitude increases) became excited by both increases and decreases; many I units (normally excited only by amplitude decreases) also became excited to increases. 4. The size of the excitatory receptive-field of E units was not affected by bicuculline, although response magnitude increased. The inhibitory surround increased in spatial extent by 175% with bicuculline administration. Neither the size of the I unit receptive-field center nor the response magnitude changed in the presence of bicuculline. The antagonistic surround of I units, however, increased by 49%. 5. The anatomy of the ELL is well understood (see Carr and Maler 1986). The physiological results obtained in this study, along with the results of Bastian (1986a, b), further our understanding of the functional role of the ELL circuitry. Our results suggest that spatial and temporal response properties of pyramidal cells are regulated by different but interacting inhibitory interneurons, some of which use GABA as a neurotransmitter. The activity of these interneurons is in turn controlled by descending feedback systems.

Action Potentials

Differential effects of methionine5-enkephalin on hippocampal pyramidal cells and interneurons.

While the excitatory action of opioids and opiate drugs upon pyramidal neurons in the hippocampus is well known, the mechanism by which this excitation is achieved is still argued. A popular hypothesis is that opiates reduce the activity of inhibitory interneurons, thereby indirectly exciting the pyramidal cells. To validate this idea, it is necessary to show that opiates selectively affect the population of interneurons. The present study therefore examined the effects of met-enkephalin upon pyramidal cells and interneurons located in area CA1. Extracellular action potentials were recorded using multibarrelled micropipettes. Drugs were applied locally by either pressure micro-ejection or microiontophoresis. Met-enkephalin (10(-5) M) elevated the spontaneous discharge of pyramidal cells, while interneurons were inhibited. The responses of both types of cell were blocked by the opiate antagonist naloxone. When the synaptic connections between the pyramidal cells and interneurons were disrupted by local application of magnesium or bicuculline, met-enkephalin had no effect on the pyramidal cells. However, neither magnesium nor bicuculline altered the enkephalin-induced inhibition of theta neurons. These results support the hypothesis that opioids of the enkephalin subclass, excite pyramidal cells in the hippocampus through a disinhibition mechanism.

Action Potentials

A grease-gap method for studying the excitatory amino acid pharmacology of CA1 hippocampal pyramidal cells.

A grease-gap method for studying the pharmacology of CA1 hippocampal pyramidal cells was developed with use of rat hippocampal slices that included only area CA1 and the retrohippocampal area. These slices were transferred to a two-compartment superfusion chamber and the pyramidal cell bodies in area CA1 were separated from their axons in the subiculum with a grease barrier. The CA1 pyramidal cells were depolarized relative to their axons by superfusion with N-methyl-D-aspartate (NMDA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and L-glutamate. NMDA was unusually potent in the CA1-subiculum slice compared to other preparations. The NMDA receptor antagonists D(-)-2-amino-5-phosphonovalerate (D-AP5), phencyclidine and Mg2+ shifted the NMDA dose-response curve to the right in a parallel manner. Similarly, the quisqualate receptor antagonist pentobarbitone shifted the AMPA dose-response curve to the right. Schild plots for these antagonists had slopes insignificantly different from 1. These results are consistent with the presence of a substantial NMDA receptor reserve on CA1 pyramidal cells. They are also in line with the high density of excitatory amino acid receptors on CA1 hippocampal pyramidal cells and with the known pharmacological properties of these receptors. Grease-gap studies on the CA1-subiculum slice fill the need for a means of obtaining quantitative pharmacological data on CA1 pyramidal cells.

2-Amino-5-phosphonovalerate