Descoberto um 'controlador' de circuito cerebral: acaso, necessidade, design não inteligente ou design inteligente?

quarta-feira, dezembro 30, 2009

Scientists Discover a Controller of Brain Circuitry

ScienceDaily (Dec. 30, 2009) — By combining a research technique that dates back 136 years with modern molecular genetics, a Johns Hopkins neuroscientist has been able to see how a mammal's brain shrewdly revisits and reuses the same molecular cues to control the complex design of its circuits.


A pyramidal neuron in the mouse cerebral cortex is labeled using the Golgi technique. (Credit: Image by Tracy Tran, David Ginty and Alex Kolodkin of Johns Hopkins Medicine)

Details of the observation in lab mice, published Dec. 24 in Nature, reveal that semaphorin, a protein found in the developing nervous system that guides filament-like processes, called axons, from nerve cells to their appropriate targets during embryonic life, apparently assumes an entirely different role later on, once axons reach their targets. In postnatal development and adulthood, semaphorins appear to be regulating the creation of synapses -- those connections that chemically link nerve cells.

"With this discovery we're able to understand how semaphorins regulate the number of synapses and their distribution in the part of the brain involved in conscious thought," says David Ginty, Ph.D., a professor in the neuroscience department at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. "It's a major step forward, we believe, in our understanding of the assembly of neural circuits that underlie behavior."

Because the brain's activity is determined by how and where these connections form, Ginty says that semaphorin's newly defined role could have an impact on how scientists think about the early origins of autism, schizophrenia, epilepsy and other neurological disorders.

The discovery came as a surprise finding in studies by the Johns Hopkins team to figure out how nerve cells develop axons, which project information from the cells, as well as dendrites, which essentially bring information in. Because earlier work from the Johns Hopkins labs of Ginty and Alex Kolodkin, Ph.D., showed that semaphorins affect axon trajectory and growth, they suspected that perhaps these guidance molecules might have some involvement with dendrites.

Kolodkin, a professor in the neuroscience department at Johns Hopkins and a Howard Hughes Medical Institute investigator, discovered and cloned the first semaphorin gene in the grasshopper when he was a postdoctoral fellow. Over the past 15 years, numerous animal models, including strains of genetically engineered mice, have been created to study this family of molecules.
...

Read more here/Leia mais aqui.

+++++

Journal Reference:

Nature 462, 1065-1069 (24 December 2009) | doi:10.1038/nature08628; Received 3 September 2009; Accepted 30 October 2009; Published online 13 December 2009

Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS

Tracy S. Tran1,2, Maria E. Rubio3, Roger L. Clem1,2, Dontais Johnson1,2, Lauren Case4, Marc Tessier-Lavigne4,5, Richard L. Huganir1,2, David D. Ginty1,2 & Alex L. Kolodkin1,2

1. Solomon H. Snyder Department of Neuroscience,

2. Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

3. Departments of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA

4. Graduate Program in Neurosciences, Stanford University, Stanford, California 94305, USA

5. Division of Research, Genentech, South San Francisco, California 94080, USA

Correspondence to: David D. Ginty1,2Alex L. Kolodkin1,2 Correspondence and requests for materials should be addressed to D.D.G. (Email: dginty@jhmi.edu) and A.L.K. (Email: kolodkin@jhmi.edu).

Top of page

Abstract

The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines1, and spine morphology and distribution are critical for synaptic transmission2, 3, 4, 5, 6, synaptic integration and plasticity7. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn-2-/- brain slices cortical layer V and DG GCs exhibit increased mEPSC (miniature excitatory postsynaptic current) frequency. In contrast, a distinct Sema3A–Npn-1/PlexA4 signalling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn-2 to apical dendrites and of Npn-1 (also known as Nrp1) to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signalling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signalling events orchestrate CNS connectivity through the differential control of spine morphogenesis, synapse formation, and the elaboration of dendritic morphology.

+++++

Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao site CAPES/Periódicos podem ler gratuitamente este artigo da Nature e de mais 15 mil publicações científicas.