ABSTRACT
As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.
Subject(s)
Magnetic Resonance Imaging/methods , Tauopathies/diagnosis , tau Proteins/metabolism , Alzheimer Disease/diagnosis , Animals , Biomarkers , Disease Models, Animal , Female , Mice , Mice, TransgenicABSTRACT
The generation of spikes by neurons is energetically a costly process and the evaluation of the metabolic energy required to maintain the signaling activity of neurons a challenge of practical interest. Neuron models are frequently used to represent the dynamics of real neurons but hardly ever to evaluate the electrochemical energy required to maintain that dynamics. This paper discusses the interpretation of a Hodgkin-Huxley circuit as an energy model for real biological neurons and uses it to evaluate the consumption of metabolic energy in the transmission of information between neurons coupled by electrical synapses, i.e., gap junctions. We show that for a single postsynaptic neuron maximum energy efficiency, measured in bits of mutual information per molecule of adenosine triphosphate (ATP) consumed, requires maximum energy consumption. For groups of parallel postsynaptic neurons we determine values of the synaptic conductance at which the energy efficiency of the transmission presents clear maxima at relatively very low values of metabolic energy consumption. Contrary to what could be expected, the best performance occurs at a low energy cost.
Subject(s)
Neurons/metabolism , Neurons/physiology , Action Potentials , Adenosine Triphosphate/chemistry , Animals , Axons , Biophysics/methods , Decapodiformes , Electrochemistry/methods , Gap Junctions , Hydrolysis , Ion Channels/chemistry , Membrane Potentials , Models, Neurological , Models, Statistical , Time FactorsABSTRACT
We have deduced an energy function for a Hindmarsh-Rose model neuron and we have used it to evaluate the energy consumption of the neuron during its signaling activity. We investigate the balance of energy in the synchronization of two bidirectional linearly coupled neurons at different values of the coupling strength. We show that when two neurons are coupled there is a specific cost associated to the cooperative behavior. We find that the energy consumption of the neurons is incoherent until very near the threshold of identical synchronization, which suggests that cooperative behaviors without complete synchrony could be energetically more advantageous than those with complete synchrony.
Subject(s)
Action Potentials/physiology , Biological Clocks/physiology , Energy Transfer/physiology , Models, Neurological , Nerve Net/physiology , Neurons/physiology , Synaptic Transmission/physiology , Animals , Computer Simulation , Humans , Membrane Potentials/physiologyABSTRACT
We argue that maintaining a synchronized regime between different chaotic systems requires a net flow of energy between the guided system and an external energy source. This energy flow can be spontaneously reduced if the systems are flexible enough as to structurally approach each other through an adequate adaptive change in their parameter values. We infer that this reduction of energy can play a role in the synchronization of bursting neurons and other natural oscillators.
Subject(s)
Biophysics/methods , Nonlinear Dynamics , Algorithms , Computer Simulation , Computers , Models, Statistical , Models, Theoretical , Monte Carlo Method , Software , Time FactorsABSTRACT
In this paper we present a method based on a generalized Hamiltonian formalism to associate to a chaotic system of known dynamics a function of the phase space variables with the characteristics of an energy. Using this formalism we have found energy functions for the Lorenz, Rössler, and Chua families of chaotic oscillators. We have theoretically analyzed the flow of energy in the process of synchronizing two chaotic systems via feedback coupling and used the previously found energy functions for computing the required energy to maintain a synchronized regime between systems of these families. We have calculated the flows of energy at different coupling strengths covering cases of both identical as well as nonidentical synchronization. The energy dissipated by the guided system seems to be sensitive to the transitions in the stability of its equilibrium points induced by the coupling.
ABSTRACT
A parameter-adaptive rule that globally synchronizes oscillatory Lorenz chaotic systems with initially different parameter values is reported. In principle, the adaptive rule requires access to the three state variables of the drive system but it has been readapted to work with the exclusive knowledge of only one variable, a potential message carrier. The rule is very robust and can be used to trace parameter modulation conveying hidden messages. The driven system is defined according to a drive-driven type of coupling that guarantees synchronization if parameters are identical. From any arbitrary initial state, the parameters of the driven system are dynamically adapted to reach convergence to the drive parameter values. At this point, synchronization mismatch or parameter tracing is used to unmask any potential hidden message.
