From Brownian motion to virtual biopsy: a historical perspective from 40 years of diffusion MRI.

Diffusion MRI was introduced in 1985, showing how the diffusive motion of molecules, especially water, could be spatially encoded with MRI to produce images revealing the underlying structure of biologic tissues at a microscopic scale. Diffusion is one of several Intravoxel Incoherent Motions (IVIM) accessible to MRI together with blood microcirculation. Diffusion imaging first revolutionized the management of acute cerebral ischemia by allowing diagnosis at an acute stage when therapies can still work, saving the outcomes of many patients.

From Black Holes Entropy to Consciousness: The Dimensions of the Brain Connectome.

It has been shown that the theory of relativity can be applied physically to the functioning brain, so that the brain connectome should be considered as a four-dimensional spacetime entity curved by brain activity, just as gravity curves the four-dimensional spacetime of the physical world. Following the most recent developments in modern theoretical physics (black hole entropy, holographic principle, AdS/CFT duality), we conjecture that consciousness can naturally emerge from this four-dimensional brain connectome when a fifth dimension is considered, in the same way that gravity emerges from a 'flat' four-dimensional quantum world, without gravitation, present at the boundaries of a five-dimensional spacetime. This vision makes it possible to envisage quantitative signatures of consciousness based on the entropy of the connectome and the curvature of spacetime estimated from data obtained by fMRI in the resting state (nodal activity and functional connectivity) and constrained by the anatomical connectivity derived from diffusion tensor imaging.

Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information.

Information-theoretic approach to detect directional information flow in EEG signals induced by TMS.

Effective connectivity analysis has been widely applied to noninvasive recordings such as functional magnetic resonance imaging and electroencephalograms (EEGs). Previous studies have aimed to extract the causal relations between brain regions, but the validity of the derived connectivity has not yet been fully determined. This is because it is generally difficult to identify causality in the usual experimental framework based on observations alone.

Overexpression of neuronal K-Cl co-transporter enhances dendritic spine plasticity and motor learning.

The neuronal K-Cl cotransporter KCC2 maintains a low intracellular Cl concentration and facilitates hyperpolarizing GABA receptor responses. KCC2 also plays a separate role in stabilizing and enhancing dendritic spines in the developing nervous system. Using a conditional transgenic mouse strategy, we examined whether overexpression of KCC2 enhances dendritic spines in the adult nervous system and characterized the effects on spine dynamics in the motor cortex in vivo during rotarod training.

Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms.

α2-Adrenoceptors are widely distributed throughout the central nervous system (CNS) and the systemic administration of α2-agonists such as dexmedetomidine produces clinically useful, centrally mediated sedation and analgesia; however, these same actions also limit the utility of these agents (ie, unwanted sedative actions). Despite a wealth of data on cellular and synaptic actions of α2-agonists in vitro, it is not known which neuronal circuits are modulated in vivo to produce the analgesic effect. To address this issue, we made in vivo recordings of membrane currents and synaptic activities in superficial spinal dorsal horn neurons and examined their responses to systemic dexmedetomidine.

Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 alpha and PKC.

The capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1), acts as a polymodal detector of pain-producing chemical and physical stimuli in sensory neurons. Hyperglycemia and hypoxia are two main phenomena in diabetes associated with several complications. Although many studies on streptozotocin-induced diabetic rats indicate that early diabetic neuropathy is associated with potentiation of TRPV1 activity in dorsal root ganglion neurons, its underlying mechanism and distinctive roles of hyperglycemia and hypoxia have not been completely clarified.

Excitation-contraction coupling in isolated locomotor muscle fibres from the pelagic tunicate Doliolum which lack both sarcoplasmic reticulum and transverse tubular system.

In the locomotor muscle of the pelagic tunicate Doliolum, both the sarcoplasmic reticulum (SR) and the transverse-tubular (T-tubular) system are absent. The mechanism of excitation-contraction (E-C) coupling was studied in single muscle fibres enzymatically dissociated from Doliolum denticulatum. Whole cell voltage clamp experiments demonstrated an inward ionic current associated with membrane depolarisation.

Systematic analysis of N-linked sugar chains from whole tissue employing partial automation.

A partially automated technique for the isolation and characterization of N-linked sugar chains from glycoproteins of crude tissue samples is established. The N-linked sugar chains from the acetone-extracted tissues are made free by a process of hydrazinolysis and subsequently N-acetylated by GlycoPrep 1000 (Oxford Glycosystems). These free sugar chains are further converted to pyridylamino derivatives by GlycoTag (Takara).