Abstract
Transgenic mice expressing eGFP under population specific promoters are widely used in neuroscience to identify specific subsets of neurons in situ and as sensors of neuronal activity in vivo. Mice expressing eGFP from a bacterial artificial chromosome under the Nr4a1 promoter have high expression within the basal ganglia, particularly within the striosome compartments and striatal-like regions of the extended amygdala (bed nucleus of the stria terminalis, striatal fundus, central amygdaloid nucleus and intercalated cells). Grossly, eGFP expression is inverse to the matrix marker calbindin 28K and overlaps with mu-opioid receptor immunoreactivity in the striatum. This pattern of expression is similar to Drd1, but not Drd2, dopamine receptor driven eGFP expression in structures targeted by medium spiny neuron afferents. Striosomal expression is strong developmentally where Nr4a1-eGFP expression overlaps with Drd1, TrkB, tyrosine hydroxylase and phospho-ERK, but not phospho-CREB, immunoreactivity in “dopamine islands”. Exposure of adolescent mice to methylphenidate resulted in an increase in eGFP in both compartments in the dorsolateral striatum but eGFP expression remained brighter in the striosomes. To address the role of activity in Nr4a1-eGFP expression, primary striatal cultures were prepared from neonatal mice and treated with forskolin, BDNF, SKF-83822 or high extracellular potassium and eGFP was measured fluorometrically in lysates. eGFP was induced in both neurons and contaminating glia in response to forskolin but SKF-83822, brain derived neurotrophic factor and depolarization increased eGFP in neuronal-like cells selectively. High levels of eGFP were primarily associated with Drd1+ neurons in vitro detected by immunofluorescence; however ∼15% of the brightly expressing cells contained punctate met-enkephalin immunoreactivity. The Nr4a1-GFP mouse strain will be a useful model for examining the connectivity, physiology, activity and development of the striosome system.
Highlights
Principle neurons in the telencephalon are organized into layers with distinct circuit and ensemble functions that can be surmised based on the location of the nuclei but the anatomical organization of the striatum has proven more challenging
Distribution of Nr4a1-eGFP in the Mature Basal Ganglia Nr4a1 promoter driven eGFP expression was observed in distinct cell populations throughout the brain and periphery
S1 and S2). eGFP levels were high in the mature striatum but the pattern was distinct from both Drd1-eGFP and Drd2-eGFP expression (Fig. 1)
Summary
Principle neurons in the telencephalon are organized into layers with distinct circuit and ensemble functions that can be surmised based on the location of the nuclei but the anatomical organization of the striatum has proven more challenging. This is because the striatum does not possess the readily identified laminar organization of most telencephalic structures and because the majority of striatal neurons are of one class, the GABAergic Medium Spiny Neuron (MSN) [1]. The striatum is grossly divided into Dorsolateral (DLS), Dorsomedial (DMS) and ventral/Nucleus Accumbens (NAc). Regions can readily be identified for gross analysis but there is yet another layer of afferent-efferent and neurochemical heterogeneity within the striatum, the striosome-matrix organization
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