Discharge and Role of GABA Pontomesencephalic Neurons in Cortical Activity and Sleep-Wake States Examined by Optogenetics and Juxtacellular Recordings in Mice.

The cholinergic neurons in the pontomesencephalic tegmentum have been shown to discharge in association with and promote cortical activation during active or attentive waking and paradoxical or rapid eye movement sleep. However, GABA neurons lie intermingled with the cholinergic neurons and may contribute to or oppose this activity and role. Here we investigated and the properties, activities, and role of GABA neurons within the laterodorsal tegmental and sublaterodorsal tegmental nuclei (LDT/SubLDT) using male and female transgenic mice expressing channelrhodopsin-()- in vesicular GABA transporter ()-expressing neurons.

Discharge and Role of Acetylcholine Pontomesencephalic Neurons in Cortical Activity and Sleep-Wake States Examined by Optogenetics and Juxtacellular Recording in Mice.

Acetylcholine (ACh) neurons in the pontomesencephalic tegmentum (PMT) are thought to play an important role in promoting cortical activation with waking (W) and paradoxical sleep [PS; or rapid eye movement (REM)], but have yet to be proven to do so by selective stimulation and simultaneous recording of identified ACh neurons. Here, we employed optogenetics combined with juxtacellular recording and labeling of neurons in transgenic (TG) mice expressing ChR2 in choline acetyltransferase (ChAT)-synthesizing neurons. We established then in anesthetized (A) and unanesthetized (UA), head-fixed mice that photostimulation elicited a spike with short latency in neurons which could be identified by immunohistochemical staining as ACh neurons within the laterodorsal (LDT)/sublaterodorsal (SubLDT) and pedunculopontine tegmental (PPT) nuclei.

Homeostatic Changes in GABA and Glutamate Receptors on Excitatory Cortical Neurons during Sleep Deprivation and Recovery.

Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation.

Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes.

Unlabelled: Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone cannot be maintained and narcolepsy with cataplexy ensues. Whether Orx neurons discharge during waking in association with particular conditions, notably with appetitive versus aversive stimuli or positive versus negative emotions, is debated and considered important in understanding their role in supporting particular waking behaviors. Here, we used the technique of juxtacellular recording and labeling in head-fixed rats to characterize the discharge of Orx neurons during the performance of an associative discrimination task with auditory cues for appetitive versus aversive outcomes.

Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat.

Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping-waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep-wake states, cortical activity, and muscle tone.

Muscarinic-2 and orexin-2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep-wake state control.

Acetylcholine (ACh) plays an important role in the promotion of paradoxical sleep (PS) with muscle atonia through the muscarinic-2 receptor (M2R) in the mesopontine tegmentum. Conversely, orexin (Orx or hypocretin) appears to be critical for the maintenance of waking with muscle tone through the orexin-2 (or hypocretin-B) receptor (Orx2R), which is lacking in dogs having narcolepsy with cataplexy. In dual-immunostained material viewed under fluorescence microscopy, we examined the presence and distribution of M2R or Orx2R labeling on all neuronal nuclei (NeuN)-stained neurons or on glutamic acid decarboxylase (GAD)-stained neurons through the mesopontine tegmentum.

Dynamic changes in GABAA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery.

Background: The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABAA receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABAARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep.

Orexin and MCH neurons express c-Fos differently after sleep deprivation vs. recovery and bear different adrenergic receptors.

Though overlapping in distribution within the posterior hypothalamus, neurons containing orexin (Orx) and melanin concentrating hormone (MCH) may play different roles in the regulation of behavioural state. In the present study in rats, we tested whether they express c-Fos differently after total sleep deprivation (SD) vs. sleep recovery (SR).

Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat.

The basal forebrain (BF) plays an important role in modulating cortical activity and facilitating processes of attention, learning, and memory. This role is subserved by cholinergic neurons but also requires the participation of other noncholinergic neurons. Noncholinergic neurons include gamma-amino butyric acidergic (GABAergic) neurons, some of which project in parallel with the cholinergic cells to the cerebral cortex, others of which project caudally or locally.

c-Fos expression in dopaminergic and GABAergic neurons of the ventral mesencephalic tegmentum after paradoxical sleep deprivation and recovery.

Evidence suggests that dopaminergic neurons of the ventral mesencephalic tegmentum (VMT) could be important for paradoxical sleep (PS). Here, we examined whether dopamine (DA) and adjacent gamma-aminobutyric acid (GABA)-synthesizing neurons are active in association with PS recovery as compared to PS deprivation or control conditions in different groups of rats by using c-Fos expression as a reflection of neural activity, combined with dual immunostaining for tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD). Numbers of TH+/c-Fos+ neurons in the substantia nigra (SN) were not significantly different across groups, whereas those in the ventral tegmental area (VTA) were significantly different and greatest in PS recovery.