Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat

We recently found block of NO synthase in rat middle cerebral artery caused spasm, associated with depolarizing oscillations in membrane potential (Em) similar in form but faster in frequency (circa 1 Hz) to vasomotion. T-type voltage-gated Ca2+ channels contribute to cerebral myogenic tone and vasomotion, so we investigated the significance of T-type and other ion channels for membrane potential oscillations underlying arterial spasm. Smooth muscle cell membrane potential (Em) and tension were measured simultaneously in rat middle cerebral artery. NO synthase blockade caused temporally coupled depolarizing oscillations in cerebrovascular Em with associated vasoconstriction. Both events were accentuated by block of smooth muscle BKCa. Block of T-type channels or inhibition of Na+/K+-ATPase abolished the oscillations in Em and reduced vasoconstriction. Oscillations in Em were either attenuated or accentuated by reducing [Ca2+]o or block of KV, respectively. TRAM-34 attenuated oscillations in both Em and tone, apparently independent of effects against KCa3.1. Thus, rapid depolarizing oscillations in Em and tone observed after endothelial function has been disrupted reflect input from T-type calcium channels in addition to L-type channels, while other depolarizing currents appear to be unimportant. These data suggest that combined block of T and L-type channels may represent an effective approach to reverse cerebral vasospasm

Striatal hub of dynamic and stabilized prediction coding in forebrain networks for olfactory reinforcement learning

Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents

Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling

BACKGROUND AND PURPOSE: Controlling vascular tone involves K(+) efflux through endothelial cell small- and intermediate-conductance calcium-activated potassium channels (K(Ca)2.3 and K(Ca)3.1, respectively). We investigated the expression of these channels in astrocytes and the possibility that, by a similar mechanism, they might contribute to neurovascular coupling. EXPERIMENTAL APPROACH: Transgenic mice expressing enhanced green fluorescent protein (eGFP) in astrocytes were used to assess K(Ca)2.3 and K(Ca)3.1 expression by immunohistochemistry and RT-PCR. K(Ca) currents in eGFP-positive astrocytes were determined in situ using whole-cell patch clamp electrophysiology. The contribution of K(Ca)3.1 to neurovascular coupling was investigated in pharmacological experiments using electrical field stimulation (EFS) to evoke parenchymal arteriole dilatation in FVB/NJ mouse brain slices and whisker stimulation to evoke changes in cerebral blood flow in vivo, measured by laser Doppler flowmetry. KEY RESULTS: K(Ca)3.1 immunoreactivity was restricted to astrocyte processes and endfeet and RT-PCR confirmed astrocytic K(Ca)2.3 and K(Ca)3.1 mRNA expression. With 200 nM [Ca(2+)](i), the K(Ca)2.1-2.3/K(Ca)3.1 opener NS309 increased whole-cell currents. CyPPA, a K(Ca)2.2/K(Ca)2.3 opener, was without effect. With 1 µM [Ca(2+)](i), the K(Ca)3.1 inhibitor TRAM-34 reduced currents whereas apamin (K(Ca)2.1-2.3 blocker) had no effect. CyPPA also inhibited currents evoked by NS309 in HEK293 cells expressing K(Ca)3.1. EFS-evoked Fluo-4 fluorescence confirmed astrocyte endfoot recruitment into neurovascular coupling. TRAM-34 inhibited EFS-evoked arteriolar dilatation by 50% whereas charybdotoxin, a blocker of K(Ca)3.1 and the large-conductance K(Ca) channel, K(Ca)1.1, inhibited dilatation by 82%. TRAM-34 reduced the cortical hyperaemic response to whisker stimulation by 40%. CONCLUSION AND IMPLICATIONS: Astrocytes express functional K(Ca)3.1 channels, and these contribute to neurovascular coupling. LINKED ARTICLES: This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-

Astrocytes as brain interoceptors

Astrocytes form a vascular-neuronal interface and provide CNS neural networks with essential structural and metabolic support. They embrace all penetrating arterioles and capillaries, enwrap multiple neuronal somata, thousands of individual synapses, and upon activation release gliotransmitters (ATP, glutamate and D-serine) capable of modulating neuronal activity. The aim of this brief report is to review recent data implicating astrocytes in the brain mechanisms responsible for the detection of different sensory modalities and transmitting sensory information to the relevant neural networks controlling vital behaviours. The concept of astrocytes as brain interoceptors is strongly supported by our recent data obtained from studies of the central nervous mechanisms underlying the chemosensory control of breathing. At the level of the medulla oblongata, astrocytes indeed act as functional central respiratory chemoreceptors, sensing changes in the arterial blood and brain levels of /pH and then imparting these changes on the activity of the respiratory network to induce adaptive changes in lung ventilation.Astrocytes form a vascular-neuronal interface and provide CNS neural networks with essential structural and metabolic support. They embrace all penetrating arterioles and capillaries, enwrap multiple neuronal somata, thousands of individual synapses, and upon activation release gliotransmitters (ATP, glutamate and D-serine) capable of modulating neuronal activity. The aim of this brief report is to review recent data implicating astrocytes in the brain mechanisms responsible for the detection of different sensory modalities and transmitting sensory information to the relevant neural networks controlling vital behaviours. The concept of astrocytes as brain interoceptors is strongly supported by our recent data obtained from studies of the central nervous mechanisms underlying the chemosensory control of breathing. At the level of the medulla oblongata, astrocytes indeed act as functional central respiratory chemoreceptors, sensing changes in the arterial blood and brain levels of /pH and then imparting these changes on the activity of the respiratory network to induce adaptive changes in lung ventilation