Nuclear electric quadrupole moments of Rb from the hyperfine spectrum of RbF.

The molecular beam electric resonance technique has been used to examine the hyperfine spectrum of RbF. The Rb nuclear electric quadrupole interaction, the spin-rotation interactions, and tensor and scalar spin-spin interactions have been measured for both Rb isotopes, including their dependence on vibrational and rotational states. Transition frequencies have been determined to a precision of better than 1 Hz in many cases. The magnetic interactions in the two isotopomers are consistent with what is expected from the known masses and magnetic dipole moments. In the case of the Rb nuclear electric quadrupole interaction, adjustments have been made for a small isotopomer shift, and for the ratio of the effective nuclear electric quadrupole moments, Q(87Rb)Q(85Rb) = 0.483 830 1+/-0.000 001 8. The effective quadrupole interaction includes a pseudoquadrupole interaction that may be significant at this level of precision, but cannot be distinguished experimentally.

An anomaly in the isotopomer shift of the hyperfine spectrum of LiI.

A high-precision examination of the hyperfine spectrum of 6LiI in comparison with 7LiI shows a shift in the iodine nuclear electric quadrupole moment that cannot be accounted for by a model in which the electric field gradient at the iodine site is assumed to depend only upon the internuclear distance between Li and I. The other hyperfine interactions are consistent between the two isotopomers, including the previously reported electric hexadecapole interaction of the iodine nucleus.

Uncoupling of brain activity from movement defines arousal States in Drosophila.

BACKGROUND: An animal's state of arousal is fundamental to all of its behavior. Arousal is generally ascertained by measures of movement complemented by brain activity recordings, which can provide signatures independently of movement activity. Here we examine the relationships among movement, arousal state, and local field potential (LFP) activity in the Drosophila brain. RESULTS: We have measured the correlation between local field potentials (LFPs) in the brain and overt movements of the fruit fly during different states of arousal, such as spontaneous daytime waking movement, visual arousal, spontaneous night-time movement, and stimulus-induced movement. We found that the correlation strength between brain LFP activity and movement was dependent on behavioral state and, to some extent, on LFP frequency range. Brain activity and movement were uncoupled during the presentation of visual stimuli and also in the course of overnight experiments in the dark. Epochs of low correlation or uncoupling were predictive of increased arousal thresholds even in moving flies and thus define a distinct state of arousal intermediate between sleep and waking in the fruit fly. CONCLUSIONS: These experiments indicate that the relationship between brain LFPs and movement in the fruit fly is dynamic and that the degree of coupling between these two measures of activity defines distinct states of arousal.

Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep.

The idea that sleep could serve a cognitive function has remained popular since Freud stated that dreams were "not nonsense" but a time to sort out experiences [S. Freud, Letter to Wilhelm Fliess, May 1897, in The Origins of Psychoanalysis - Personal Letters of Sigmund Freud, M. Bonaparte, A. Freud, E. Kris (Eds.), Translated by E. Mosbacher, J. Strachey, Basic Books and Imago Publishing, 1954]. Rapid eye movement (REM) sleep, which is associated with dream reports, is now known to be is important for acquisition of some tasks [A. Karni, D. Tanne, B.S. Rubenstein, J.J.M. Askenasy, D. Sagi, Dependence on REM sleep of overnight improvement of a perceptual skill, Science 265 (1994) 679-682; C. Smith, Sleep states and learning: a review of the animal literature, Biobehav. Rev. 9 (1985) 157-168]; although why this is so remains obscure. It has been proposed that memories may be consolidated during REM sleep or that forgetting of unnecessary material occurs in this state [F. Crick, G. Mitchison, The function of dream sleep, Nature 304 (1983) 111-114; D. Marr, Simple memory: a theory for archicortex, Philos. Trans. R. Soc. B. 262 (1971) 23-81]. We studied the firing of multiple single neurons in the hippocampus, a structure that is important for episodic memory, during familiar and novel experiences and in subsequent REM sleep. Cells active in familiar places during waking exhibited a reversal of firing phase relative to local theta oscillations in REM sleep. Because firing-phase can influence whether synapses are strengthened or weakened [C. Holscher, R. Anwyl, M.J. Rowan, Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo, J. Neurosci. 15 (1977) 6470-6477; P.T. Huerta, J.E. Lisman, Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro, Neuron 15 (1995) 1053-1063; C. Pavlides, Y.J. Greenstein, M. Grudman, J. Winson, Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm, Brain Res. 439 (1988) 383-387] this experience-dependent phase shift, which developed progressively over multiple sessions in the environment, is consistent with the hypothesis that circuits may be restructured during REM sleep by selectively strengthening recently acquired memories and weakening older ones.

Hippocampal EEG and unit activity responses to modulation of serotonergic median raphe neurons in the freely behaving rat.

Hippocampal EEG, GABAergic interneurons, and principal cells were recorded simultaneously as rats foraged within one of three environments both before and after modulation of serotonergic inputs to the hippocampus. Median raphe microinjections of the 5-HT1a receptor agonist 8-OH-DPAT were made to produce inhibition of serotonergic neurons in this region. Such microinjections produced behavioral arousal and increases in the amplitude of hippocampal EEG theta. Consistent with the pattern of serotonergic innervation of the hippocampus, the GABAergic interneuron population was affected differentially by the microinjections. Principal cells were generally unaffected by the manipulation and maintained robust spatial firing correlates within the foraging environment. The results provide basic data on the relationship between serotonergic median raphe neurons and hippocampal activity in a behaving animal. The data suggest that behavioral responses to manipulation of the serotonergic system are mediated by brain regions other than the hippocampus or are mediated through changes in the activity of hippocampal interneurons.

GABA release in the dorsal raphe nucleus: role in the control of REM sleep.

The cessation of firing of serotonergic dorsal raphe neurons is a key controlling event of rapid eye movement (REM) sleep. We tested the hypothesis that this cessation of activity is due to gamma-aminobutyric acid (GABA) release using the in vivo microdialysis technique. We found that REM sleep is accompanied by a selective increase in GABA release, but not by a change in glutamate or glycine release in the dorsal raphe nucleus. Microinjection of the GABA agonist muscimol into the dorsal raphe increased REM sleep, although microperfusion of the GABA antagonist picrotoxin blocked REM sleep. These results implicate GABA release as a critical element in the production of the REM sleep state and in the control of discharge in serotonergic neurons across the sleep/wake cycle.

GABA release in the locus coeruleus as a function of sleep/wake state.

GABA, glutamate, and glycine release in the locus coeruleus were measured as a function of sleep/wake state in the freely-behaving cat using the microdialysis technique. GABA release was found to increase during rapid-eye-movement sleep as compared to waking values. GABA release during slow-wave sleep was intermediate between that of waking states and rapid-eye-movement sleep. The concentration of glutamate and glycine in microdialysis samples was unchanged across sleep and wake states. Our findings are consistent with the hypothesis that GABAergic inhibition is responsible for the cessation of discharge in locus coeruleus neurons during REM sleep. The data suggest that a population of GABAergic neurons innervating the locus coeruleus are selectively active during rapid-eye-movement sleep.

GABA release in posterior hypothalamus across sleep-wake cycle.

The activity of neurons in the posterior hypothalamus (PH) is thought to contribute to the production of wakefulness and electroencephalograph desynchronization. Inactivation of neuronal activity in this area is known to induce sleep. Most PH neurons decrease unit discharge during slow-wave sleep (SWS) relative to wake and rapid eye movement sleep. In the present study, we sought to examine potential sources of inhibition or disfacilitation underlying the reduction of PH unit activity during SWS in the cat. We employed the microdialysis technique in conjunction with high-performance liquid chromatography methods for the quantification of glutamate, glycine, and gamma-aminobutyric acid (GABA) release. We found a selective increase in GABA release during SWS in the PH. Glutamate and glycine levels were unchanged across the sleep-wake cycle. microinjection of the GABAA-receptor agonist muscimol, into the same areas from which microdialysis samples were collected, increased SWS time. Our studies support the hypothesis that GABA release in the posterior hypothalamus mediates inhibition of posterior hypothalamic neurons, thereby facilitating SWS.

Concurrent reflectance imaging and microdialysis in the freely behaving cat.

We present a method to perform simultaneous microdialysis with light reflectance imaging of neural activity in a discrete brain region of the freely behaving animal. We applied this method to the dorsal hippocampus of freely behaving cats to (1) measure extracellular glutamate and reflectance variations across a sleep-waking cycle, (2) assess spatially coherent neural activity changes accompanying local perfusion of cocaine and (3) measure local changes in cell volume induced by infusion of hyper- and hypo-osmotic solutions. Higher extracellular glutamate concentrations corresponded to higher imaged neural activity. Sequential images showed that cocaine perfusion elicited a propagating reflectance change as cocaine reached the tissue. Microperfusion of hypo-osmotic solution ( - 100 mOsm), which increases cell volume, decreased reflectance. Microperfusion of hyperosmotic sucrose solutions, which reduce cell volume, increased reflectance in a dose-dependent manner. The data indicate that reflectance imaging can measure changes in cell volume, and could, thus, measure neural activity through activity/cell volume corollaries. Combining microdialysis and optical imaging enables investigation of the neurochemical bases of spontaneous neural activity patterns within discrete brain nuclei.

Altered distribution of cholinergic cells in the narcoleptic dog.

Narcolepsy is characterized by excessive sleepiness and episodes of cataplexy brought on by emotional excitation. Cataplexy and sleep paralysis have been hypothesized to be produced by the triggering during waking of brain stem cholinergic mechanisms normally acting to induce atonia in REM sleep. We hypothesized that narcoleptics have an abnormal number of LDT and/or PPN cholinergic neurons. A comparison was made of cholinergic cell numbers in the brain stems of normal and narcoleptic canines. Cholinergic neurons were identified by NADPH-diaphorase histochemistry. We found increased numbers of cholinergic neurons at the R6-R7 level of the LDT and PPN in narcoleptic canines. This abnormality can explain alterations in cholinergic receptor number, acetylcholine release, and the occurrence of cataplexy and sleep paralysis that characterize narcolepsy.