The Subfornical Organ: An Integrative Site for Reproductive, Cardiovascular, and Metabolic Control
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In order to maintain homeostasis, the central nervous system (CNS) must monitor and integrate signaling molecules such as peptides and hormones that convey information regarding reproductive, metabolic, and cardiovascular status (to name a few) of the organism. Many of these signals are located in circulation and are incapable of crossing the blood brain barrier (BBB), the protective structure surrounding the CNS. Circumventricular organs (CVOs) are specialized structures that lack a BBB and therefore provide a route through which these peripheral signals may access the CNS. This study focuses on the subfornical organ (SFO), a forebrain sensory CVO, and its ability to respond to three different signals, prolactin (PRL), alpha-melanocyte stimulating hormone (α-MSH) and brain derived neurotrophic factor (BDNF), which are involved in the regulation of reproductive, metabolic, and cardiovascular status, respectively. Using whole-cell and perforated patch-clamp recordings, all three peptides were found to influence the excitability of dissociated SFO neurons. Of the 9 neurons that responded to 1 µM PRL, 55% depolarized (mean: 13.6 ± 5.0 mV, n=5) and 45% hyperpolarized (mean:-8.4 ± 2.1 mV, n=4). Similar to this, 10 of the neurons perfused with 250 nM α-MSH responded by either depolarizing (50%, mean: 14.9 ± 5.6 mV, n=5) or hyperpolarizing (50%, mean: -11.0 ± 0.7 mV, n=5). Both response types were also observed in response to 1 nM BDNF as 69% of the 16 responders depolarized (mean: 15.4 ± 2.4 mV, n=11) and 31% hyperpolarized (mean: -12.1 ± 2.0 mV, n=5). A non-selective cation channel potentially mediates the depolarizing response of all three peptides, as suggested by comparing extrapolated reversal potentials for each (PRL: -61.7 mV, α-MSH –55.4 mV, BDNF: -53.3 mV). Additionally, some SFO neurons (12%) were capable of responding to both BDNF and α-MSH. This study is the first to demonstrate electrophysiological consequences of PRL, α-MSH, and BDNF on the excitability of SFO neurons, effects which provide a point at which these peptides could potentially access the CNS from the circulation. Given its numerous efferent projections to autonomic control centers of the CNS involved in reproductive, metabolic, and cardiovascular function, our data suggest the SFO is an important site of integration and information relay for these peptides.