Featured Research

Targeting Seizure-Induced Neurogenesis in a Clinically-Relevant Time Period Leads to Transient but not Persistent Seizure Reduction

Parul Varma, Rebecca Brulet, Ling Zhang, and Jenny Hsieh

Removing new neurons born after a brain injury reduces seizures in mice, an approach that could potentially help prevent post-injury epilepsy. New neurons generated following a brain injury often do not develop normally. Left untreated, these cells may contribute to the development of epilepsy.

Jenny Hsieh and colleagues at the University of Texas at San Antonio continually removed new neurons that formed during the 8 weeks following a seizure in mice. Hsieh’s team monitored seizure activity in the mice and observed that the treated mice experienced a 65 percent reduction in seizures compared to the untreated mice. This effect required more than four weeks of continuous treatment.

Although these findings support a role for newborn neurons in epilepsy development, they also suggest additional factors are involved. Further research may bring us closer to complete prevention of injury-induced epilepsy.

Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain

Joseph R. Winer, Bryce A. Mander, Randolph F. Helfrich, Anne Maass, Theresa M. Harrison, Suzanne L. Baker, Robert T. Knight, William J. Jagust, and Matthew P. Walker

Several studies have linked sleep disruption to the progression of Alzheimer’s disease (AD). Tau and β-amyloid (Aβ), the primary pathological features of AD, are associated with both objective and subjective changes in sleep. However it remains unknown whether late life tau and Aβ burden are associated with distinct impairments in sleep physiology or changes in sleep across the lifespan. Using polysomnography, retrospective questionnaires, and tau- and Aβ-specific positron emission tomography, the present study reveals human sleep signatures which dissociably predict levels of brain tau and Aβ in older adults. These results suggest that a night of polysomnography may aid in evaluating tau and Aβ burden, and that treating sleep deficiencies within decade-specific time windows may serve in delaying AD progression.

N-Cadherin Orchestrates Self-Organization of Neurons Within a Columnar Unit in the Drosophila Medulla

Olena Trush, Chuyan Liu, Xujun Han, Yasuhiro Nakai, Rie Takayama, Hideki Murakawa, Jose A. Carrillo, Hiroki Takechi, Satoko Hakeda-Suzuki, Takashi Suzuki, and Makoto Sato

The columnar structure is a basic unit of the brain, but its developmental mechanism remains unknown. The medulla, the largest ganglion of the fly visual center, provides a unique opportunity to reveal the mechanisms of three-dimensional organization of the columns. We reveal that column formation is initiated by three core neurons that establish distinct concentric domains within a column. We demonstrate the in vivo evidence of N-cadherin-dependent differential adhesion among the core columnar neurons within a column along a two-dimensional layer in the larval medulla. The two-dimensional larval columns evolve to form three distinct layers in the pupal medulla. We propose the presence of mutual interactions among the three layers during formation of the three-dimensional structures of the medulla columns.

Perceptual Function and Category-Selective Neural Organization in Children with Resections of Visual Cortex

Tina T. Liu, Erez Freud, Christina Patterson, and Marlene Behrmann

One approach to reduce seizure activity in patients with pharmaco-resistant epilepsy involves the resection of the epileptogenic focus. The impact of these resections on the perceptual behaviors and organization of visual cortex remain largely unexplored. Here, we characterized the visuoperceptual and neural profiles of ventral visual cortex in a relatively large sample of post-resection pediatric patients. Two major findings emerged. First, most patients exhibited preserved visuoperceptual performance across a wide-range of visual behaviors. Second, normal topography, magnitude, and representational structure of category-selective organization was uncovered in the spared hemisphere. These comprehensive imaging and behavioral investigations uncovered novel evidence concerning the neural representations and visual functions in children who have undergone cortical resection, and have implications for cortical plasticity more generally.

A Neuroanatomical Substrate Linking Perceptual Stability to Cognitive Rigidity in Autism

Takamitsu Watanabe, Rebecca P. Lawson, Ylva S.E. Walldén, and Geraint Rees

Behavioural studies show perceptual over-stability in autism spectrum disorder (ASD). However, neural mechanisms by which such sensory symptoms can coexist and often correlate with seemingly separate core symptoms remain unknown. Here, we have identified such a key neuroanatomical substrate. We have revealed that over-stable sensory perception of individuals with autism is linked with their cognitive rigidity, a part of core restricted, repetitive behaviours symptoms, and such a behavioural link is underpinned by a smaller grey matter volume in the posterior superior parietal lobule in autism. These findings uncover a key neuroanatomical mediator of autistic perceptual and cognitive inflexibility and would ignite future studies on how the core symptoms of autism interact with its unique sensory perception.

Metformin Promotes Anxiolytic and Antidepressant-like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

J. Zemdegs, H. Martin, H. Pintana, S. Bullich, S. Manta, M.A. Marqués, C. Moro, S. Layé, F. Ducrocq, N. Chattipakorn, S.C. Chattipakorn, C. Rampon, L. Pénicaud, X. Fioramonti, and B.P. Guiard

Insulin resistance in humans is associated with increased risk of anxio-depressive disorders. Such relationship has been also found in rodents fed a High Fat Diet (HFD). To determine whether insulin-sensitizing strategies induce anxiolytic- and/or antidepressant-like activities and to investigate the underlying mechanisms, we tested the effects of metformin, an oral antidiabetic drug, in mice fed a HFD. Metformin reduced levels of circulating branched-chain amino acids which regulate tryptophan uptake within the brain. Moreover, metformin increased hippocampal serotonergic neurotransmission while promoting anxiolytic- and antidepressant-like effects. Moreover, a diet poor in these amino acids produced similar beneficial behavioral property. Collectively, these results suggest that metformin could be used as add-on therapy to conventional antidepressant for the comorbidity between metabolic and mental disorders.