Like any technology, μMRI and μPET have appropriate and inappropriate uses. Dr. Russell Jacobs will discuss why one might bother with either. Then, he will present a range of applications: how 3D atlas of mouse and quail can be created from high resolution MR images; delve into how lesions and brain structure changes in mouse models of multiple sclerosis are amenable to study with MRI; and describe how statistical parametric mapping (SPM) of multiple MRI brain scans of monoamine transporter KO mouse models provide information about neuronal circuitry alterations. Monitoring changes in tumor physiology is an important aspect of both clinical and pre-clinical imaging - ADC and cell tracking work will be discussed. Recording of μPET and μMR images simultaneously is a recent development with a host of uses and abuses - Dr. Jacobs will present on work in mouse models of atherosclerosis and oncology that require the sensitivity of μPET and resolution with anatomical context of μMRI.

There is a great need today for tools that can search personal genome sequences for damaged genes and disease-causing variants. In response, the Yandell Lab has developed VAAST, the Variant Annotation, Analysis and Search Tool. VAAST is a new kind of tool: a probabilistic disease-gene finder. VAAST substantially improves upon existing approaches in terms of statistical power, flexibility and scope of use. VAAST can identify rare-disease causing loci with perfect accuracy in situations where existing methodologies often fail: using single trios of family members, and in small cohorts (n=3) where no two individuals share the same deleterious variants. VAAST can also identify genes involved in common, complex diseases using many fewer cases than traditional GWAS analyses. VAAST thus enables even modestly funded investigators to carry out effective hunts for rase and common disease genes.

Dr. Juo will describe genes and mechanisms that regular glutamate receptor trafficking and abundance at synapses in C. elegans. In particular, he will address how ubiquitin and the deubiquitinating enzyme USP-46 protect glutamate receptors from degradation in the lysosome.

Serial two-photon (STP) tomography, an automated method, achieves high-throughput fluorescence imaging of whole rodent size organs by integrating two-photon microsopy and tissue sectioning. In particular, STP tomography can generate high-resolution datasets of mouse brains that are free of distortions and can be readily warped in three dimensions onto standard brain atlases. This method opens the door to routine systematic studies of neuroanatomy in mouse models of human brain disorders.

Genetic studies of Alzheimer's disease reveal that over 20 genes cause or contribute to risk for developing the disease. Similar studies of frontotemporal dementia and motor neuron disease also have successfully identified genes that contribute to neurodegeneration. These groups of disorders are all characterized, but the accumulation of misfolded proteins suggests there may be a common underlying mechanism.

Tryptophan is the precursor for both the serotonin and kynurenine pathways, both of which play important roles in prenatal and postnatal development. The role of these pathways in autism spectrum disorders and in tuberous sclerosis complex, a genetic disorder with a high prevalence of epilepsy and autism, will be discussed.

Tryptophan is the precursor for both the serotonin and kynurenine pathways, both of which play important roles in prenatal and postnatal development. The role of these pathways in autism spectrum disorders and in tuberous sclerosis complex, a genetic disorder with a high prevalence of epilepsy and autism, will be discussed.

Mitochondria are dynamic organelles that fuse, divide, and move. Human genetic studies indicate that these processes are important for normal functioning of tissues, particularly neurons. Mutations in Mfn2 cause peripheral neuropathy (Charcot-Marie-Tooth 2A), and mutations in OPA1 cause eye disease (dominant optic atrophy). Mouse knockout studies focused on the mitofusins Mfn1 and Mfn2 have shown that mitochondrial fusion is important for organellar function. I will discuss mouse studies that reveal the physiological functions of mitochondrial dynamics. In addition, I will discuss how new mouse models can be combined with imaging approaches to understand the role of mitochondrial dynamics in neurodegeneration.

Spatiotemporal regulation of actin network assembly-disassembly cycles coordinated with myosin II contractility is fundamental to all forms of directed cell motility and the related process of axon or neurite growth. In this seminar I will compare and contrast how the treadmilling actin filament arrays resulting from the above processes behave in two different contexts: 1) substrate dependent neurite outgrowth and 2) outgrowth triggered by a soluble chemotropic factor. How traction and protrusive forces that drive neurite growth will be considered for each growth regime. If I have time I will present some new results re the role of the Arp2/3 actin nucleation complex in regulation growth cone structure and function.

Genomewide datasets are useful for studying biological diversity within a tumor sample collection. This is evidenced by numerous reports in the past decade for the discovery of cancer subtypes using gene expression data. Today, the same tumor samples are often analyzed simultaneously for genomic, epigenomic, transcriptomic, and other –omics profiles. How to combine these data in cancer classification remains a difficult task.

In my group we have wrestled with issues such as data integration, within-tumor heterogeneity, inference of component cell types, validation, and clinical relevance. I will share some of the lessons learned from analyzing the glioblastoma datasets from The Cancer Genome Atlas Project. Our efforts uncovered pitfalls in some commonly adopted strategies, and led to new insights into glioblastoma evolution and subtype diversity.

A major challenge in mental health research is to understand how genes and experiences affect the functional architectures and developmental trajectories of brain circuits underlying cognitive functions. Research in Dr. Wang’s laboratory focuses on developing in vivo approaches that integrate a variety of molecular genetic, multi-photon imaging, optical stimulation, and electrophysiology techniques to reveal experience-dependent regulation of cortical circuits and dissect underlying mechanisms. Recent progress in visual cortical circuits and prefrontal cortical circuits will be discussed, as well as the implications of these studies for designing therapeutic strategies to enhance healthy brain functioning.

LPA (lysophosphatidic acid) is a membrane-derived bioactive lipid present throughout the body including brain and blood. Over the last 15 years, mechanisms underlying LPA’s extracellular signaling activities have been clarified through the identification of cognate G protein-coupled receptors that have revealed a rich biology with therapeutic potential. This lecture will cover some of the history and background of LPA signaling, with a focus on its effects in the prenatal cerebral cortex and in developmental brain disorders such as a most common neurological disorder of newborns and children, congenital hydrocephalus. Alterations in LPA signaling may possibly explain known disease risk factors of hemorrhage and hypoxia for hydrocephalus, along with other developmentally arising neuropsychiatric conditions.

In the course of generating intracellular compartments membranes must undergo shaping consisting of two consecutive geometrical transformations: generation of curvature and remodeling of curvature by fission. We ask whether a single protein can drive the whole process of membrane shaping or whether the two transformations require different proteins. The two major mechanisms of membrane curvature generation by proteins are: membrane scaffolding by protein domains with an intrinsic curvature and insertion of hydrophobic protein regions into the membrane matrix. Here we use elastic models of lipid bilayers and protein scaffolds to demonstrate that the hydrophobic insertion mechanism can drive membrane fission in addition to membrane bending. We analyze quantitatively the conditions of membrane fission by this mechanism and demonstrate their biological feasibility taking the epsin ENTH domain and the N-BAR domains of endophilin and amphiphysin as paradigm proteins. We predict that epsin will be more liable to promote membrane fission and we also predict a difference in the abilities of endophilin and amphiphysin to induce membrane fission. We propose that the suggested mechanism may underlie membrane remodeling by numerous proteins known to have a potential to bend membranes by the hydrophobic insertion mechanism.

The presentation will first provide a review of how multisensory function shapes normal behavior and perception, as well as a brief overview of its neural underpinnings. This will be followed by a review of current work characterizing the development of multisensory neural systems, as well as the plasticity inherent in these systems. Finally, recent evidence will be highlighted suggesting dysfunction in multisensory integration in developmental disabilities such as autism.

Michael Stryker is the William Francis Ganong Professor in the Department of Physiology at the University of California, San Francisco, where he has been a faculty member since his appointment as Assistant Professor in 1978, serving as Department Chair from 1994-2005. He earned his B.A. in Philosophy and Mathematics from the University of Michigan, Ann Arbor and his Ph.D. from the Massachusetts Institute of Technology. From 1976-1978 he was Research Fellow in Neurobiology at Harvard Medical School, where he worked with Nobel Laureates Torsten Wiesel and David Hubel.

Stryker has received several honors and awards for his research, including election to membership in the National Academy of Sciences and the American Academy of Arts and Sciences and appointment as the Galileo Galilei Professor of Science at Scuola Normale Superiore in Pisa, Italy (1993). Other honors include the W. Alden Spencer Award from Columbia University and selection as a Fellow of the American Association for the Advancement of Science.

His scientific work concerns the mechanisms of development, activity-dependent plasticity and recovery of function in the central nervous system, focusing particularly on the mammalian visual cortex and superior colliculus. He and his students have also developed technology to carry out novel experiments.

The neurovascular unit (NVU) comprises vascular cells (endothelium, pericytes, and vascular smooth muscle cells (VSMCs)), glial cells (astrocytes, microglia and oliogodendroglia) and neurons. Recent evidence suggests that microvascular dysfunction, neurovascular disintegration and defective blood-brain barrier (BBB) function may contribute to the development of Alzheimer’s disease (AD). The processes involved in BBB breakdown at the molecular and cellular levels and the consequences of BBB breakdown/dysfunction, hypoperfusion and hypoxia for neuronal function, including evidence suggesting that vascular defects precede neuronal dysfunction will be discussed. Disrupted cell-to-cell signaling within the NVU will be reviewed such as (i) platelet-derived growth factor receptor β deficiency causing pericytes degeneration which results in BBB breakdown and hypoperfusion preceding neurodegenerative changes; (ii) regulation of the key neurovascular functions in the adult and aging brain by apolipoprotein E (apoE) genotype including evidence that astrocyte-secreted apoE4 (APOE-e4 is the major genetic risk factor for AD) activates a proinflammatory cyclophilin A-NF-kB-matrix-metalloproteinase-9 pathway in cerebral pericytes causing BBB breakdown and microvascular reductions prior to neuronal dysfunction; and (iii) alterations in the expression of the vascular-specific genes discovered through genome-wide transcriptional profiling of brain endothelium (i.e, MEOX2) and VSMCs (i.e., MYOCARDIN) in AD causing aberrant angiogenic responses, vascular regression, blood flow reductions and faulty amyloid-b clearance. Novel therapeutic opportunities relating to these neurovascular deficits will be discussed.

In this seminar I will discuss the influence of light on our biological clock, sleep and mood. I
will concentrate on the atypical ganglion cell photoreceptors in the mammalian retina, known
as melanopsin expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). I will then present the contribution of the classical photoreceptors rods and cones to the above mentioned functions and provide recent data on the retinal circuits that signal the light information to the brain.