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[P2.24]: Aberrant striatal activity in mice with a mutation implicated in a developmental speech and language disorder
Author(s) -
French C.A.,
Jin X.,
Campbell T.G.,
Gerfen E.,
Groszer M.,
Fisher S.E.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.154
Subject(s) - human genetics , psychology , neuroscience , genetics , biology , gene
Transgenic mice expressing eGFP under population specific promoters are widely used in neuroscience research to identify specific subsets of neurons in situ. In addition, eGFP and destabilized derivatives have been developed as sensors of neuronal activity in vivo. Mice expressing eGFP from the Nr4a1 promoter have high expression within the basal ganglia, particularly within the striatal patch (striosome) compartment and striatal-like regions of the extended amygdala (BNST, striatal fundus, central nucleus and intercalated cells). Grossly, eGFP expression is the inverse of the matrix marker calbindin 28K and overlaps with mu-opioid receptor immunoreactivity and calretinin immunoreactivity in the medial and ventral striatum. Nr4a1-driven eGFP expression is similar to D1, but not D2, driven eGFP expression in striatal afferent structures. Striosomal localization is robust developmentally where Nr4a1-eGFP expression overlaps with D1, TrkB, TH and phospho-ERK, but not phospho-CREB, immunoreactivity in large islands. This pattern was similar to the pattern observed in the developing D1-eGFP mouse striatum. In order to examine the role of receptor stimulation in Nr4a1 promoter driven eGFP expression, primary cultures of medium spiny neurons prepared from neonatal mice and treated with BDNF, forskolin, or GPCR agonists for 24 h and eGFP was measured spectrofluorometrically in lysates. Agents that positively regulated eGFP expression included forskolin, BDNF and D1 agonists; carbachol produced a variable increase. The D2 and CB1 agonists modestly reduced eGFP levels. In addition, mice administered methylphenidate had higher eGFP levels in the dorsolateral striatal matrix 12 h after injection and a right-shifted intensity histogram indicative of increased striosomal expression. The Nr4a1-GFP mouse strain will be useful for examining developmental and activity-dependent changes in D1, cAMP and BDNF regulated direct pathway neurons but establishes a potential confound when using eGFP-expressing mouse strains in pharmacological and behavioral assays likely to result in changes in gene expression.