Ca2+-permeable AMPA receptors mediate induction of test pulse depression of naive synapses in rat visual cortical slices at early postnatal stage.

Synaptic depression in the hippocampus at early postnatal stage can be induced by test pulse stimulation (<1 Hz). However, the receptor mechanism for induction of this synaptic depression is unclear. In the present study, we used whole-cell patch clamp recording in vitro to investigate how excitatory and inhibitory synapses onto layer II/III pyramidal neurons of the primary visual cortex adapt to test pulse activation from a previously non-activated (naive) state. We found that excitatory postsynaptic currents (EPSCs) of pyramidal neurons were rapidly depressed by 0.1 Hz stimulation in acutely prepared slices from rats at 11-12 postnatal days, while this phenomena disappeared in slices from young adolescent rats (23-24 postnatal days). By contrast, inhibitory postsynaptic currents (IPSCs) were relatively stable following 0.1 Hz stimulation of rat slices at the same early postnatal stage. Moreover, the test pulse depression of EPSCs was associated with a decrease in 1/coefficient of variation (CV)(2) and no change in the paired-pulse ratio. These data imply silencing of synapses and no significant change either in postsynaptic receptor density or presynaptic terminal release probability. This synaptic depression was unaffected by the competitive NMDA receptor antagonist D-APV. Ca(2+)-permeable AMPA receptor selective antagonists, Naspm or IEM-1460, prevented the induction of the test pulse depression. These data suggest that EPSCs, but not IPSCs, were rapidly depressed by test pulse stimulation in rats at early postnatal stage via a Ca(2+)-permeable AMPA receptor-dependent mechanism.

Prenatal exposure to heroin in mice elicits memory deficits that can be attributed to neuronal apoptosis.

Maternal heroin abuse has been shown to result in teratogenic neurobehavioral defects in the offspring, but the underlying mechanisms remain largely unknown. This study was designed to explore the role of neuronal apoptosis in the heroin-induced neurobehavioral defects of learning and memory. Pregnant BALB/c mice were treated with either heroin or saline. The animals in the heroin group received heroin subcutaneously at a dosage of 10 mg/kg/day on embryonic days (E) 9-18, while those in the saline group were treated as drug-naive. Offspring were grouped as prenatal heroin exposure (HER), prenatal saline exposure (SAL), and control (CON) groups, according to the maternal treatment regimen. Some of the mice were killed and their hippocampus harvested on postnatal day (P) 14, and the tissue subjected to reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry to reveal the mRNA and protein expressions of caspase-3, Bcl-2, and Bax. The Morris water maze was applied to assess the learning and memory capability of the mice at P30; poor maze performances were observed for the animals in the HER group. The results also showed that the mRNA and protein expressions of caspase-3 and Bax were significantly increased, while that of Bcl-2 was markedly decreased in the HER group compared with both the SAL and CON groups. The immunohistochemistry revealed significant caspase-3 immunoreactivity in the dentate gyrus and cornu ammonis (CA) 1 subareas of the hippocampal formation, whereas, no significant changes were seen in subarea CA3. These findings suggest that prenatal heroin exposure during the E9-18 period enhances neuronal apoptosis by altering the expressions of caspase-3, Bcl-2, and Bax in the mouse hippocampus, and leads to impairment in hippocampus-dependent learning and memory.

[A quantitative study on the synaptic ultrastructural alterations in visual cortex in the maintenance of LTP].

The ultrastructure of synapses three hours after formation of long-term potentiation (LTP) was examined in the local microslices of visual cortical brain slices of 18-20 d rats. Slices without potentiating stimulation which were similarly incubated served as controls. The following structural changes were examined using a graph analyzer: (1) synaptic cleft width; (2) thickness of the postsynaptic densities(PSD); (3) length of the active zones; and (4) curvature of the synaptic interface. The number of synapses of different types in layer II/III of visual cortex was quantified by double-blind scoring procedures. The various counts were converted to the number of synapses per unit volume using stereological quantitation method. Analysis of variance was used for statistical evaluation. Our results suggest that field potentials reached their peak values at about one and a half hours after tetanus and could be maintained as long as three hours without decay. In comparison with the control groups, synaptic cleft width, thickness of PSD, surface density per unit volume(Sv) of the active zones, curvature of the synaptic interface, numeric density per unit volume (Nv) of all synapses, spine synapses and the Nv of perforated synapses were all increased significantly. These data suggest that the increase of Sv of active zones and the increase of the curvature of synaptic interface may be the morphological feature characterizing the maintenance of LTP, in addition to the formation of perforated synapses.

Induction of LTP in rat primary visual cortex: tetanus parameters.

Long-term potentiation (LTP), intensively studied in the hippocampus as a possible mnemonic device, has begun to be studied in the neocortex. In this study the effects of varying tetanic stimulus parameters on LTP of field potentials recorded from layer II/III induced by white matter stimulation in the in vitro rat visual cortical slice were examined. Low intensity tetanus was more effective in producing LTP than high-intensity tetanus, although single pulses of very high intensity reliably resulted in LTP. LTP consistently occurred following 2 Hz-60 min, or 100 Hz-10 min tetanus; whereas, 10 min of 7 and 25 Hz tetanus usually resulted in long-lasting depression. Although no obvious rule related tetanus frequency and duration to the incidence of LTP, an inverted-U relationship was found between tetanus frequency and LTP magnitude.

[A retrospective study of 115 cases of fungal pneumonia].

115 cases of immunocompromised patients complicated with fungal pneumonia treated during the period from April 1968 to December 1986 were retrospectively studied. 96 were male and 19 female. Their age ranged from 6 to 84. The incidence increased significantly in recent years especially after 1983. Severe liver disease was the underlying disease in 102 (88.7%) patients. 108 (93.9%) had received antibiotics and 55 (47.9%) corticosteroids. Fungi species isolated were candida in 107 (54.9%), aspergillus in 82 (36.9%), penicillium in 7 (3.6%), mucormycetes in 6 (3%) and reotrichum in 3 (1.5%). Fever, cough, expectoration, moist rales diminished breath sounds and increase of W. B. C. and neutrophils were the important clinical features. The roentgenologic findings vary with the nature and extent of the pathologic process. Disseminated mycoses were found in 9 of the 18 autopsied cases. The characteristic pathologic findings were inflammation, abscess formation, vasculitis, infarction and hemorrhage. Extrapulmonary features such as enteritis, purulent nephritis, abnormal EKG, encephalopathy and rash were present. 93 cases received antifungal therapy including garlicin, clotrimazole, amphotericin B, nystatine, miconazole, 5-fluctosine and ketoconazole. Because these drug combinations were so complex, it is difficult to evaluate their efficiency. However the survival rate was somewhat elevated in recent years. The mortality rate of this series was 80.9%.