Role of TRH/UCN3 neurons of the perifornical area/bed nucleus of stria terminalis region in the regulation of the anorexigenic POMC neurons of the arcuate nucleus in male mice and rats
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Two anorexigenic peptides, thyrotropin-releasing hormone (TRH) and urocortin 3 (UCN3), are co-expressed in a continuous neuronal group that extends from the perifornical area to the bed nucleus of stria terminalis, raising the possibility that this cell group may be involved in the regulation of energy homeostasis. In this study, therefore, we tested the hypothesis that the TRH/UCN3 neurons regulate food intake by influencing feeding-related neuropeptide Y (NPY) and/or proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC). Triple-labeled immunofluorescent preparations demonstrated that only very few NPY neurons (4.3 ± 1.3%) were contacted by double-labeled TRH/UCN3 axons in the ARC. In contrast, more than half of the POMC neurons (52.4 ± 8.5%) were contacted by double-labeled axons. Immuno-electron microscopy demonstrated that the UCN3 axons established asymmetric synapses with POMC neurons, indicating the excitatory nature of these synaptic specializations. Patch clamp electrophysiology revealed that TRH and UCN3 have antagonistic effects on the POMC neurons. While UCN3 depolarizes and increases the firing rate of POMC neurons, TRH prevents these effects of UCN3. These data demonstrate that TRH/UCN3 neurons in the perifornical/BNST region establish abundant synaptic associations with the POMC neurons in the ARC and suggest a potentially important role for these neurons in the regulation of food intake through an antagonistic interaction between TRH and UCN3 on the electrophysiological properties of POMC neurons.
KeywordsThyrotropin-releasing hormone Urocortin 3 Proopiomelanocortin Arcuate nucleus Perifornical region Bed nucleus of stria terminalis Antagonist effect
This work was supported by Grants from the Hungarian Science Foundation (OTKA K109710) and the Hungarian National Brain Research Program (KTIA_13_NAP_A_I/3).
ZP performed the electrophysiological experiments. EF were involved in the immunofluorescent studies, performed the immunostaining in mice, did the electron microscopy and were involved in the generation of the two novel antibodies. KN performed the first immunofluorescent studies and performed the quantitative analyses under the supervision of TF. AK were involved in the immunofluorescent studies. OS and AH were involved in the generation of the two novel antibodies. RML: data interpretation, manuscript preparation; CF: Experimental design, data acquisition, drafting, revising and interpretation of the work, takes primary responsibility.
Compliance with ethical standards
Conflict of interest
The authors have nothing to disclose.
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