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P S Buckmaster

Publications and source records attributed to P S Buckmaster.

26 records · Page 2Linked to original sources

Interneurons and inhibition in the dentate gyrus of the rat in vivo.

Inhibitory cells are critically involved in shaping normal hippocampal function and are thought to be important elements in the development of hippocampal pathologies. However, there is relatively little information about the extent and pattern of axonal arborization of hippocampal interneurons and, therefore, about the sphere of influence of these cells. What we do know about these cells is based largely on in vitro slice studies, in which interneuronal interactions may be severely attenuated. The present study was carried out to provide a more realistic picture of interneuron influence. Intracellular recordings were obtained from dentate interneurons in the intact brain of anesthetized rats, and cells were intracellularly labeled with biocytin. The axonal arbors of two classes of dentate interneurons were traced through the hippocampus; each was found to extend long distances (up to half of the total septotemporal length of the hippocampus) perpendicular to the hippocampal lamellae and to target preferential strata. These results suggest that dentate interneurons have far-reaching effects on target cells in distant hippocampal lamellae. One implication of this finding is that dentate neurons should receive more inhibitory synaptic drive in vivo than in slice preparations, in which many inhibitory axon collaterals are amputated. Synaptic responses to perforant path stimulation were examined in granule cells, mossy cells, and CA3 pyramidal cells in vivo, for comparison with previously published results from hippocampal slice studies. In vivo, all cell types showed excitatory synaptic responses that were brief and limited by robust IPSPs that were larger in amplitude and conductance than responses to comparable stimuli recorded in vitro. This difference could not be explained by a change in the intrinsic physiological properties of the cells in the slice preparation, because those parameters were similar in vivo and in vitro. We conclude that dentate gyrus inhibitory interneurons can affect the excitability of neurons in distant areas of the hippocampus, and that these distant influences cannot be appreciated in conventional in vitro preparations.

Animals↗

Somatostatin-immunoreactivity in the hippocampus of mouse, rat, guinea pig, and rabbit.

The hippocampi of species commonly used for in vitro physiologic studies were examined to determine if there were species-specific and regional differences in somatostatin immunoreactivity. The distributions of somatostatin-immunoreactive somata and fiber plexuses were determined, and the concentration of somatostatin along the septotemporal axis of the hippocampus was measured using a radioimmunoassay. There are many similarities in the patterns of somatostatin immunoreactivity in the hippocampi of mice, rats, guinea pigs, and rabbits. All species had a relatively even distribution of somatostatin-positive perikarya across three fields of the hippocampus (dentate gyrus, CA3, and CA1-2), a similar distribution of somatostatin-immunoreactive perikarya across the strata of the CA1-2 field and the dentate gyrus; and more somatostatin-positive cells in temporal than in septal hippocampus. However, there are species-specific differences in the distribution of somatostatin-immunoreactive perikarya across the strata of CA3. In addition, unlike the other species examined, mice appeared not to have a somatostatin-immunoreactive fiber plexus in the molecular layer of the dentate gyrus. The functional significance of these differences remains to be determined.

Animals↗

Hyperexcitability in the dentate gyrus of the epileptic Mongolian gerbil.

There are anatomical differences in the hippocampi of seizure-resistant (SR) vs. seizure-sensitive (SS) Mongolian gerbils. SS gerbils have more GABAergic neurons and more GABAergic axon terminals contacting inhibitory basket cells in the dentate gyrus. Hence, it has been hypothesized that inhibition of basket cells causes disinhibition of granule cells and results in hyperexcitability in SS gerbils. To test this hypothesis we measured the level of excitability in the dentate gyrus of anesthetized adult SS and SR gerbils, using a paired-pulse stimulus paradigm to evoke population spikes. Population spikes of SS and SR gerbils both showed strong paired-pulse inhibition at short interstimulus intervals and paired-pulse facilitation at intermediate interstimulus intervals. However, compared to SR gerbils, SS gerbils had significantly stronger paired-pulse facilitation which persisted at longer interstimulus intervals. These results show that SS gerbils have hyperexcitable dentate gyri and support the view that less effective inhibition is an underlying basis for this hyperexcitability.

Anesthesia↗

Brainstem auditory evoked potential interwave intervals are prolonged in vitamin B-6-deficient cats.

Vitamin B-6 deficiency has been reported to produce behavioral, neurophysiological and neuropathological abnormalities in a variety of species. In this investigation we used brainstem auditory evoked potentials (BAEP) to determine if vitamin B-6 deficiency in cats affected peripheral and brainstem auditory pathways. Brainstem auditory evoked potentials were recorded from growing cats as they developed vitamin B-6 deficiency, which was confirmed using clinical, hematological and urinary criteria. The BAEP interwave intervals measured from early (wave 1 or 1N) to late waves (5N) or from middle (wave 3) to late waves increased significantly, whereas interwave intervals from early to middle waves did not differ significantly. These results indicate that vitamin B-6 deficiency affects one or more structures of the brainstem that generate the later parts of the BAEP. The finding of prolonged interwave intervals in vitamin B-6-deficient animals is consistent with slowed axonal conduction velocity secondary to defective myelination. Recording BAEP provided a noninvasive means of detecting effects of vitamin B-6 deficiency on specific parts of the central nervous system.

Acoustic Stimulation↗

A comparison of rat hippocampal mossy cells and CA3c pyramidal cells.

1. There is a long-standing debate about whether the large spiny cells in the hilar region of the hippocampus should be classified as pyramidal cells of Ammon's horn or as a distinct cell type of the dentate gyrus. The rationale for grouping these hilar neurons (termed "mossy cells") with pyramidal cells of Ammon's horn is shared characteristics. In the present study we have compared the morphological and physiological characteristics of mossy cells and nearby CA3c pyramidal cells with the use of a rat hippocampal slice preparation. 2. Biocytin-labeled neurons were examined on the basis of soma area, location, shape, number of primary dendrites, extent of dendritic spines, dendritic location, and axon trajectories. Mossy cells had larger soma areas than CA3c pyramidal cells, and they had more large complex spines (thorny excrescences) on their proximal dendrites and somata than CA3c pyramidal cells. Mossy cell dendritic trees and axon collaterals ramified in different regions of the hippocampus than dendrites and axons of CA3c pyramidal cells. 3. Intrinsic physiological properties, and spontaneous and evoked synaptic properties, were measured and compared. Mossy cells had significantly higher input resistances, smaller amplitude burst afterhyperpolarizations, smaller amplitude action potentials, less spike-frequency adaptation, and more anomalous rectification than CA3c pyramidal cells. 4. Mossy cells had spontaneous excitatory postsynaptic potentials (EPSPs) that were significantly higher in frequency and larger in amplitude than CA3c pyramidal cells. A larger proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with depolarizing postsynaptic potentials without any apparent hyperpolarization. Conversely, a smaller proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with inhibitory postsynaptic potentials (IPSPs), and spontaneous IPSPs were more difficult to detect in mossy cells. 5. The intrinsic physiological properties of mossy cells endow these cells with potent excitatory mechanisms but relatively fewer inhibitory control processes than CA3c pyramidal cells. Recordings of spontaneous and evoked PSPs suggest that mossy cells receive more excitatory input and less inhibitory input than CA3c pyramidal cells. These intrinsic and synaptic properties of mossy cells may explain this cell type's exceptional vulnerability to excitotoxic damage by intense afferent stimulation. 6. In summary, mossy cells were significantly different from CA3c pyramidal cells in many of their morphological, intrinsic physiological, and synaptic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Potentiation of spontaneous synaptic activity in rat mossy cells.

Recent studies have demonstrated the vulnerability of dentate mossy cells to seizure-induced damage. One source of potentially damaging synaptic input are spontaneously active granule cell terminals ('mossy terminals'.) We sought to test whether there were activity-dependent changes in the spontaneous excitatory input to mossy cells. Using the in vitro slice preparation, we examined the frequency and amplitude of spontaneous excitatory postsynaptic potentials (EPSPs) after intracellular current injection designed to mimic the extreme depolarization these neurons receive during repetitive afferent stimulation. In 4 of 7 neurons, depolarization with trains of current pulses resulted in a significant and persistent increase in frequency of spontaneous synaptic depolarizations (to an average of 178% of the initial baseline rate). In 3 of these affected neurons, an increased frequency of large amplitude, fast-rising EPSPs accounted for the majority of this change. Injection of hyperpolarizing current pulses failed to alter spontaneous activity in 3 other mossy cells. These results suggest spontaneous synaptic input to mossy cells in plastic and can be potentiated by depolarization of a single postsynaptic mossy cell. The ability of mossy cells to potentiate their excitatory input may be relevant to their vulnerability to excitotoxic injury during repetitive afferent stimulation.

Animals↗

Mossy cell axonal projections to the dentate gyrus molecular layer in the rat hippocampal slice.

The ipsilateral associational pathway connects different septotemporal levels of the dentate gyrus. Neurons of the dentate hilus project hundreds of micrometers from the cells of origin to the inner molecular layer. The authors hypothesized that mossy cells, the major cell type of the hilus, also project locally to the inner molecular layer. Within a 400 microns slice, mossy cells were (1) recorded intracellularly while the inner molecular layer was stimulated to test for antidromic responses, and (2) labeled with biocytin and examined with light and electron microscopy for axonal projections into the molecular layer. The authors found that mossy cells can be antidromically activated by inner molecular layer stimulation and that axonal projections to the molecular layer can be visualized within a 400 microns hippocampal slice. In 13 of 19 intracellularly labeled and electrophysiologically characterized mossy cells, collaterals could be traced into the molecular layer. These results suggest that mossy cells contribute to the ipsilateral associational pathway and also participate in local recurrent circuitry to influence granule cell activity.

Action Potentials↗