Courtney L. Enix

Tulane University

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Pei‐San Tsai

University of Colorado Boulder

Andrea Zsombok

Tulane University

Imran J. Anwar

Duke Medical Center

Andrei V. Derbenev

Tulane University

Leah R. Brooks

Mallinckrodt (United States)

Christopher A. Lowry

University of Colorado Boulder

Kavon Rezai‐Zadeh

Pennington Biomedical Research Center

Heike Münzberg

Pennington Biomedical Research Center

Heide L. Pals

University of Colorado Boulder

Jinno A. Magno

University of Colorado Boulder

Cooperative Institutions

Tulane University

University of Colorado Boulder

Louisiana State University Health Sciences Center New Orleans

Pennington Biomedical Research Center

Louisiana State University

Toxicologie, Pharmacologie et Signalisation Cellulaire

Centre des Sciences du Goût et de l'Alimentation

Centre National de la Recherche Scientifique

Université de Bourgogne

Institut National de la Recherche Agronomique

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Fibroblast Growth Factor 8 Deficiency Compromises the Functional Response of the Serotonergic System to Stress

PLoS ONE (2014)

Leah R. Brooks Heide L. Pals Courtney L. Enix Rachel A. Woolaver Evan D. Paul

Functionally heterogeneous populations of serotonergic neurons, located within the dorsal raphe nucleus (DR), play a role in stress-related behaviors and neuropsychiatric illnesses such as anxiety and depression. Abnormal development of these neurons may permanently alter their structure and connections, making the organism more susceptible to anxiety-related disorders. A factor that critically regulates the development of serotonergic neurons is fibroblast growth factor 8 (Fgf8). In this study, we used acute restraint stress followed by behavioral testing to examine whether Fgf8 signaling during development is important for establishing functional stress- and anxiety-related DR neurocircuits in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8 were exposed to acute restraint stress and then tested for anxiety-like behavior on the elevated plus-maze. Further, we measured c-Fos immunostaining as a marker of serotonergic neuronal activation and tissue 5-hydroxyindoleacetic acid concentrations as a marker of serotonin functional output. Results showed that Fgf8 hypomorphs exhibited 1) an exaggerated response of DR anxiety-promoting circuits and 2) a blunted response of a DR panic-inhibiting circuit to stress, effects that together were associated with increased baseline anxiety-like behavior. Overall, our results provide a neural substrate upon which Fgf8 deficiency could affect stress response and support the hypothesis that developmental disruptions of serotonergic neurons affect their postnatal functional integrity.

Dorsal raphe nucleus

FGF8

Elevated plus maze

10.1371/journal.pone.0101420

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Interaction between TRPV1-expressing neurons in the hypothalamus

Journal of Neurophysiology (2018)

Adrien Molinas Lucie Desmoulins Brooke Victoria Hamling Sierra Morgan Butcher Imran J. Anwar

Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel expressed in the peripheral and central nervous systems. TRPV1-dependent mechanisms take part in a wide range of physiological and pathophysiological pathways including the regulation of homeostatic functions. TRPV1 expression in the hypothalamus has been described as well as evidence that TRPV1-dependent excitatory inputs to hypothalamic preautonomic neurons are diminished in diabetic conditions. Here we aimed to determine the functional expression of TRPV1 in two hypothalamic nuclei known to be involved in the central control of metabolism and to test the hypothesis that TRPV1-expressing neurons receive TRPV1-expressing inputs. A mouse model (TRPV1 Cre/tdTom ) was generated to identify TRPV1-expressing cells and determine the cellular properties of TRPV1-expressing neurons in adult mice. Our study demonstrated the functional expression of TRPV1 in the dorsomedial hypothalamic nucleus and paraventricular nucleus in adult mice. Our findings revealed that a subset of TRPV1 Cre/tdTom neurons receive TRPV1-expressing excitatory inputs, indicating direct interaction between TRPV1-expressing neurons. In addition, astrocytes likely play a role in the modulation of TRPV1-expressing neurons. In summary, this study identified specific hypothalamic regions where TRPV1 is expressed and functional in adult mice and the existence of direct connections between TRPV1 Cre/tdTom neurons. NEW & NOTEWORTHY Transient receptor potential vanilloid type 1 (TRPV1) is expressed in the hypothalamus, and TRPV1-dependent regulation of preautonomic neurons is decreased in hyperglycemic conditions. Our study demonstrated functional expression of TRPV1 in two hypothalamic nuclei involved in the control of energy homeostasis. Our results also revealed that a subset of TRPV1-expressing neurons receive TRPV1-expressing excitatory inputs. These findings suggest direct interaction between TRPV1-expressing neurons.

Energy homeostasis

Homeostasis

10.1152/jn.00004.2018

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Regulation of leptin receptor-expressing neurons in the brainstem by TRPV1

Physiological Reports (2014)

Andrea Zsombok Yanyan Jiang Hong Gao Imran J. Anwar Kavon Rezai‐Zadeh

The central nervous system plays a critical role in the regulation of feeding behavior and whole-body metabolism via controlling the autonomic output to the visceral organs. Activity of the parasympathetic neurons in the dorsal motor nucleus of the vagus (DMV) determines the vagal tone and thereby modulates the function of the subdiaphragmatic organs. Leptin is highly involved in the regulation of food intake and alters neuronal excitability of brainstem neurons. Transient receptor potential vanilloid type 1 (TRPV1) has also been shown to increase neurotransmission in the brainstem and we tested the hypothesis that TRPV1 regulates presynaptic neurotransmitter release to leptin receptor-expressing (LepRbEGFP) DMV neurons. Whole-cell patch-clamp recordings were performed to determine the effect of TRPV1 activation on excitatory and inhibitory postsynaptic currents (EPSC, IPSC) of LepRbEGFP neurons in the DMV. Capsaicin, a TRPV1 agonist increased the frequency of miniature EPSCs in 50% of LepRbEGFP neurons without altering the frequency of miniature IPSCs in the DMV. Stomach-projecting LepRbEGFP neurons were identified in the DMV using the transsynaptic retrograde viral tracer PRV-614. Activation of TRPV1 increased the frequency of mEPSC in ~50% of stomach-related LepRbEGFP DMV neurons. These data demonstrate that TRPV1 increases excitatory neurotransmission to a subpopulation of LepRbEGFP DMV neurons via presynaptic mechanisms and suggest a potential interaction between TRPV1 and leptin signaling in the DMV.

Dorsal motor nucleus

Premovement neuronal activity

10.14814/phy2.12160

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Citations (14)

Fibroblast growth factor deficiencies impact anxiety-like behavior and the serotonergic system

Behavioural Brain Research (2014)

Leah R. Brooks Courtney L. Enix Samuel C. Rich Jinno A. Magno Christopher A. Lowry

Dorsal raphe nucleus

FGF8

TPH2

10.1016/j.bbr.2014.01.053

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Citations (14)