Trends in Neurosciences
OpinionDoes glutamate image your thoughts?
Section snippets
Energetic cost of glutamate transmission
The majority of neuronal information is conveyed via the rapid, excitatory glutamate-mediated system: 80–90% of cortical synapses are glutamergic [7]. Therefore, an important energy load is created by the operation of glutamatergic synapses. Moreover, a growing body of experimental data indicates that the activity of these synapses is tightly regulated by dynamic interactions between astrocytes and neurons (Fig. 2). The different steps in glutamate-mediated transmission include action
What triggers the increase in glucose uptake during activation?
Although the studies already mentioned demonstrate a quantitative relationship between cortical energy expenditure and glutamate-mediated neurotransmission, they do not relate glucose consumption to specific processes directly. In other words, we do not know which signaling pathway enables tight adjustment of glucose use (as seen by FDG-PET) to meet the increasing needs of the glutamatergic synapses. In addition to the possible dynamic regulation of glucose entry into neurons via the neuronal
What triggers the increase in blood flow during activation?
Despite a century of research, it is still unclear how the vascular supply of glucose and oxygen adapts to the changing needs of neurons (for a comprehensive review, see Ref. [25]). Roy and Sherrington's ‘in series’ hypothesis suggested that increased neuronal activity leads to the accumulation of vasoactive catabolites, such as H+, K+ and adenosine, which decrease vascular resistance and thus increase blood flow until normal conditions are re-established [26]. However, this hypothesis could
A role for astrocytes in neurovascular coupling?
It has recently emerged that cell types other than neurons might also be involved in glutamate-induced functional hyperemia. Indeed, the notion that astrocytes are active components of glutamate-mediated transmission has received strong experimental support over the last three years [45]. In addition to the fact that these glial cells are strategically positioned close to the vasculature, they can sense glutamate through functional NMDA [46] and non-NMDA [47] receptors, and can respond to
Concluding remarks
Although data do not provide yet definitive answers, they do suggest that glutamate could coordinate both the vascular and the metabolic responses to neuronal activity that underlie functional imaging signal changes. These effects of glutamate could involve its receptor-mediated action on neurons and/or astrocytes (metabolic and vascular responses), and its transport within the astrocyte (metabolic responses). These data support the notion that functional imaging signals are closely linked to
Acknowledgements
The research of G.B. was supported by the CNRS and the Human Frontier Science Program Organization (RG118/1998-B). The research of N.S. was supported by the National Institute of Health, USA (DK-27121) and the Medical Research Council, UK. L.P. received financial support from the Human Frontier Science Program Organization (RG118/1998-B) and from Swiss Fonds National de la Recherche Scientifique (56930.99). We thank D. Slosman, Hopitaux Universitaires de Genève, Geneva, Switzerland, for the
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2016, Journal of Affective DisordersCitation Excerpt :The coordination of glutamatergic neurons is believed to have a direct impact on BOLD signal contrast, since up to 85% of the brain energy is used to support glutamatergic signaling (Hu et al.,2013). Glu could coordinate both the vascular and metabolic responses to neuronal activity underlying functional imaging signal changes (Bonvento et al., 2002; Duncan et al., 2011). In the mPFC, the concentration of Glu predicted the degree of functional connectivity between mPFC and various subcortical regions (Duncan et al., 2013).