Synapses of the mammalian CNS are highly specialized cellular junctions designed for rapid and regulated signaling between nerve cells and their targets. Abnormal synaptogenesis and synaptic reorganization in the developing CNS has been strongly correlated with developmental disorders such as fragile X, epilepsy, schizophrenia and mental retardation. Our ability to understand how different genetic and environmental insults cause cognitive dysfunction and mental retardation requires a better understanding of the cellular mechanisms that lead to the proper assembly and function of CNS synapses. This requires a molecular description of the constituents of synaptic junctions and the mechanisms used by neurons to correctly sort traffic and localized each component. Our studies of CNS synapses have led to the identification and characterization of numerous synaptic junctional proteins. One of the most recently identified, Bassoon, is a novel component of the presynaptic cytoskeletal matrix assembled at the active zone. Based on its structure on its structure and distribution, we hypothesize that it is involved in the assembly and function of CNS synapses. With regard to mental retardation and cognitive dysfunction, our analysis of the Bassoon gene and its transcripts have revealed the presence of a CAG expansion similar to these found Huntingtin, Ataxins and the Fragile X mental retardation Moreover, Basson expression is selectively enhance in a neurodegenerative disorder, multiple system atrophy. To gain insights into the role played by Bassoon in the presynaptic cytoskeletal matrix, we proposed to examine the mechanisms directing that transport and assembly of Bassoon at CNS synapses In addition we propose to assess the function of Bassoon in presynaptic nerve terminals by analyzing loss of function mutations in the mouse Bassoon gene Bsn on the structure, assembly, and function of CNS synapses in the developing mouse brain.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD038760-02
Application #
6491081
Study Section
Pediatrics Subcommittee (CHHD)
Project Start
2001-06-01
Project End
2002-05-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
$142,702
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Leuner, Kristina; Li, Wei; Amaral, Michelle D et al. (2013) Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels. Hippocampus 23:40-52
Speed, Haley E; Dobrunz, Lynn E (2008) Developmental decrease in short-term facilitation at Schaffer collateral synapses in hippocampus is mGluR1 sensitive. J Neurophysiol 99:799-813
Torres-Reveron, Juan; Friedlander, Michael J (2007) Properties of persistent postnatal cortical subplate neurons. J Neurosci 27:9962-74
Garner, Craig C; Waites, Clarissa L; Ziv, Noam E (2006) Synapse development: still looking for the forest, still lost in the trees. Cell Tissue Res 326:249-62
Pozzo-Miller, Lucas (2006) BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons. Brain Res 1104:45-54
Regalado, Maria Paz; Terry-Lorenzo, Ryan T; Waites, Clarissa L et al. (2006) Transsynaptic signaling by postsynaptic synapse-associated protein 97. J Neurosci 26:2343-57
Tyler, William J; Zhang, Xiao-lei; Hartman, Kenichi et al. (2006) BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses. J Physiol 574:787-803
Sun, Hua Yu; Dobrunz, Lynn E (2006) Presynaptic kainate receptor activation is a novel mechanism for target cell-specific short-term facilitation at Schaffer collateral synapses. J Neurosci 26:10796-807
Alonso, Mariana; Medina, Jorge H; Pozzo-Miller, Lucas (2004) ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. Learn Mem 11:172-8
Sontheimer, Harald (2004) Ion channels and amino acid transporters support the growth and invasion of primary brain tumors. Mol Neurobiol 29:61-71

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