Fasted/fed states regulate postsynaptic hub protein DYNLL2 and glutamatergic transmission in oxytocin neurons in the hypothalamic paraventricular nucleus.
The neurons in the hypothalamus regulate food intake and energy metabolism on reception of systemic energy states. Accumulating evidences have indicated that synaptic transmission on the hypothalamic neurons is modulated by the metabolic condition related to fasted/fed states, and that this modulation of synaptic plasticity plays a role in regulation of feeding. It has been shown that oxytocin (Oxt) neurons in the paraventricular nucleus (PVN) of the hypothalamus sense and integrate various peripheral and central signals and thereby induce satiety. However, whether metabolic conditions regulate the synaptic transmission on Oxt neurons in PVN remains unclear. The present study examined whether the fasted/fed states regulate synaptic transmission on Oxt neurons in PVN. The miniature excitatory postsynaptic currents (mEPSCs) onto Oxt neurons in PVN were increased under ad lib fed condition compared to 24h fasted condition. Furthermore, the NMDA receptor-mediated EPSC on Oxt neurons was increased under fed, compared to fasted, condition. In Oxt neurons, dynein light chain 2 (DYNLL2), a protein suggested to be implicated in the NMDA receptor trafficking to the postsynaptic site, was increased under fed, compared to fasted, condition. The present results suggest that feeding increases excitatory synaptic input on PVN Oxt neurons via mechanisms involving DYNLL2 upregulation and NMDA receptor-mediated synaptic reorganization.
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Shigetomo
S
Suyama
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Misato
M
Kodaira-Hirano
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Zesemdorj
Z
Otgon-Uul
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Yoichi
Y
Ueta
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Masanori
M
Nakata
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan; Division of Adaptation Development, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan. Electronic address: tyada@jichi.ac.jp.
Toshihiko
T
Yada
D000818:Animals; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D005215:Fasting; D008297:Male; D055369:Miniature Postsynaptic Potentials; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D010121:Oxytocin; D056445:Cytoplasmic Dyneins; C000613030:DYNLL2 protein, rat
DYNLL2; Fasting; Feeding; NMDA receptor; Oxytocin; Paraventricular nucleus; Proteomics; Slice patch clamp; Synaptic plasticity