GABA release in posterior hypothalamus across sleep-wake cycle - PubMed (original) (raw)

GABA release in posterior hypothalamus across sleep-wake cycle

D Nitz et al. Am J Physiol. 1996 Dec.

Abstract

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.

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Figures

Fig. 1.

Summary of histologically verified posterior hypothalamic microdialysis and microinjection sites. Black bars represent the placement of microdialysis probe membrane in each of the experiments. Black circles represent muscimol microinjection sites. Black bars with black circles represent sites used in both microdialysis and microinjection studies. Photomicrograph (×20) corresponds to leftmost microinjection-microdialysis site depicted in schematic at anterior-posterior level (A) 10.5. White arrows in photomicrograph define area of microinjection. Black arrows define track left by microdialysis probe. Dm, dorsomedial nucleus; fd, descending column of the fornix; Hda, dorsal hypothalamic area; Hla, lateral hypothalamic area; Hpa, posterior hypothalamic area; In, infundibular nucleus; mt, mamillothalamic tract; ot, optic tract; tm, tuberomamillary nucleus; Vem, ventromedial nucleus.

Fig. 2.

γ-Aminobutyric acid (GABA) release as a function of sleep-wake state. Average GABA concentrations in microdialysis samples collected in slow-wave sleep (SWS), rapid eye movement (REM) sleep, and wake. Error bars indicate SE; n = 17 for SWS, REM, and wake. *P < 0.05 analysis of variance with Newman-Keuls post hoc _t_-tests.

Fig. 3.

High-performance liquid chromatography and electrochemical detection analysis of GABA release. A: GABA peaks in microdialysis samples from a typical sleep-wake cycle. In each case, peak corresponding to GABA has been blackened. Note increase in height of GABA peak in SWS sample. B: analysis of test microdialysis sample collected from same microdialysis site as in A. Sample was spiked with 100 fmol of GABA to verify identification of GABA peak. QW, quiet waking; AW, active waking.

Fig. 4.

GABA content in microdialysis samples collected from a single microdialysis site over the course of 2 consecutive sleep-wake cycles.

Fig. 5.

Effects of muscimol microinjection on sleep. Total time spent in SWS, REM sleep, and wake in 6 h after sham (open bars), vehicle control (hatched bars), and muscimol (filled bars) injections in posterior hypothalamus. Error bars indicate SE; n = 6 for each condition. **P < 0.01.

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GABA release in posterior hypothalamus across sleep-wake cycle - PubMed (original) (raw)