LAUSR

The adipocyte-derived hormone leptin acts at leptin receptor (LepR)-expressing neurons in the brain to regulate metabolic and cardiovascular functions. LepR neurons in the dorsomedial hypothalamus (DMH) are required for leptin-induced feeding suppression, regulate brown adipose tissue thermogenesis and locomotor activity. We have previously identified these neurons as necessary for the hypertensive effects of hyperleptinemia in obesity. These neurons are heterogenous, with LepRs differentially co-expressed with metabolism-regulating peptides and receptors including, glucagon-like peptide 1 (GLP-1), agouti-related peptide (AgRP) and proopiomelanocortin (POMC). Variations in LepR neuron gene expression profiles may indicate differences in leptin responsiveness, function specificity and electrophysiological characteristics. Work presented here used in vitro visualized whole-cell patch clamp electrophysiology to characterise the electrophysiological properties of leptin-excited, leptin-inhibited, and non-responsive LepR neurons in the DMH of transgenic LepR-YFP mice. Whole cell current clamp recordings were obtained from 34 DMH LepR neurons and of these, bath application of 100 nM leptin excited 38% (n=13). Of some leptin excited LepR neurons, the effect was indirect via elevated spontaneous excitatory postsynaptic potential (EPSP) frequency (n=2). Of other leptin excited LepR neurons, membrane depolarisation was direct via the activation of one or more non-selective cation conductances (n=11). In two cases, leptin-induced sub and suprathreshold 'pacemaker like' oscillations in membrane potential. Of leptin-excited neurons 23% (n=3) of neurons expressed transient outward rectification ( ITR), 54% (n=7) expressed low-threshold t-type calcium conductances ( IT), 8% expressed instantaneous or anomalous inward rectification ( IAN) (n=1) and 15% expressed hyperpolarization-activated non-selective cation conductances ( IH) (n=2). Bath application of 100 nM leptin inhibited 15% of LepR neurons tested (n=5). these inhibitory membrane effects were postsynaptic and via the activation of one or more potassium conductances. Of leptin inhibited neurons 60% expressed ITR, 60% (n=3) expressed IT, 40% (n=3) expressed IAN and 40% (n=2) expressed IH. In 47% of neurons tested, bath application of leptin did not have any clear inhibitory or excitatory membrane (n=16). Of these non-responsive neurons 50% (n=8) expressed ITR, 44% (n=7) expressed IT, 44% (n=7) expressed IAN and 25% (n=4) expressed IH. Work presented highlights the heterogeneity of DMH LepR neurons and further indicates the existence of function-specific subpopulations. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.