The role of mesopontine NGF in sleep and wakefulness.

The microinjection of nerve growth factor (NGF) into the cat pontine tegmentum rapidly induces rapid eye movement (REM) sleep. To determine if NGF is involved in naturally-occurring REM sleep, we examined whether it is present in mesopontine cholinergic structures that promote the initiation of REM sleep, and whether the blockade of NGF production in these structures suppresses REM sleep. We found that cholinergic neurons in the cat dorso-lateral mesopontine tegmentum exhibited NGF-like immunoreactivity.

Eszopiclone prevents excitotoxicity and neurodegeneration in the hippocampus induced by experimental apnea.

Study Objective: This study was designed to determine the effects of eszopiclone on apnea-induced excitotoxic synaptic processes and apoptosis in the hippocampus.

Design: Recurrent periods of apnea, which consisted of a sequence of apnea (75% SpO2), followed by ventilation with recovery to normoxia (> 95% SpO2), were induced for a period of three hours in anesthetized guinea pigs. The CA3 Schaffer collateral pathway in the hippocampus was stimulated and the field excitatory postsynaptic potential (fEPSP) response was recorded in CA1.

State-dependent control of lumbar motoneurons by the hypocretinergic system.

Neurons in the lateral hypothalamus (LH) that synthesize hypocretins (Hcrt-1 and Hcrt-2) are active during wakefulness and excite lumbar motoneurons. Because hypocretinergic cells also discharge during phasic periods of rapid eye movement (REM) sleep, we sought to examine their action on the activity of motoneurons during this state. Accordingly, cat lumbar motoneurons were intracellularly recorded, under alpha-chloralose anesthesia, prior to (control) and during the carbachol-induced REM sleep-like atonia (REMc).

Apnea promotes glutamate-induced excitotoxicity in hippocampal neurons.

Patients with obstructive sleep apnea (OSA) exhibit hippocampal damage and cognitive deficits. To determine the effect of apnea on the synaptic transmission in the hippocampus, we performed electrophysiological studies in an in vivo guinea pig model of OSA. Specifically, we determined the cornu ammonis region 1 (CA1) field excitatory postsynaptic potential (fEPSP) response to cornu ammonis region 3 (CA3) stimulation and examined the presynaptic mechanisms underlying the changes in the fEPSP.

The unique inhibitory potentials in motoneurons that occur during active sleep are comprised of minimal unitary potentials.

Loss of muscle tone during active (rapid-eye-movement, REM) sleep is due to the inhibition of motoneurons. This inhibition is manifest in high-gain intracellular electrophysiological records as hyperpolarizing synaptic noise, which includes large amplitude active sleep-specific inhibitory postsynaptic potentials (IPSPs). We report here evidence that the large active sleep-specific IPSPs are comprised of a small number of minimal unitary potentials that are characterized by fast rise-times (10-90% rise-times < or = 0.

Hypocretinergic control of spinal cord motoneurons.

Hypocretinergic (orexinergic) neurons in the lateral hypothalamus project to motor columns in the lumbar spinal cord. Consequently, we sought to determine whether the hypocretinergic system modulates the electrical activity of motoneurons. Using in vivo intracellular recording techniques, we examined the response of spinal motoneurons in the cat to electrical stimulation of the lateral hypothalamus.

Colocalization of gamma-aminobutyric acid and acetylcholine in neurons in the laterodorsal and pedunculopontine tegmental nuclei in the cat: a light and electron microscopic study.

Cholinergic and gamma-aminobutyric acid (GABA) mechanisms in the dorsolateral pontomesencephalic tegmentum have been implicated in the control of active (REM) sleep and wakefulness. To determine the relationships between neurons that contain these neurotransmitters in this region of the brainstem in adult cats, combined light and electron microscopic immunocytochemical procedures were employed. Light microscopic analyses revealed that choline acetyltransferase (ChAT) and GABA immunoreactive neurons were distributed throughout the laterodorsal and pedunculopontine tegmental nuclei (LDT and PPT).

Hypocretinergic facilitation of synaptic activity of neurons in the nucleus pontis oralis of the cat.

The present study was undertaken to explore the neuronal mechanisms of hypocretin actions on neurons in the nucleus pontis oralis (NPO), a nucleus which plays a key role in the generation of active (REM) sleep. Specifically, we sought to determine whether excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the laterodorsal tegmental nucleus (LDT) and spontaneous EPSPs in NPO neurons are modulated by hypocretin. Accordingly, recordings were obtained from NPO neurons in the cat in conjunction with the juxtacellular microinjection of hypocretin-1 onto intracellularly recorded cells.

Hypocretinergic neurons are primarily involved in activation of the somatomotor system.

The hypocretinergic system has been implicated in the generation and/or maintenance of wakefulness. Our results challenge this hypothesis. Utilizing cats as an animal model and immunocytochemical procedures for the simultaneous detection of hypocretin and Fos, we determined that hypocretinergic neurons are activated during wakefulness but only when somatomotor activity is present.

Induction of active (REM) sleep and motor inhibition by hypocretin in the nucleus pontis oralis of the cat.

Hypocretin (orexin)-containing neurons in the hypothalamus, which have been implicated in the pathology of narcolepsy, project to nuclei in the brain stem reticular formation that are involved in the control of the behavioral states of sleep and wakefulness. Among these nuclei is the nucleus pontis oralis (NPO). Consequently, the present study was undertaken to determine if the hypocretinergic system provides regulatory input to neurons in the NPO with respect to the generation of the states of sleep and wakefulness.