Glycemic State Regulates Brain Derived Neurotrophic Factor Responsiveness of Neurons in the Paraventrucular Nucleus

Abstract

Brain derived neurotrophic factor (BDNF) is a chemical messenger that has been implicated in the central control of food intake and regulation of the stress axis. Consistent with a role in feeding behavior, TrkB, the receptor through which BDNF exerts its effects, is expressed in the paraventricular nucleus (PVN). The PVN is a complex integrative autonomic centre with critical roles in the coordinated control of food intake. Recently, studies have shown that glucose‐sensing neurons in areas of the hypothalamus, including PVN, exhibit altered excitability in response to changes in extracellular glucose. Here, whole cell current‐clamp recordings were employed on rat PVN neurons in slice preparation to evaluate the ability of these cells to integrate multiple metabolically relevant signals. BDNF (2nM) was bath applied in both high (10mM) and low (0.2mM) extracellular glucose concentrations. BDNF applied to PVN neurons (N=48) in 10mM glucose elicited varying responses with 50% depolarizing (mean change in membrane potential ± standard error: 9.0 ± 1.2 mV), 23% hyperpolarizing (mean: ‐6.7 ± 1.4 mV), and 27% showing no response to BDNF treatment. However, BDNF's effects were profoundly altered in hypoglycemic conditions. BDNF application to PVN neurons in 0.2mM glucose (N=15) elicited primarily hyperpolarizing effects (73%, mean: ‐6.4 ± 0.9 mV) apart from one cell that depolarized (7%, mean: 4.8 mV). Our findings demonstrate the potential role of BDNF in feeding through its impact on the excitability of PVN neurons and how these responses are altered by glycemic state.