A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Spelling dyslexia:a defict of the visual word form

A patient with spelling dyslexia read both words and text accurately but slowly and laboriously letter by letter. Her performance on a test of lexical decision was slow. She had great difficulty in detecting a 'rogue' letter attached to the beginning or end of a word--for example, ksong--or in parsing two unspaced words, such as applepeach. By contrast she was immune to the effects of interpolating extraneous coloured letters in a word, a manipulation that affects normal readers. Therefore it is argued that this patient had damage to an early stage in the reading process, to the visual word form itself

Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice

We developed a mouse model for central post-stroke pain (CPSP), a centrally-originated neuropathic pain (NeuP). In this mode, mice were first injected with Rose Bengal, followed by photo-irradiation of left middlecerebral artery (MCA) to generate thrombosis. Although the MCA thrombosis was soon dissolved, the reducedblood flow remained for more than 24 h due to subsequent occlusion of microvessels. This photochemicallyinduced thrombosis (PIT) model showed a hypersensitivity to the electrical stimulation of both sides of paw, butdid not show any abnormal pain in popular thermal or mechanical nociception tests. When tissue-type plas-minogen activator (tPA) was injected 6h after the PIT stress, tPA-dependent hypersensitivity to the electricalpaw stimulation and stable thermal and mechanical hyperalgesia on both sides for more than 17 or 18 days afterthe PIT treatment. These hyperalgesic effects were abolished in lysophosphatidic acid receptor 1 (LPA1)- andlysophosphatidic acid receptor 3 (LPA3)-deficient mice. When Ki-16425, an LPA1and LPA3antagonist wastreated twice daily for 6days consecutively, the thermal and mechanical hyperalgesia at day 17 and 18 weresignificantly reversed. The liquid chromatography?mass spectrometry (LC?MS/MS) analysis revealed that thereis a significant increase in several species of LPA molecules in somatosensory S-I and medial dorsal thalamus (MD), but not in striatum or ventroposterior thalamus. All these results suggest that LPA1and LPA3signalingplay key roles in the development and maintenance of CPSP

Investigating occipito-temporal contributions to reading with TMS.

The debate regarding the role of ventral occipito-temporal cortex (vOTC) in visual word recognition arises, in part, from difficulty delineating the functional contributions of vOTC as separate from other areas of the reading network. Here, we investigated the feasibility of using TMS to interfere with vOTC processing in order to explore its specific contributions to visual word recognition. Three visual lexical decision experiments were conducted using neuronavigated TMS. The first demonstrated that repetitive stimulation of vOTC successfully slowed word, but not nonword, responses. The second confirmed and extended these findings by demonstrating the effect was specific to vOTC and not present in the adjacent lateral occipital complex. The final experiment used paired-pulse TMS to investigate the time course of vOTC processing for words and revealed activation starting as early as 80-120 msec poststimulus onset-significantly earlier than that expected based on electrophysiological and magnetoencephalography studies. Taken together, these results clearly indicate that TMS can be successfully used to stimulate parts of vOTC previously believed to be inaccessible and provide a new tool for systematically investigating the information processing characteristics of vOTC. In addition, the findings provide strong evidence that lexical status and frequency significantly affect vOTC processing, findings difficult to reconcile with prelexical accounts of vOTC function.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe