Nicotinic alpha4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits

ANA PAULA GARCÍA; TEEMU AITTA-AHO; LAURA SCHAAF; NICHOLAS HEELE; LENA HEUSCHMID; YUNJING BAI; FRANCISCO J BARRANTES; JOHN APERGIS-SCHOUTE

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015

1932-6203

Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite andhave been shown to do so by influencing neural activity in the hypothalamus. To shed lighton the hypothalamic circuits governing acetylcholine?s (ACh) regulation of appetite thisstudy investigated the influence of hypothalamic nAChRs expressing the α4 subunit. Wefound that antagonizing the alpha4beta2 nAChR locally in the lateral hypothalamus with di-hydro beta-erythroidine (DHbetaE), an alpha4 nAChR antagonist with moderate affinity, caused an increasein food intake following free access to food after a 12 hour fast, compared to saline-infusedanimals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, andtyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamusexpressed the nAChR alpha4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively)whereas melanin concentrating hormone (MCH) neurons did not, suggesting thatDHbetaE-mediated increases in food intake may be due to a direct activation of specific hypothalamiccircuits. Systemic DHbetaE (2 mg/kg) administration similarly increased food intakefollowing a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neuronsshowed elevated activity compared to control animals and MCH neuronal activity was overalllower as measured by expression of the immediate early gene marker for neuronal activitycFos. However, oxytocin neurons in the paraventricular hypothalamus and THcontainingneurons in the A13 and A12 did not show differential activity patterns. Theseresults indicate that various neurochemically distinct hypothalamic populations are underthe influence of alpha4beta2 nAChRs and that cholinergic inputs to the lateral hypothalamus canaffect satiety signals through activation of local alpha4beta2 nAChR-mediated transmission.