Ultrastructure and the chemical nature of the tripartite synapse
To know how the brain works we have to consider a whole anatomical and molecular networks between and among its major constituents (neurons and glial cells). The nervous information can be transmitted thanks to the release of neurotransmitters that activate the corresponding receptors located at the appropriate synapse. Thus, to understand the function of the brain and how it is regulated we need to elucidate if and how receptors are localized specifically in a cell. The mechanisms involved in the appropriate transport (targeting) of proteins in neurons are multiple, complex and are so far unclear. Less is known about receptor targeting in glial cells. Dr. Rubio’s laboratory is interested in analyzing these processes to understand the biology of neuron-glia interaction during normal and abnormal brain function.
The laboratory has the long-term-goal to investigate changes in receptor expression in response to experience. Because it is known that the composition of postsynaptic receptors affects the electrophysiological properties of neurons, it becomes important to analyze the changes in expression patterns when a particular source of activation is missing or somehow affected. In this context, we study the effects of an 8th nerve lesion and attenuation of sound on neurons of the cochlear nucleus complex. This is relevant for basic neuroscience, but this area of interest could have a strong clinical implication. Any information that might lead to new strategies of hearing loss treatment or the development of novel drugs would be valuable.
Trainees in Dr. Rubio’s laboratory have the opportunity to learn how to combine modern neuro-anatomical techniques coupled with immunocytochemistry at the light and electron microscopy levels. Immunocytochemistry, especially when combined with electron microscopic techniques, is a powerful technique that allows a detailed view and analysis of the expression and subcellular localization of receptors in the brain. Additionally, they will have the opportunity to explore new procedures to combine morphology with molecular, pharmacological and electrophysiological assays.
Tran, T.S., Rubio, M.E., Clem, R., Johnson, D., Case, L., Tessier-Lavigne, M., Huganir, R.L., Ginty, D.D. and Kolodkin, A.L. Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS Nature 2009, accepted.
Whiting, B., Moiseff, A. and Rubio, M.E. Cochlear nucleus neurons redistribute synaptic AMPA and glycine receptors in response to monaural conductive hearing loss. Neuroscience, 2009.
Gomez-Nieto, R. and Rubio, M.E. A bushy cell network in the rat ventral cochlear nucleus. J Comp Neurol 516: 241-263, 2009.
Rubio, M.E., Gudsnuk, K.A., Smith, Y. and Ryugo, D.K. Revealing the molecular layer of the primate dorsal cochlear nucleus. Neuroscience 154: 99-113, 2008.
Douyard, J., Shen, L., Huganir, R.L. and Rubio, M.E. Differential neuronal and glial expression of GluR1 AMPA receptor subunit, and the scaffolding proteins SAP97 and 4.1N during rat cerebellar development. J Comp Neurol 502: 141-156, 2007.