The contribution of astrocytes to the regulation of cerebral blood flow

In order to maintain normal brain function, it is critical that cerebral blood flow (CBF) is matched to neuronal metabolic needs. Accordingly, blood flow is increased to areas where neurons are more active (a response termed functional hyperemia). The tight relationships between neuronal activation, glial cell activity, cerebral energy metabolism, and the cerebral vasculature, known as neurometabolic and neurovascular coupling, underpin functional MRI (fMRI) signals but are incompletely understood. As functional imaging techniques, particularly BOLD fMRI, become more widely used, their utility hinges on our ability to accurately and reliably interpret the findings. A growing body of data demonstrates that astrocytes can serve as a “bridge,” relaying information on the level of neural activity to blood vessels in order to coordinate oxygen and glucose delivery with the energy demands of the tissue. It is widely assumed that calcium-dependent release of vasoactive substances by astrocytes results in arteriole dilation and the increased blood flow which accompanies neuronal activity. However, the signaling molecules responsible for this communication between astrocytes and blood vessels are yet to be definitively confirmed. Indeed, there is controversy over whether activity-induced changes in astrocyte calcium are widespread and fast enough to elicit such functional hyperemia responses. In this review, I will summarize the evidence which has convincingly demonstrated that astrocytes are able to modify the diameter of cerebral arterioles. I will discuss the prevalence, presence, and timing of stimulus-induced astrocyte calcium transients and describe the evidence for and against the role of calcium-dependent formation and release of vasoactive substances by astrocytes. I will also review alternative mechanisms of astrocyte-evoked changes in arteriole diameter and consider the questions which remain to be answered in this exciting area of research

Contributions and complexities from the use of in-vivo animal models to improve understanding of human neuroimaging signals.

Many of the major advances in our understanding of how functional brain imaging signals relate to neuronal activity over the previous two decades have arisen from physiological research studies involving experimental animal models. This approach has been successful partly because it provides opportunities to measure both the hemodynamic changes that underpin many human functional brain imaging techniques and the neuronal activity about which we wish to make inferences. Although research into the coupling of neuronal and hemodynamic responses using animal models has provided a general validation of the correspondence of neuroimaging signals to specific types of neuronal activity, it is also highlighting the key complexities and uncertainties in estimating neural signals from hemodynamic markers. This review will detail how research in animal models is contributing to our rapidly evolving understanding of what human neuroimaging techniques tell us about neuronal activity. It will highlight emerging issues in the interpretation of neuroimaging data that arise from in-vivo research studies, for example spatial and temporal constraints to neuroimaging signal interpretation, or the effects of disease and modulatory neurotransmitters upon neurovascular coupling. We will also give critical consideration to the limitations and possible complexities of translating data acquired in the typical animals models used in this area to the arena of human fMRI. These include the commonplace use of anaesthesia in animal research studies and the fact that many neuropsychological questions that are being actively explored in humans have limited homologues within current animal models for neuroimaging research. Finally we will highlighting approaches, both in experimental animals models (e.g. imaging in conscious, behaving animals) and human studies (e.g. combined fMRI-EEG), that mitigate against these challenges

Couche limite et sillage d'un profil d'aile muni d'un volet battant

CNRS TD Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Context sensitivity of activity-dependent increases in cerebral blood flow

Functional neuroimaging in humans is used widely to study brain function in relation to human disease and cognition. The neural basis of neuroimaging signals is probably synaptic activity, but the effect of context, defined as the interaction between synaptic inhibition, excitation, and the electroresponsive properties of the targeted neurons, is not well understood. We examined here the effect of interaction of synaptic excitation and net inhibition on the relationship between electrical activity and vascular signals in the cerebellar cortex. We show that stimulation of the net inhibitory parallel fibers simultaneously with stimulation of the excitatory climbing fibers leads to a further rise in total local field potentials (LFP) and cerebral blood flow (CBF) amplitudes, not a decrease, as predicted from theoretical studies. However, the combined stimulation of the parallel and climbing fiber systems produced changes in CBF and LFP that were smaller than their algebraic sum evoked by separate stimulation of either system. This finding was independent of the starting condition, i.e., whether inhibition was superimposed on a state of excitation or vice versa. The attenuation of the increases in LFP and CBF amplitudes was similar, suggesting that synaptic activity and CBF were coupled under these conditions. The result might be explained by a relative neuronal refractoriness that relates to the intrinsic membrane properties of Purkinje cells, which determine the recovery time of these cells. Our work implies that neuronal and vascular signals are context-sensitive and that their amplitudes are modulated by the electroresponsive properties of the targeted neurons