Amines, Astrocytes, and Arousal

Bazargani, Narges; Attwell, David

doi:10.1016/j.neuron.2017.03.035

Cited by 31 publications

(20 citation statements)

References 27 publications

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“…Astrocytes can release gliotransmitters including glutamate, GABA, D-serine, and ATP to influence local neurons (46,74). Phenylephrine increased glutamatergic sEPSCs onto vPAG DA neurons, this effect was preserved in the presence of TTX, and CNQX abolished phenylephrine-induced increases in sEPSCs on vPAG DA neurons (Figure 4).…”

Section: α1ars On Vpag Astrocytes Modulate Wakefulnessmentioning

confidence: 97%

Noradrenergic Transmission at Alpha1-Adrenergic Receptors in the Ventral Periaqueductal Gray Modulates Arousal

Porter-Stransky

Centanni

Karne

et al. 2019

Biological Psychiatry

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Background.-Dysregulation of arousal is symptomatic of numerous psychiatric disorders. Previous research has shown that the activity of dopamine (DA) neurons in the ventral periaqueductal gray (vPAG) tracks with arousal state, and lesions of vPAG DA cells increase sleep. However, the circuitry controlling these wake-promoting DA neurons is unknown. Methods.-The present study combines Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), behavioral pharmacology, electrophysiology, and immunoelectron microscopy in male and female mice to elucidate mechanisms in the vPAG that promote arousal. Results.-DREADD-induced activation of locus coeruleus (LC) projections to the vPAG or vPAG DA neurons promoted arousal. Similarly, agonist stimulation of vPAG α1-adrenergic receptors (α1ARs) increased latency to fall asleep, while α1AR blockade had the opposite effect. α1AR stimulation drove vPAG DA activity in a glutamate-dependent, action potential-independent

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Section: α1ars On Vpag Astrocytes Modulate Wakefulnessmentioning

confidence: 97%

Noradrenergic Transmission at Alpha1-Adrenergic Receptors in the Ventral Periaqueductal Gray Modulates Arousal

Porter-Stransky

Centanni

Karne

et al. 2019

Biological Psychiatry

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“…Additionally, the α1bAR was found in glial elements in the NAc core and shell in this study. In other brain regions, it has been shown that NE (under the control of the α1AR) from the LC could cause glutamate release from astrocytes that in turn could affect release of other neurotransmitters, such as dopamine (Mitrano et al, 2016; Bazargani & Attwell, 2017). This also points to NE-DA interactions that need further examination in the NAc, as glial contributions to neurotransmission have become of increasing interest.…”

Section: Discussionmentioning

confidence: 99%

α1b-Adrenergic Receptor Localization and Relationship to the D1-Dopamine Receptor in the Rat Nucleus Accumbens

et al. 2018

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The α1-adrenergic receptors (α1ARs) have been implicated in numerous actions of the brain, including attention and wakefulness. Additionally, they have been identified as contributing to disorders of the brain, such as drug addiction, and recent work has shown a role of these receptors in relapse to psychostimulants. While some functionality is known, the actual subcellular localization of the subtypes of the α1ARs remains to be elucidated. Further, their anatomical relationship to receptors for other neurotransmitters, such as dopamine (DA), remains unclear. Therefore, using immunohistochemistry and electron microscopy techniques, this study describes the subcellular localization of the α1b-adrenergic receptor (α1bAR), the subtype most tied to relapse behaviors, as well as its relationship to the D1-dopamine receptor (D1R) in both the shell and core of the rat nucleus accumbens (NAc). Overall, α1bARs were found in unmyelinated axons and axon terminals with some labeling in dendrites. In accordance with other studies of the striatum, the D1R was found mainly in dendrites and spines; therefore, colocalization of the D1R with the α1bAR was rare postsynaptically. However, in the NAc shell, when the receptors were co-expressed in the same neuronal elements there was a trend for both receptors to be found on the plasma membrane, as opposed to the intracellular compartment. This study provides valuable anatomical information about the α1bAR and its relationship to the D1R and the regulation of DA and norepinephrine (NE) neurotransmission in the brain which have been examined previously.

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“…Besides a2-adrenergic receptors, GIRK channels are known to be activated by mGluR2 receptors (Watanabe and Nakanishi, 2003), A1 adenosine receptors (Kim and Johnston, 2015; X. and purinergic receptors (Erb and Weisman, 2012;Filippov et al, 2004). We tested whether these signaling pathways contributed directly or indirectly (Bazargani and Attwell, 2017) to the NE-mediated GIRK activation in GoCs by bath applying the group II mGluR antagonist LY341495 (100μM; NE: 42 ± 9 pA, NE+LY: 46 ± 3 pA; n = 6; Wilcoxon signed-rank test, p = 0.688; Figure 3H) and a cocktail of the P2Y12 purinergic receptor antagonist PSB 0739 (0.1 mM; (Madry et al, 2018)) and A1 adenosine receptor antagonist DPCPX (100 nM; NE: 23 ± 5 pA, NE+PSB/DPCPX: 26 ± 3 pA; n = 7; Wilcoxon signed-rank test, p = 0.938; Figure 3I).…”

Section: Norepinephrine-mediated Hyperpolarization Is Mediated By Girmentioning

confidence: 99%

“…NE also modulates excitatory synaptic transmission onto Purkinje cells as well as down regulating the induction of synaptic plasticity (Carey and Regehr, 2009). Moreover, enhanced glial cell activity during locomotion is mediated by noradrenergic pathways (Bazargani and Attwell, 2017;Paukert et al, 2014). While noradrenergic inputs are present in all of the layers of the cerebellar cortex (Berger et al, 1979;Olson and Fuxe, 1971), noradrenergic modulation has only been reported in the molecular layer, where most plasticity is thought to occur (Gao et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer

Lanore¹,

Rothman²,

Coyle³

et al. 2019

Preprint

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Golgi cells (GoCs) are the main inhibitory interneurons in the input layer of the cerebellar cortex and are electrically coupled together, forming syncytia. GoCs control the excitability of granule cells (GCs) through feedforward, feedback and spillovermediated inhibition. The GoC circuit therefore plays a central role in determining how sensory and motor information is transformed as it flows through the cerebellar input layer. Recent work has shown that GCs are activated when animals perform active behaviours, but the underlying mechanisms remain poorly understood. Norepinephrine (NE), also known as noradrenaline, is a powerful modulator of network function during active behavioral states and the axons of NE-releasing neurons in the locus coeruleus innervate the cerebellar cortex. Here we show that NE hyperpolarizes the GoC membrane potential, decreases spontaneous firing and reduces the gain of the spike frequency versus input-current relationship. The GoC membrane hyperpolarization can be mimicked with an α2-noradrenergic agonist, inhibited with a specific α2 antagonist and is abolished when G protein-coupled inwardly-rectifying potassium (GIRK) channels are blocked. Moreover, NE reduces the effective electrical coupling between GoCs through a persistent sodium current (INaP)-dependent mechanism. Our results suggest that NE controls the gain of the GoC inhibitory circuit by modulating membrane conductances that act to reduce membrane excitability and decrease electrical coupling. These mechanisms appear configured to reduce the level of GoC inhibition onto GCs during active behavioural states.

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Amines, Astrocytes, and Arousal

Cited by 31 publications

References 27 publications

Noradrenergic Transmission at Alpha1-Adrenergic Receptors in the Ventral Periaqueductal Gray Modulates Arousal

Noradrenergic Transmission at Alpha1-Adrenergic Receptors in the Ventral Periaqueductal Gray Modulates Arousal

α1b-Adrenergic Receptor Localization and Relationship to the D1-Dopamine Receptor in the Rat Nucleus Accumbens

Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer

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