GABA; LH; amygdala; glutamate; kisspeptin; Gonadotropin-Releasing Hormone; Luteinizing Hormone; gamma-Aminobutyric Acid; Arcuate Nucleus of Hypothalamus; Endocrinology, Diabetes and Metabolism; Endocrinology; Endocrine and Autonomic Systems; Cellular and Molecular Neuroscience
Abstract :
[en] Kisspeptin neurons in the arcuate nucleus of the hypothalamus generate gonadotrophin-releasing hormone (GnRH) pulses, and act as critical initiators of functional gonadotrophin secretion and reproductive competency. However, kisspeptin in other brain regions, most notably the posterodorsal subnucleus of the medial amygdala (MePD), plays a significant modulatory role over the hypothalamic kisspeptin population; our recent studies using optogenetics have shown that low-frequency light stimulation of MePD kisspeptin results in increased luteinsing hormone pulse frequency. Nonetheless, the neurochemical pathways that underpin this regulatory function remain unknown. To study this, we have utilised an optofluid technology, precisely combining optogenetic stimulation with intra-nuclear pharmacological receptor antagonism, to investigate the neurotransmission involved in this circuitry. We have shown experimentally and verified using a mathematical model that functional neurotransmission of both GABA and glutamate is a requirement for effective modulation of the GnRH pulse generator by amygdala kisspeptin neurons.
Lass, Geffen; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Li, Xiao Feng; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Voliotis, Margaritis ; Department of Mathematics and Living Systems Institute, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK
Wall, Ellen; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK ; Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
de Burgh, Ross A; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Ivanova, Deyana; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Mcintyre, Caitlin ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau ; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Lin, Xian-Hua; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Colledge, William H; Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
Lightman, Stafford L ; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, The Dorothy Hodgkin Building, University of Bristol, Bristol, UK
Tsaneva-Atanasova, Krasimira; Department of Mathematics and Living Systems Institute, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK
O'Byrne, Kevin T ; Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
Language :
English
Title :
GnRH pulse generator frequency is modulated by kisspeptin and GABA-glutamate interactions in the posterodorsal medial amygdala in female mice.
BBSRC - Biotechnology and Biological Sciences Research Council EPSRC - Engineering and Physical Sciences Research Council
Funding text :
We are extremely grateful for all the help and advice on optogenetics provided by Dr Matt Grubb, Centre for Developmental Neurobiology, Faculty of Life Sciences and Medicine, King's College London, UK. We also gratefully acknowledge the financial support from the MRC (MR/N022637/1) and BBSRC (BB/S000550/1). Tsaneva-Atanasova K gratefully acknowledges the financial support of the EPSRC via grant EP/T017856/1. Voliotis M and Tsaneva-Atanasova K gratefully acknowledge the financial support of the BBSRC via grants BB/S001255/1, BB/S019979/1 and BB/W005883/1. Lass G and Ivanova D are funded by MRC PhD studentships. Colledge WH acknowledges the support of the Ford Physiology Fund Endowment.We are extremely grateful for all the help and advice on optogenetics provided by Dr Matt Grubb, Centre for Developmental Neurobiology, Faculty of Life Sciences and Medicine, King's College London, UK. We also gratefully acknowledge the financial support from the MRC (MR/N022637/1) and BBSRC (BB/S000550/1). Tsaneva\u2010Atanasova K gratefully acknowledges the financial support of the EPSRC via grant EP/T017856/1. Voliotis M and Tsaneva\u2010Atanasova K gratefully acknowledge the financial support of the BBSRC via grants BB/S001255/1, BB/S019979/1 and BB/W005883/1. Lass G and Ivanova D are funded by MRC PhD studentships. Colledge WH acknowledges the support of the Ford Physiology Fund Endowment.
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