No abstract

Stimulation of the perforant path induces a long-lasting increase in the area of dendritic spines, which are sites of termination of the stimulated pathway in the distal third of the dentate molecular layer. No enlarged spines were found in the proximal third of the dentate molecular layer, where the commissural afferents terminate. Following a single tetanic stimulus of 30 sec duration at 30/sec, spines became significantly larger by 15%, 38%, 35% and 23% within poststimulation intervals of 2-6 min, 10-60 min, 4-8 h, and 23 h, respectively. Axon terminals decreased their area by 15% within the 2-6 min interval and the vesicle density was decreased by 19% within the 10-60 min interval. Both changes were reversible and terminals resumed their prestimulation condition at longer intervals (greater than 4 h). The initial enlargement of spines was interpreted as being due to a glutamate-induced increase in the sodium permeability of the spine membrane, whereas for the long-lasting enlargement an increase in protein synthesis was postulated. The long-lasting enlargement of dendritic spines in the dentate molecular layer following a short train of stimuli delivered to the perforant path, supports the postulate which links such a change to the mechanism of long-lasting postactivation potentiation observed in this pathway.

It was attempted to preserve the water distribution in central nervous tissue by rapid freezing followed by substitution fixation at low temperature.

A method for rapid freezing is described in which use is made of the good heat conducting properties of silver. The freezing was accomplished by bringing the tissue in contact with a polished silver surface at the temperature of liquid nitrogen either at atmospheric or reduced pressure. Helium gas flowing over this surface prevented the condensation of water or air on the silver. After freezing the tissue was placed in a substituting solvent. The best results were obtained with 2% osmium tetroxide in acetone at -85°C. The ultrastructure of the tissue was well preserved in a narrow surface layer only.

DURING spreading depression (SD) the cortex passes through a cycle of major changes. The spontaneous electrical activity becomes deeply depressed, and the potentials evoked by sensory and electrical stimulation of the cortex are greatly reduced ( LEAo. 1944; MARSHALL, 1950; OCHS, 1958). Spreading depression is accompanied by a slow potential change usually consisting of a negative variation followed by positivity of the cortical surface with respect to an indifferent electrode (LEAO, 1947(LEAO, , 1951 ; MARSHALL, ESSIG and DUBROFF, 1951 ; VAN HARREVELD and STAMM, 1951 ; B U R E~, 1954). The electrical resistance of the cortex increases markedly (LEAo and FERREIRA, 1953; FREYGANC and LANDAU, 1955; VAN HARREVELD and OCHS, 1957). A swelling of the apical dendrites by the uptake of water (and ions) from the intercellular spaces can be demonstrated ( VAN HARREVELD, 1958).Changes which are similar to those observed during SD develop with a latency of several minutes after circulatory arrest. The cortical surface becomes negative with respect to an indifferent electrode (LEAo, 1947(LEAo, , 1951 VAN HARREVELD and STAMM, 1953). The time course of this potential is reminiscent of that of the slow potential change accompanying S D . Simultaneously the cortical resistance increases very markedly (VAN HARREVELD and OCHS, 1956) and a swelling of perikarya and apical dendrites takes place (VAN HARREVELD, 1957).The neuronal changes during SD and after circulatory arrest seem to involve a large portion, if not all of the cortical neuronal elements. Such widespread changes may be caused by the release of a compound which then should be present in the cortex a few minutes after stopping the blood flow. To search for such compounds, extracts were prepared of cortex collected about 5 min after circulatory arrest. These extracts as such, and after purification, caused SD when applied to the cerebral cortex. The effects of cortical extracts on a number of other physiological preparations were investigated. The application of extracts in relatively high dilutions caused contraction of crustacean muscle. This preparation proved to be very convenient for the assay of the physiological activity of cortical extracts. Its usefulness was enhanced by the finding that SO many of the properties of the compound eliciting contractions in crustacean muscle parallel those of the substance causing SD that it was probable that an identical compound was involved in both activities. The present paper deals with the identification of this compound.The dorsal aspect of one hemisphere in young adult rabbits was exposed under ether narcosis. During the recording of the electrocorticogram the preparation was immobilized with Squibb's intocostrin (5 to 10 units/kg) and ventilated with a Palmer pump. Usually two pairs of electrodes were placed on the convexity of the hemisphere. The electrocorticogram was recorded with an Offner electroencephalograph. The test solutions were applied for a standard time of 2 min on small cotton pledgets which were placed cl...