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Notes: Summary The participation of physiologically identified hippocampal neurons in spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane. Dentate granule cells were identified by their orthodromic response to perforant path stimulation, CA1 and CA3 pyramids by antidromic activation from the alveus and Schaffer collaterals, respectively, and basket cells by their response to increasing orthodromic activation. The discharges of many hippocampal cells were grossly correlated to the pattern of slow wave activity. Few cells were spontaneously active during irregular slow wave activity. With the appearance of rhythmical slow wave activity of 4–6 Hz, the unit discharges also increased in frequency. Dentate granule cells had the lowest threshold for activation and also a longer duration of the increased discharge frequency, compared to other cell types. There was a characteristic pattern of transition for dentate granule cells and CA1 pyramidal cells from a silent to an active state. The cell discharges paralleled the changes in amplitude, regularity, and frequency of theta slow waves. Large-amplitude, high-frequency theta was correlated with rhythmic burst discharges of up to 2–3 spikes per burst. As theta amplitude and frequency decreased, the number of spikes per burst reduced until only regular single spikes occurred. When theta activity was replaced by irregular slow wave activity, the cell discharges became irregular and sometimes ceased entirely. At high levels of activation, CA1 pyramids often showed clusters of high-frequency discharges with declining amplitude (complex spikes). For each cell a cycle histogram was constructed, placing the discharges in one of 20 bins according to their time relation to the simultaneously recorded slow theta waves. In addition, by Fourier transformation of the cycle histograms, the technique allowed a quantitative description of the degree and type of rhythmicity. The analysis indicated that virtually all dentate granule cells and CA1 pyramidal cells were phaselocked to the negative portion of the theta waves recorded from the corresponding region. The cells differed in their degree of coupling, as expressed by the modulation index of their cyclic histograms. Dentate granule cells had higher modulation indices than the CA1 pyramids. There was a suggestion that basket cells and CA3 cells had smaller modulation indices, but the low number of cells recorded mitigate against any strong conclusions. The results are interpreted as corroborating earlier findings that the dentate granule region and the CA1 pyramidal region are the main generators of hippocampal theta activity. A “size principle” was proposed to explain the role of synaptic depolarizing pressure in the rhythmic activation of hippocampal neurons and the fact that small neurons (dentate granules and CA1 pyramids) were better driven than larger neurons.

Notes: Summary In isolated transverse hippocampal slices GABA (gamma-amino-butyric acid) was applied iontophoretically to various parts of the dendritic tree of CA1 pyramidal cells. Indices of GABA effects were reduced amplitude of orthodromically driven CA1 population spikes and inhibition of single CA1 units driven by orthodromic stimulation or by application of L-glutamate. Weak iontophoretic currents of GABA (3–6 nA, backing current -3 nA) effectively reduced the amplitude of the population spike and arrested unit activity when applied in a position close to the soma. The effect was halved when GABA was applied 25–30 μm away at right angles to the main dendritic axis. In the direction of the main dendritic axis, GABA was effective as far as 250 and 150 μm from the soma in the apical and basal dendritic directions, respectively, corresponding to about 50% of the total dendritic length. The best effect was usually found at a depth corresponding to that of the recording electrode, probably because the main dendritic axis was parallel to the slice surface. The sharp localization of GABA sensitivity when applied in the pyramidal layer supports earlier evidence that GABA mediates the basket cell inhibition on the soma of the pyramidal hippocampal cells. In the dendritic tree, GABA may also have an inhibitory function with an effectiveness matching that of the soma application.

Notes: Summary Intra- and extracellular recordings were obtained from the CA1 region of guinea pig hippocampal slices maintained in vitro. We studied the effect of reducing the extracellular sodium concentration on penicillin-induced epileptiform responses. In control experiments, Tris and choline were assayed as sodium substitutes. Choline was found unsuitable, since it induced repetitive firing in the absence of any convulsant agent. Replacement of 50% of the extracellular sodium ([Na+]o) with Tris reduced the amplitude of the presynaptic fiber volley, the field EPSP, and the population spike. Intracellular studies showed that when [Na+]o was lowered, action-potential amplitudes were reversibly depressed by an amount close to that predicted by the Nernst relation. Orthodromically elicited epileptiform discharges, induced by penicillin, were reduced in a low-sodium medium when constant stimulus currents were employed. If orthodromic stimulus strengths in normal and low-sodium states were equated on the basis of the field-EPSP amplitude, no significant diminution of the depolarizing-wave component of the epileptiform response was observed. These results suggest that a synaptic component underlies penicillin-induced epileptiform discharges.

Notes: Abstract Alcaptonuria is a rare, hereditary disorder of amino acid metabolism, secondary to lack of homogentisic acid oxydase. As a consequence, there is ex accumulation of homogentisic acid, which is excreted in the urine and deposited in the connective tissues. This deposition results in ochronotic pigmentation and arthropathy, of which some characteristic radiological findings are demonstrated.