Role of the lateral parabrachial nucleus in the control of sodium appetite

Abstract

In states of sodium deficiency many animals seek and consume salty solutions to restore body fluid homeostasis. These behaviors reflect the presence of sodium appetite that is a manifestation of a pattern of central nervous system (CNS) activity with facilitatory and inhibitory components that are affected by several neurohumoral factors. The primary focus of this review is on one structure in this central system, the lateral parabrachial nucleus (LPBN). However, before turning to a more detailed discussion of the LPBN, a brief overview of body fluid balance-related body-to-brain signaling and the identification of the primary CNS structures and humoral factors involved in the control of sodium appetite is necessary. Angiotensin II, mineralocorticoids, and extracellular osmotic changes act on forebrain areas to facilitate sodium appetite and thirst. In the hindbrain, the LPBN functions as a key integrative node with an ascending output that exerts inhibitory influences on forebrain regions. A nonspecific or general deactivation of LPBN-associated inhibition by GABA or opioid agonists produces NaCl intake in euhydrated rats without any other treatment. Selective LPBN manipulation of other neurotransmitter systems [e.g., serotonin, cholecystokinin (CCK), corticotrophin-releasing factor (CRF), glutamate, ATP, or norepinephrine] greatly enhances NaCl intake when accompanied by additional treatments that induce either thirst or sodium appetite. The LPBN interacts with key forebrain areas that include the subfornical organ and central amygdala to determine sodium intake. To summarize, a model of LPBN inhibitory actions on forebrain facilitatory components for the control of sodium appetite is presented in this review.

Keywords: angiotensin; electrolyte balance; sodium intake; thirst.

Fig. 1.

Photomicrograph of a coronal section of a rat brain showing the sites of injections into the lateral parabrachial nucleus (LPBN). SCP, superior cerebellar peduncle (outlined); MPBN, medial parabrachial nucleus; LPBN, lateral parabrachial nucleus.

Fig. 2.

Ingestion of 0.3 M NaCl (A) and water (B) induced by intracerebroventricular injection of ANG II (50 ng/1 μl) in rats pretreated with bilateral injections of vehicle (polyethylene glycol/water 2:1) or methysergide (4 μg/0.2 μl) into the LPBN. Results are represented as means ± SE. n = number of rats. *Different from vehicle. From Menani et al. (96).

Fig. 3.

Ingestion of 0.3 M NaCl (A) and water (B) by fluid replete rats treated with bilateral injections of muscimol (0.5 nmol/0.2 μl) or saline combined with injections of vehicle (polyethylene glycol/water 2:1) or bicuculline (GABA_A antagonist, 1.6 nmol/0.2 μl) into the LPBN. Results are represented as means ± SE. n = number of rats. Reprinted from Callera et al. (17) with permission from Elsevier.

Fig. 4.

Schematic diagram based on studies in rats showing the modulation of the LPBN inhibitory mechanism by different neurotransmitters and the interaction between the LPBN inhibitory mechanisms and forebrain facilitatory mechanisms involved in the control of sodium intake.