21,519 research outputs found
Towards dynamical network biomarkers in neuromodulation of episodic migraine
Computational methods have complemented experimental and clinical
neursciences and led to improvements in our understanding of the nervous
systems in health and disease. In parallel, neuromodulation in form of electric
and magnetic stimulation is gaining increasing acceptance in chronic and
intractable diseases. In this paper, we firstly explore the relevant state of
the art in fusion of both developments towards translational computational
neuroscience. Then, we propose a strategy to employ the new theoretical concept
of dynamical network biomarkers (DNB) in episodic manifestations of chronic
disorders. In particular, as a first example, we introduce the use of
computational models in migraine and illustrate on the basis of this example
the potential of DNB as early-warning signals for neuromodulation in episodic
migraine.Comment: 13 pages, 5 figure
Optical excitation and detection of neuronal activity
Optogenetics has emerged as an exciting tool for manipulating neural
activity, which in turn, can modulate behavior in live organisms. However,
detecting the response to the optical stimulation requires electrophysiology
with physical contact or fluorescent imaging at target locations, which is
often limited by photobleaching and phototoxicity. In this paper, we show that
phase imaging can report the intracellular transport induced by optogenetic
stimulation. We developed a multimodal instrument that can both stimulate cells
with high spatial resolution and detect optical pathlength changes with
nanometer scale sensitivity. We found that optical pathlength fluctuations
following stimulation are consistent with active organelle transport.
Furthermore, the results indicate a broadening in the transport velocity
distribution, which is significantly higher in stimulated cells compared to
optogenetically inactive cells. It is likely that this label-free, contactless
measurement of optogenetic response will provide an enabling approach to
neuroscience.Comment: 20 pages, 5 figure
Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.
Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons
Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow
We review modeling of astrocyte ion dynamics with a specific focus on the
implications of so-called spatial potassium buffering, where excess potassium
in the extracellular space (ECS) is transported away to prevent pathological
neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for
modeling ion dynamics in astrocytes (and brain tissue in general) is outlined
and used to study such spatial buffering. We next describe how the ion dynamics
of astrocytes may regulate microscopic liquid flow by osmotic effects and how
such microscopic flow can be linked to whole-brain macroscopic flow. We thus
include the key elements in a putative multiscale theory with astrocytes
linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure
Neuronal Correlation Parameter in the Idea of Thermodynamic Entropy of an N-Body Gravitationally Bounded System
Understanding how the brain encodes information and performs computation requires statistical and functional analysis. Given the complexity of the human brain, simple methods that facilitate the interpretation of statistical correlations among different brain regions can be very useful. In this report we introduce a numerical correlation measure that may serve the interpretation of correlational neuronal data, and may assist in the evaluation of different brain states. The description of the dynamical brain system, through a global numerical measure may indicate the presence of an action principle which may facilitate a application of physics principles in the study of the human brain and cognition
Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling
We characterised the pathophysiology of seizure onset in terms of slow fluctuations in synaptic efficacy using EEG in patients with anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis. EEG recordings were obtained from two female patients with anti-NMDA-R encephalitis with recurrent partial seizures (ages 19 and 31). Focal electrographic seizure activity was localised using an empirical Bayes beamformer. The spectral density of reconstructed source activity was then characterised with dynamic causal modelling (DCM). Eight models were compared for each patient, to evaluate the relative contribution of changes in intrinsic (excitatory and inhibitory) connectivity and endogenous afferent input. Bayesian model comparison established a role for changes in both excitatory and inhibitory connectivity during seizure activity (in addition to changes in the exogenous input). Seizures in both patients were associated with a sequence of changes in inhibitory and excitatory connectivity; a transient increase in inhibitory connectivity followed by a transient increase in excitatory connectivity and a final peak of excitatory-inhibitory balance at seizure offset. These systematic fluctuations in excitatory and inhibitory gain may be characteristic of (anti NMDA-R encephalitis) seizures. We present these results as a case study and replication to motivate analyses of larger patient cohorts, to see whether our findings generalise and further characterise the mechanisms of seizure activity in anti-NMDA-R encephalitis
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