Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells - PubMed (original) (raw)

Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells

Christa M Patterson et al. Brain Res. 2011.

Abstract

Leptin acts via the long form of the leptin receptor (LepRb) on specialized sets of neurons in the brain to modulate diverse functions in concert with energy stores. Previous studies have revealed the distribution of LepRb-expressing neurons in the brain but not the regions to which LepRb neurons project to mediate downstream leptin actions. We utilized LepRb-cre in combination with cre-inducible enhanced green fluorescent protein (EGFP) and farnesylated EGFP (EGFPf) mouse reporter strains to visualize LepRb neurons and their projections, respectively, throughout the brain. The areas containing LepRb soma and projections were relatively circumscribed, as many brain regions contained no detectable EGFP or EGFPf. The highest concentrations of LepRb neurons and LepRb projections were found in the hypothalamus, where the ventral premamillary (PMv), dorsomedial (DMH), and arcuate (ARC) nuclei contained the greatest number of cell bodies, in addition to substantial EGFPf-reactivity. Furthermore, both LepRb soma and projections were present in a few midbrain and brainstem nuclei. Several brain regions including the hypothalamic paraventricular nucleus (PVH), the anteroventral periventricular nucleus (AVPe), and the central nucleus of the amygdala (CeA) contained few LepRb neurons but substantial EGFPf, suggesting that these regions represent targets of LepRb neurons that lie elsewhere in the brain. In some nuclei that contained both soma and projections, the distribution of soma and projections differed, suggesting that these areas transmit leptin-encoded information in a neuroanatomically directional manner.

Copyright © 2011 Elsevier B.V. All rights reserved.

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Figures

Figure 1

Figure 1. LepRbEGFP and LepRbEGFPf reporter mice

a) Schematic diagram demonstrating cre-mediated EGFP and EGFPf expression in LepRb expressing cells of LepRbEGFP and LepRbEGFPf mice. In each line, cre-dependent excision of a transcription-blocking cassette induces the expression of EGFP or EGFPf in LepRb neurons of mice expressing cre recombinase from the LepRb-specific mRNA.

Figure 2

Figure 2. LepRbEGFP and LepRbEGFPf reporter mice reveal LepRb neurons and projections in the hypothalamus and surrounding regions

Representative fluorescent images (4x) of EGPF-IR of brain sections from LepRbEGFP (left panels) and LepRbEGFPf (right panels (′)) mice in the mid-hypothalamus (A, A′) at the level of the ARC and DMH and at the level of the PMv (B, B′). Higher magnification (10x) images of the indicated regions in A, A′ show the DMH (Aa, Aa′) and ARC (Ab, Ab′). Higher magnification (10X) images of the indicated regions in B, B′ show the PMv (Ba, Ba′). 3v, third-ventricle.

Figure 3

Figure 3. LepRbEGFP and LepRbEGFPf reporter mice reveal LepRb neurons and projections in the midbrain

Representative fluorescent images (4x) of EGPF-IR of brain sections from LepRbEGFP (first and third columns) and LepRbEGFPf (second and fourth columns (′)) mice in the midbrain (A, A′) at the level of the VTA and at the level of the DR (B, B′). Higher magnification (10x) images of the indicated regions in A, A′ show the LiR (Aa, Aa′), EW (Ab, Ab′), and VTA (Ac, Ac′). Higher magnification (10X) images of the indicated regions in B, B′ show the DR (Ba, Ba′) and PAG (Bb, Bb′). Aq, aqueduct.

Figure 4

Figure 4. LepRbEGFP and LepRbEGFPf reporter mice reveal LepRb neurons and projections in the hindbrain

Representative fluorescent images (4x) of EGPF-IR of brain sections from LepRbEGFP (left panels) and LepRbEGFPf (right panels (′)) mice in the hindbrain at the level of the LPBN (A, A′) and at the level of the AP and NTS (B, B′). Higher magnification (10x) images of the indicated regions in A, A′ show the LPBN (Aa, Aa′). Higher magnification (10X) images of the indicated regions in B, B′ show the NTS (Ba, Ba′). Aq, aqueduct.

Figure 5

Figure 5. LepRbEGFP and LepRbEGFPf reporter mice reveal anatomical regions innvervated by LepRb neurons and largely lacking LepRb soma

Representative fluorescent images (4x) of EGPF-IR of brain sections from LepRbEGFP (first and third columns) and LepRbEGFPf (second and fourth columns (′)) mice in the rostral hypothalamus at the level of the POA and NAc (A, A′), at the level of the PVH (B, B′) and the mid-hypothalamus/amygdala at the level of the CeA (C, C′). Higher magnification (10x) images of the indicated regions in A, A′ show the POA (Aa, Aa′), and NAc (at the border with the BNST) (Ab, Ab′). Higher magnification (10X) images of the indicated regions in B, B′ show the PVH (Ba, Ba′). Higher magnification (10X) images of the indicated regions in C, C′ show the CeA (Ca, Ca′). 3v, third ventricle; Ac, anterior commissure.

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