Wakefulness Is Governed by GABA and Histamine Cotransmission

Yu, Xiao; Z, Ye; Houston, Catriona M.; Zecharia, Anna; Ma, Ying; Zhang, Zhe; Uygun, David S.; Parker, Susan; Vyssotski, Alexei L.; Yustos, Raquel; Franks, Nicholas P.; Brickley, Stephen G.; Wisden, William

doi:10.1016/j.neuron.2015.06.003

Cited by 146 publications

(175 citation statements)

References 72 publications

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“…Increase of extracellular GABA may increase tonic inhibition but not necessarily be associated with increase of the phasic GABA release. Further, several studies revealed co-release of GABA with ACh and HA (Saunders et al, 2015; Yu et al, 2015) which suggests a decrease of GABA during NREM sleep while the observations from microdialysis experiments (Vanini et al, 2012) suggest an increase of GABA during NREM sleep. Therefore, in our study, we also tested models with (a) no change in the level of the GABA release; (b) increase of tonic inhibition reflecting increase of the extracellular GABA, based on the observations from microdialysis experiments (Vanini et al, 2012); and (c) tonic inhibition proportional to the ACh and HA levels, based on the evidence of the co-release of GABA with ACh (Saunders et al, 2015) and HA (Yu et al, 2015).…”

Section: Resultsmentioning

confidence: 98%

Cellular and neurochemical basis of sleep stages in the thalamocortical network

Krishnan

Chauvette

Shamie

et al. 2016

eLife

116

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The link between the combined action of neuromodulators in the brain and global brain states remains a mystery. In this study, using biophysically realistic models of the thalamocortical network, we identified the critical intrinsic and synaptic mechanisms, associated with the putative action of acetylcholine (ACh), GABA and monoamines, which lead to transitions between primary brain vigilance states (waking, non-rapid eye movement sleep [NREM] and REM sleep) within an ultradian cycle. Using ECoG recordings from humans and LFP recordings from cats and mice, we found that during NREM sleep the power of spindle and delta oscillations is negatively correlated in humans and positively correlated in animal recordings. We explained this discrepancy by the differences in the relative level of ACh. Overall, our study revealed the critical intrinsic and synaptic mechanisms through which different neuromodulators acting in combination result in characteristic brain EEG rhythms and transitions between sleep stages.DOI: http://dx.doi.org/10.7554/eLife.18607.001

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Section: Resultsmentioning

confidence: 98%

Cellular and neurochemical basis of sleep stages in the thalamocortical network

Krishnan

Chauvette

Shamie

et al. 2016

eLife

116

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“…The absence of other neuromodulators could also contribute, such as orexin or histamine [30]. However, orexinergic and histaminergic projections mainly target deep layers and at least for orexin, post-synaptic signaling seems to be confined to layer 6 [31, 32]. Thalamic mechanisms could also play a role, since relay thalamic nuclei provide the main input to layer 4 in primary areas.…”

Section: Resultsmentioning

confidence: 99%

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

et al. 2016

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Summary Sleep is traditionally constituted of two global behavioral states, NREM and REM, characterized by quiescence and reduced responsiveness to sensory stimuli [1]. NREM sleep is distinguished by slow waves and spindles throughout the cerebral cortex, REM sleep by an ‘activated’, low-voltage fast EEG paradoxically similar to that of wake, accompanied by rapid eye movements and muscle atonia. However, recent evidence has shown that cortical activity patterns during wake and NREM sleep are not as global as previously thought. Local slow waves can appear in various cortical regions in both awake humans [2] and rodents [3-5]. Intracranial recordings in humans [6] and rodents [4, 7] have shown that NREM sleep slow waves most often involve only a subset of brain regions that varies from wave to wave rather than occurring near-synchronously across all cortical areas. Moreover, some cortical areas can transiently ‘wake up’ [8] in an otherwise sleeping brain. Yet, until now, cortical activity during REM sleep was thought to be homogenously wake-like. We show here, using local laminar recordings in freely moving mice, that slow waves occur regularly during REM sleep, but only in primary sensory and motor areas, and mostly in layer 4, the main target of relay thalamic inputs, and in layer 3. This finding may help explain why during REM sleep we remain disconnected from the environment even though the bulk of the cortex shows wakelike, paradoxical activation.

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“…In addition, there is evidence for GABA and DA co-transmission in by substantia nigra pars compacta neurons as well as retinal amacrine neurons (Tritsch et al 2012; Hirasawa et al, 2012). Other forms of neurotransmission include GABA and histamine by hypothalamic neurons (Yu et al, 2015), glutamate and acetylcholine co-transmission in striatal interneurons or medial habenula neurons (Gras et al, 2008; Ren et al, 2011; Higley et al, 2011; Nelson et al, 2014), GABA and acetylcholine co-transmission in corticopetal globus pallidus neurons (Saunders et al, 2015). …”

Section: Cellular Diversity In the Ventral Tegmental Areamentioning

confidence: 99%

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

Barker

Root

Zhang

et al. 2016

Journal of Chemical Neuroanatomy

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The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in ‘multiplexed’ neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression.

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Wakefulness Is Governed by GABA and Histamine Cotransmission

Cited by 146 publications

References 72 publications

Cellular and neurochemical basis of sleep stages in the thalamocortical network

Cellular and neurochemical basis of sleep stages in the thalamocortical network

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

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