Circumventricular Organs: Integrators of Circulating Signals Controlling Hydration, Energy Balance, and Immune Function

Excerpt

The dominant role of the brain in the hierarchical control of the autonomic nervous system demands that it receive extensive afferent information regarding the “milieu interieur.” This information is derived from two primary sources: (1) peripheral and visceral sensory systems that transmit information through classical sensory pathways into the central nervous system (CNS) and (2) sensory systems in the brain that monitor the constituents of the circulation to assess the physiological status of the individual. However, in view of its protected position behind the blood–brain barrier (BBB), the CNS is theoretically unable to monitor many of the most significant controlled variables that constitute this internal environment (osmolarity, glucose, calcium, lipophobic amino acids, and peptide concentrations). Thus, although the BBB acts to protect the brain from large shifts in these variables (their fine control is a prerequisite for normal CNS function), in theory, it also precludes CNS monitoring of such essential information regarding the physiological status of the internal environment. The logic of such a system is clear, providing the brain can gain access to essential sensory information through alternative mechanisms. A specialized group of CNS structures, which lack the normal BBB, the circumventricular organs (CVOs), provide such an alternative, and they thus play a pivotal role in blood–brain communication. Within these structures, circulating substances can directly influence individual CNS neurons, which—through efferent projections to autonomic control centers in the hypothalamus and medulla (Figure 2.1) —transmit this information for integration leading to appropriate modulation of autonomic outputs, and thus maintenance of “healthy autonomic state.” In addition, considerable recent information suggests that the CVOs sense multiple signals traditionally thought to be of importance in separate physiological systems, including fluid balance (angiotensin II, natriuretic peptides, osmolarity), metabolic control (amylin, ghrelin, leptin), reproduction (relaxin), and immune regulation [interleukin-1 β (IL-1 β), interleukin-6 (IL-6)], although the boundaries delimiting these specific functional roles are rapidly disappearing.

The purpose of this chapter is to consider the potential mechanisms through which single CVO neurons can sense and integrate the critical information from multiple circulating signals of autonomic status. I will specifically describe the literature suggesting that single subfornical organ (SFO) neurons respond to separate signals relaying information regarding body fluid and metabolic status with a focus on nonselective cationic conductances as a site at which such integration may occur. I will first consider some of the primary circulating molecules that provide key sensory information to the CNS in each of these systems.