One of the most fascinating questions facing neuroscience is how the nervous system learns. Recent studies indicate that this process involves changes in neuronal morphology and synaptic efficacy. In addition, defects in these processes underlie mental retardation and other neuropsychiatric diseases. Accordingly, we are studying neuronal signaling pathways that mediate these forms of "plasticity".

Current projects include studies of:

1)Tech: This protein is a member of the RhoGEF family which plays a key role in regulating the actin cytoskeleton. We have found that Tech is selectively expressed in neurons of the cortex and hippocampus and that overexpression of an active form of Tech triggers retraction of dendrites. Accordingly, Tech may mediate dendritic re-modeling induced during learning. Current efforts are focusing on determing how Tech activity is regulated and its role in physiological forms of plasticity.

2) The Translin/Trax RNA binding complex- Translin and Trax are partner proteins that bind to RNA in vitro and have been implicated in suppressing RNA translation in peripheral cells. In recent studies, we have obtained evidence that this complex is located in neuronal dendrites. Accordingly, we are currently investigating the hypothesis that the Translin/Trax complex regulates local control of dendritic RNA translation in response to synaptic stimulation.

3) Narp: The Worley has demonstrated that Narp is an immediate early gene that is capable of clustering AMPA receptors. Since changes in AMPA receptor function have been linked to the long-term effects of drugs of abuse, we have examined whether Narp may mediate long-term aversive responses induced by opiate withdrawal. We have found that Narp is strongly induced in the amygdala, a structure that encodes aversive responses. Accordingly, current efforts are aimed at testing the hypothesis that Narp mediates long-term aversive responses induced by drug withdrawal that are thought to play a key role in sustaining drug abuse.

Publications:

Shiota J, Ishikawa M, Sakagami H, Tsuda M, Baraban JM, Tabuchi A. (2006) Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology. J. Neurochem. 98:1778-88.
PubMed Abstract

Blouin AM, Thannickal TC, Worley PF, Baraban JM, Reti IM, Siegel JM. (2005)Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy. Neurology. 2005 65(8):1189-92.
PubMed Abstract

Tabuchi A, Estevez M, Henderson JA, Marx R, Shiota J, Nakano H, Baraban JM. (2005) Nuclear translocation of the SRF co-activator MAL in cortical neurons: role of RhoA signalling. J Neurochem. 94:169-80.
PubMed Abstract

Marx R, Henderson J, Wang J, Baraban JM. 2005. Tech: a RhoA GEF selectively expressed in hippocampal and cortical neurons. J Neurochem. 92:850-8.
PubMed Abstract