235 research outputs found
Global and regional brain metabolic scaling and its functional consequences
Background: Information processing in the brain requires large amounts of
metabolic energy, the spatial distribution of which is highly heterogeneous
reflecting complex activity patterns in the mammalian brain.
Results: Here, it is found based on empirical data that, despite this
heterogeneity, the volume-specific cerebral glucose metabolic rate of many
different brain structures scales with brain volume with almost the same
exponent around -0.15. The exception is white matter, the metabolism of which
seems to scale with a standard specific exponent -1/4. The scaling exponents
for the total oxygen and glucose consumptions in the brain in relation to its
volume are identical and equal to , which is significantly larger
than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on
body mass.
Conclusions: These findings show explicitly that in mammals (i)
volume-specific scaling exponents of the cerebral energy expenditure in
different brain parts are approximately constant (except brain stem
structures), and (ii) the total cerebral metabolic exponent against brain
volume is greater than the much-cited Kleiber's 3/4 exponent. The
neurophysiological factors that might account for the regional uniformity of
the exponents and for the excessive scaling of the total brain metabolism are
discussed, along with the relationship between brain metabolic scaling and
computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen
Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution
It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution
Advances in MRI-Based Detection of Cerebrovascular Changes after Experimental Traumatic Brain Injury
Traumatic brain injury is a heterogeneous and multifaceted neurological disorder that involves diverse pathophysiological pathways and mechanisms. Thorough characterization and monitoring of the brain’s status after neurotrauma is therefore highly complicated. Magnetic resonance imaging (MRI) provides a versatile tool for in vivo spatiotemporal assessment of various aspects of central nervous system injury, such as edema formation, perfusion disturbances and structural tissue damage. Moreover, recent advances in MRI methods that make use of contrast agents have opened up additional opportunities for measurement of events at the level of the cerebrovasculature, such as blood–brain barrier permeability, leukocyte infiltration, cell adhesion molecule upregulation and vascular remodeling. It is becoming increasingly clear that these cerebrovascular alterations play a significant role in the progression of post-traumatic brain injury as well as in the process of post-traumatic brain repair. Application of advanced multiparametric MRI strategies in experimental, preclinical studies may significantly aid in the elucidation of pathomechanisms, monitoring of treatment effects, and identification of predictive markers after traumatic brain injury
Physical and Functional Interaction of NCX1 and EAAC1 Transporters Leading to Glutamate-Enhanced ATP Production in Brain Mitochondria
Glutamate is emerging as a major factor stimulating energy production in CNS. Brain mitochondria can utilize this neurotransmitter as respiratory substrate and specific transporters are required to mediate the glutamate entry into the mitochondrial matrix. Glutamate transporters of the Excitatory Amino Acid Transporters (EAATs) family have been previously well characterized on the cell surface of neuronal and glial cells, representing the primary players for glutamate uptake in mammalian brain. Here, by using western blot, confocal microscopy and immunoelectron microscopy, we report for the first time that the Excitatory Amino Acid Carrier 1 (EAAC1), an EAATs member, is expressed in neuronal and glial mitochondria where it participates in glutamate-stimulated ATP production, evaluated by a luciferase-luciferin system. Mitochondrial metabolic response is counteracted when different EAATs pharmacological blockers or selective EAAC1 antisense oligonucleotides were used. Since EAATs are Na+-dependent proteins, this raised the possibility that other transporters regulating ion gradients across mitochondrial membrane were required for glutamate response. We describe colocalization, mutual activity dependency, physical interaction between EAAC1 and the sodium/calcium exchanger 1 (NCX1) both in neuronal and glial mitochondria, and that NCX1 is an essential modulator of this glutamate transporter. Only NCX1 activity is crucial for such glutamate-stimulated ATP synthesis, as demonstrated by pharmacological blockade and selective knock-down with antisense oligonucleotides. The EAAC1/NCX1-dependent mitochondrial response to glutamate may be a general and alternative mechanism whereby this neurotransmitter sustains ATP production, since we have documented such metabolic response also in mitochondria isolated from heart. The data reported here disclose a new physiological role for mitochondrial NCX1 as the key player in glutamate-induced energy production
Frontal GABA Levels Change during Working Memory
Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing
Neuron-glial Interactions
Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Junior Leader Fellowship Program by “la Caixa” Banking Foundation (LCF/BQ/LI18/11630006
Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression
Role of the lesion scar in the response to damage and repair of the central nervous system
Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation
Neuron-Glial Interactions
Although lagging behind classical computational neuroscience, theoretical and
computational approaches are beginning to emerge to characterize different
aspects of neuron-glial interactions. This chapter aims to provide essential
knowledge on neuron-glial interactions in the mammalian brain, leveraging on
computational studies that focus on structure (anatomy) and function
(physiology) of such interactions in the healthy brain. Although our
understanding of the need of neuron-glial interactions in the brain is still at
its infancy, being mostly based on predictions that await for experimental
validation, simple general modeling arguments borrowed from control theory are
introduced to support the importance of including such interactions in
traditional neuron-based modeling paradigms.Comment: 43 pages, 2 figures, 1 table. Accepted for publication in the
"Encyclopedia of Computational Neuroscience," D. Jaeger and R. Jung eds.,
Springer-Verlag New York, 2020 (2nd edition
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