Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. (1/1840)

In a slice preparation of rat visual cortex, we discovered that paired-pulse stimulation (PPS) elicits a form of homosynaptic long-term depression (LTD) in the superficial layers when carbachol (CCh) or norepinephrine (NE) is applied concurrently. PPS by itself, or CCh and NE in the absence of synaptic stimulation, produced no lasting change. The LTD induced by PPS in the presence of NE or CCh is of comparable magnitude with that obtained with prolonged low-frequency stimulation (LFS) but requires far fewer stimulation pulses (40 vs 900). The cholinergic facilitation of LTD was blocked by atropine and pirenzepine, suggesting involvement of M1 receptors. The noradrenergic facilitation of LTD was blocked by urapidil and was mimicked by methoxamine, suggesting involvement of alpha1 receptors. beta receptor agonists and antagonists were without effect. Induction of LTD by PPS was inhibited by NMDA receptor blockers (completely in the case of NE; partially in the case of CCh), suggesting that one action of the modulators is to control the gain of NMDA receptor-dependent homosynaptic LTD in visual cortex. We propose that this is a mechanism by which cholinergic and noradrenergic inputs to the neocortex modulate naturally occurring receptive field plasticity.  (+info)

NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling. (2/1840)

Single-electrode voltage-clamp techniques and bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30-35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor-dependent component of the perforant path-evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path-evoked current was increased by 63-111% at a holding potential of -30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5-3 mo after the last of 3 or 90-120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control values during a time course of 2.5-3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor-dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling.  (+info)

Long-term effects of prior heat shock on neuronal potassium currents recorded in a novel insect ganglion slice preparation. (3/1840)

Brief exposure to high temperatures (heat shock) induces long-lasting adaptive changes in the molecular biology of protein interactions and behavior of poikilotherms. However, little is known about heat shock effects on neuronal properties. To investigate how heat shock affects neuronal properties we developed an insect ganglion slice from locusts. The functional integrity of neuronal circuits in slices was demonstrated by recordings from rhythmically active respiratory neurons and by the ability to induce rhythmic population activity with octopamine. Under these "functional" in vitro conditions we recorded outward potassium currents from neurons of the ventral midline of the A1 metathoracic neuromere. In control neurons, voltage steps to 40 mV from a holding potential of -60 mV evoked in control neurons potassium currents with a peak current of 10.0 +/- 2.5 nA and a large steady state current of 8.5 +/- 2.6 nA, which was still activated from a holding potential of -40 mV. After heat shock most of the outward current inactivated rapidly (peak amplitude: 8.4 +/- 2.4 nA; steady state: 3.6 +/- 2.0 nA). This current was inactivated at a holding potential of -40 mV. The response to temperature changes was also significantly different. After changing the temperature from 38 to 42 degrees C the amplitude of the peak and steady-state current was significantly lower in neurons obtained from heat-shocked animals than those obtained from controls. Our study indicates that not only heat shock can alter neuronal properties, but also that it is possible to investigate ion currents in insect ganglion slices.  (+info)

Molecular studies suggest that cartilaginous fishes have a terminal position in the piscine tree. (4/1840)

The Chondrichthyes (cartilaginous fishes) are commonly accepted as being sister group to the other extant Gnathostomata (jawed vertebrates). To clarify gnathostome relationships and to aid in resolving and dating the major piscine divergences, we have sequenced the complete mtDNA of the starry skate and have included it in phylogenetic analysis along with three squalomorph chondrichthyans-the common dogfish, the spiny dogfish, and the star spotted dogfish-and a number of bony fishes and amniotes. The direction of evolution within the gnathostome tree was established by rooting it with the most closely related non-gnathostome outgroup, the sea lamprey, as well as with some more distantly related taxa. The analyses placed the chondrichthyans in a terminal position in the piscine tree. These findings, which also suggest that the origin of the amniote lineage is older than the age of the oldest extant bony fishes (the lungfishes), challenge the evolutionary direction of several morphological characters that have been used in reconstructing gnathostome relationships. Applying as a calibration point the age of the oldest lungfish fossils, 400 million years, the molecular estimate placed the squalomorph/batomorph divergence at approximately 190 million years before present. This dating is consistent with the occurrence of the earliest batomorph (skates and rays) fossils in the paleontological record. The split between gnathostome fishes and the amniote lineage was dated at approximately 420 million years before present.  (+info)

Distribution of haplotypes from a chromosome 21 region distinguishes multiple prehistoric human migrations. (5/1840)

Despite mounting genetic evidence implicating a recent origin of modern humans, the elucidation of early migratory gene-flow episodes remains incomplete. Geographic distribution of haplotypes may show traces of ancestral migrations. However, such evolutionary signatures can be erased easily by recombination and mutational perturbations. A 565-bp chromosome 21 region near the MX1 gene, which contains nine sites frequently polymorphic in human populations, has been found. It is unaffected by recombination and recurrent mutation and thus reflects only migratory history, genetic drift, and possibly selection. Geographic distribution of contemporary haplotypes implies distinctive prehistoric human migrations: one to Oceania, one to Asia and subsequently to America, and a third one predominantly to Europe. The findings with chromosome 21 are confirmed by independent evidence from a Y chromosome phylogeny. Loci of this type will help to decipher the evolutionary history of modern humans.  (+info)

Genomic evolution during a 10,000-generation experiment with bacteria. (6/1840)

Molecular methods are used widely to measure genetic diversity within populations and determine relationships among species. However, it is difficult to observe genomic evolution in action because these dynamics are too slow in most organisms. To overcome this limitation, we sampled genomes from populations of Escherichia coli evolving in the laboratory for 10,000 generations. We analyzed the genomes for restriction fragment length polymorphisms (RFLP) using seven insertion sequences (IS) as probes; most polymorphisms detected by this approach reflect rearrangements (including transpositions) rather than point mutations. The evolving genomes became increasingly different from their ancestor over time. Moreover, tremendous diversity accumulated within each population, such that almost every individual had a different genetic fingerprint after 10,000 generations. As has been often suggested, but not previously shown by experiment, the rates of phenotypic and genomic change were discordant, both across replicate populations and over time within a population. Certain pivotal mutations were shared by all descendants in a population, and these are candidates for beneficial mutations, which are rare and difficult to find. More generally, these data show that the genome is highly dynamic even over a time scale that is, from an evolutionary perspective, very brief.  (+info)

Screening for breast cancer: time, travel, and out-of-pocket expenses. (7/1840)

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P < .001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P < .001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.  (+info)

Toward a utility theory foundation for health status index models. (8/1840)

The axioms of utility theory are restated in terms of health outcomes, and some additional assumptions, consistent with the assumptions implicit in health status index models, are adduced to develop a consistent theory of the utility of health states. On the basis of the axioms and specific assumptions, techniques for measuring the health utility functions of individuals are described, and it is shown how these axioms and assumptions may be used to determine the utility to the individual of health programs that will affect him in various ways.  (+info)