Impaired leptin responsiveness in the nucleus accumbens of leptin-overexpressing transgenic mice with dysregulated sucrose and lipid preference independent of obesity

The nucleus accumbens core (AcbC) is a striatal brain region essential for integrating motivated behavior and reward processing with premotor function. In humans and rodents, research has identified sex differences and sex steroid hormone sensitivity in AcbC-mediated behaviors, in disorders, and in rats in the electrophysiological properties of the AcbC output neuron type, the medium spiny neuron (MSN). It is unknown whether the sex differences detected in MSN electrophysiological properties extend to mice. Furthermore, MSNs come in distinct subtypes with subtle differences in electrophysiological properties, and it is unknown whether MSN subtype-specific electrophysiology varies by sex. To address these questions, we used male and female Drd1a-tdTomato line 6 bacterial artificial chromosome transgenic mice. We made acute brain slices of the AcbC, and performed whole cell patch-clamp recordings across MSN subtypes to comprehensively assess AcbC MSN subtype electrophysiological properties. We found that ( 1 mice MSNs did not exhibit the sex differences detected in rat MSNs, and 2) electrophysiological properties differed between MSN subtypes in both sexes, including rheobase, resting membrane potential, action potential properties, intrinsic excitability, input resistance in both the linear and rectified ranges, and miniature excitatory postsynaptic current properties. These findings significantly extend previous studies of MSN subtypes performed in males or animals of undetermined sex and indicate that the influence of sex upon AcbC MSN properties varies between rodent species. NEW & NOTEWORTHY This research provides the most comprehensive assessment of medium spiny neuron subtype electrophysiological properties to date in a critical brain region, the nucleus accumbens core. It additionally represents the first evaluation of whether mouse medium spiny neuron subtype electrophysiological properties differ by sex.

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Author response for "Estrogen receptor alpha, g‐protein coupled receptor 1, and aromatase: developmental, sex, and region‐specific differences across the rat caudate‐putamen, nucleus accumbens core and shell"

10.1002/cne.24978/v4/response1 ◽

2020 ◽

Author(s):

Amanda A. Krentzel ◽

Jaime A. Willett ◽

Ashlyn G. Johnson ◽

John Meitzen

Keyword(s):

Estrogen Receptor ◽

Nucleus Accumbens ◽

G Protein ◽

Estrogen Receptor Alpha ◽

Author Response ◽

G Protein Coupled Receptor ◽

Nucleus Accumbens Core ◽

Caudate Putamen ◽

Receptor Alpha ◽

G Protein Coupled

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Author response for "Estrogen receptor alpha, g‐protein coupled receptor 1, and aromatase: developmental, sex, and region‐specific differences across the rat caudate‐putamen, nucleus accumbens core and shell"

10.1002/cne.24978/v3/response1 ◽

2020 ◽

Author(s):

Amanda A. Krentzel ◽

Jaime A. Willett ◽

Ashlyn G. Johnson ◽

John Meitzen

Keyword(s):

Estrogen Receptor ◽

Nucleus Accumbens ◽

G Protein ◽

Estrogen Receptor Alpha ◽

Author Response ◽

G Protein Coupled Receptor ◽

Nucleus Accumbens Core ◽

Caudate Putamen ◽

Receptor Alpha ◽

G Protein Coupled

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Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162533 ◽

1996 ◽

Vol 54 ◽

pp. 14-15

Author(s):

C. G. Plopper ◽

C. Helton ◽

A. J. Weir ◽

J. A. Whitsett ◽

T. R. Korfhagen

Keyword(s):

Growth Factor ◽

Pulmonary Fibrosis ◽

Transgenic Mice ◽

Blood Vessels ◽

Lung Parenchyma ◽

Lung Maturation ◽

Alveolar Air ◽

Parenchymal Tissue ◽

Air Space ◽

Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

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