5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens

Abstract

Miller RL, Loewy AD. 5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens. Am J Physiol Regul Integr Comp Physiol 306: R663-R673, 2014. First published March 5, 2014 doi:10.1152/ajpregu.00563.2013 neurons of the area postrema (AP) represent one neuronal phenotype implicated in the regulation of salt appetite. Tryptophan hydroxylase (Tryp-OH, synthetic enzyme-producing 5-HT) immunoreactive neurons in the AP of rats become c-Fos-activated following conditions in which plasma sodium levels are elevated; these include intraperitoneal injections of hypertonic saline and sodium repletion. Non-Tryp-OH neurons also became c-Fos-activated. Sodium depletion, which induced an increase in plasma osmolality but caused no significant change in the plasma sodium concentration, had no effect on the c-Fos activity in the AP. Epithelial sodium channels are expressed in the Tryp-OH-immunoreactive AP neurons, possibly functioning in the detection of changes in plasma sodium levels. Since little is known about the neural circuitry of these neurons, we tested whether the AP contributes to a central pathway that innervates the reward center of the brain. Stereotaxic injections of pseudorabies virus were made in the nucleus accumbens (NAc), and after 4 days, this viral tracer produced retrograde transneuronal labeling in the Tryp-OH and non-Tryp-OH AP neurons. Both sets of neurons innervate the NAc via a multisynaptic pathway. Besides sensory information regarding plasma sodium levels, the AP¡NAc pathway may also transmit other types of chemosensory information, such as those related to metabolic functions, food intake, and immune system to the subcortical structures of the reward system. Because these subcortical regions ultimately project to the medial prefrontal cortex, different types of chemical signals from visceral systems may influence affective functions. area postrema; circumventricular organs; epithelial sodium channels; nucleus accumbens; ventral tegmental area THE AREA POSTREMA (AP) IS a sensory circumventricular organ (CVO) located in the dorsal midline of the medulla oblongata, which protrudes into the 4th ventricle. Its terminal arterial supply is made up of fenestrated capillaries with pores measuring ϳ60 -80 nm, which allow the passage of solutes and small peptides from the plasma into the AP, so the local neurons and glial cells are bathed in a similar chemical environment as the plasma. CVO neurons detect small changes in the plasma concentration of many of these chemicals and convert this information into neural activity that is sent via feed-forward excitatory pathways to homeostatic regulatory sites in the hypothalamus. For example, the forebrain CVO neurons, originating in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), project to the vasopressin and oxytocin neurons of the supraoptic and paraventricular hypothalamic nuclei and elicit the release of these hormones that...

Mapping brain Fos immunoreactivity in response to water deprivation and partial rehydration: Influence of sodium intake

“…For example, sodium-sensitive neurons are present in the NTS and AP [13,30], and methysergide injection into the LPBN increases Fos-ir in the NTS and AP, in addition to increasing sodium intake [31,32]. In addition, damage to the CeA reduces the increased sodium intake produced by deactivation of the LPBN inhibitory mechanism [33].…”

“…Brain circuits that control body-fluid balance make anatomical connections with areas that control reward, such as the Acb [12,13]. The Acb also receives projections from putative sodium sensitive cells in the AP, responds with increased Fos-ir to repeated episodes of sodium depletion, and has neuronal excitability modulated by sodium taste or body sodium balance [17][18][19]30]. Moreover, sodium intake in response to single sodium depletion produces Fos-ir in both AcbC and AcSh of non-satiated rats with open gastric fistula [16].…”

Differential effects of mineralocorticoid and angiotensin II on incentive and mesolimbic activity

“…Previous work has implicated this brain system in sodium appetite. For example, the accumbens receives multisynaptic input from aldosterone-sensing and sodium-sensing neurons in the hindbrain (Miller and Loewy, 2014; Shekhtman et al, 2007). Sodium depletion alters the level of dopamine transporters and opioid peptides in the accumbens (Grondin et al, 2011; Lucas et al, 2003; Roitman et al, 1999).…”

Blockade of ENaCs by amiloride induces c-Fos activation of the area postrema

“…Like all CVOs, these structures lack a blood-brain barrier and thus, their neurons and glial cells are continuously exposed to same chemical environment as found in the plasma. On the basis of this anatomical property, we hypothesized that ENaC-expressing CVO neurons may function as plasma sodium sensors since they become c-Fos activated following peripheral manipulations of plasma sodium levels (Miller and Loewy, 2014; Miller et al, 2013). …”

“…Later studies established that serotoninergic AP neurons were c-Fos activated by sodium repletion or hypertonic saline injections (Miller and Loewy, 2014). Some, but not all, of these neurons expressed ENaCs (Miller and Loewy, 2014).…”