in-vivo-three-dimensional-two-photon-microscopy-to-study-conducted

In Vivo Three-Dimensional Two-Photon Microscopy to Study Conducted Vascular Responses by Local ATP Ejection Using a Glass Micro-Pipette

Maintenance of normal brain function requires a sufficient and efficient supply of oxygen and nutrition by a complex network of vessels. However, the ...

University of Copenhagen

One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar cortex is well suited for addressing this problem because synaptic input to and spiking of the principal cell, the Purkinje cell (PC), are spatially segregated. Also, PCs are pacemakers, able to generate spikes endogenously. We examined the contributions to cerebellar cortical oxygen consumption (CMRO2) of postsynaptic excitation and PC spiking during evoked and ongoing neuronal activity in the rat. By inhibiting excitatory synaptic input using ionotropic glutamate receptor blockers, we found that the increase in CMRO2 evoked by parallel fiber (PF) stimulation depended entirely on postsynaptic excitation. In contrast, PC spiking was largely responsible for the increase in CMRO2 when ongoing neuronal activity was increased by gamma-aminobutyric acid type A receptor blockade. In this case, CMRO2 increased equally during PC spiking with excitatory synaptic activity as during PC pacemaker spiking without excitatory synaptic input. Subsequent inhibition of action potential propagation and neurotransmission by blocking voltage-gated Na+-channels eliminated the increases in CMRO2 due to PF stimulation and increased PC spiking, but left a large fraction of CMRO2, i.e., basal CMRO2, intact. In conclusion, whereas basal CMRO2 in anesthetized animals did not seem to be related to neurosignaling, increases in CMRO2 could be induced by all aspects of neurosignaling. Our findings imply that CMRO2 responses cannot a priori be assigned to specific neuronal activities.

Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex.

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB hippocampus, but not in CSB cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

Delirium is common during sepsis, although under-recognized. We aimed to assess the value of continuous electroencephalography (cEEG) to aid in the diagnosis of delirium in septic patients.

Article	Year
Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex. Journal of neurophysiology\| PubMed ID: 19571198	2009
Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus. Neurobiology of aging\| PubMed ID: 29031832	2018
Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium. Neurocritical care\| PubMed ID: 30891696	2019

Kirsten J. Thomsen

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