Limbic control over the homeostatic need for sodium

Abstract

The homeostatic need for sodium is one of the strongest motivational drives known in animals. Although the brain regions involved in the sensory detection of sodium levels have been mapped relatively well, data about the neural basis of the motivational properties of salt appetite, including a role for midbrain dopamine cells, have been inconclusive. Here, we employed a combination of fiber photometry, behavioral pharmacology and c-Fos immunohistochemistry to study the involvement of the mesocorticolimbic dopamine system in salt appetite in rats. We observed that sodium deficiency affected the responses of dopaminergic midbrain neurons to salt tasting, suggesting that these neurons encode appetitive properties of sodium. We further observed a significant reduction in the consumption of salt after pharmacological inactivation of the nucleus accumbens (but not the medial prefrontal cortex), and microstructure analysis of licking behavior suggested that this was due to decreased motivation for, but not appreciation of salt. However, this was not dependent on dopaminergic neurotransmission in that area, as infusion of a dopamine receptor antagonist into the nucleus accumbens did not alter salt appetite. We conclude that the nucleus accumbens, but not medial prefrontal cortex, is important for the behavioral expression of salt appetite by mediating its motivational component, but that the switch in salt appreciation after sodium depletion, although detected by midbrain dopamine neurons, must arise from other areas.

Investigating the Effect of Physiological Need States on Palatability and Motivation Using Microstructural Analysis of Licking

“…More recently, Verharen, et al (2019), using a long pause criterion to define episodes of licking (see above), reported a general trend towards sodium depletion increasing cluster number and cluster size. Moreover, sodium depletion also appeared to increase water intake during the same consumption test, but this later effect was only driven by an increase in the number of clusters and not cluster size.…”

“…The study by Verharen, et al (2019), discussed in the above section, is a notable exception as they studied water intake in rats with and without 7-h water restriction. Water restriction was observed to increase the number of drinking bouts without affecting their size, although it should be noted that the analysis parameters used here differed from those conventionally used in lick microstructure studies.…”

Dopaminergic contributions to behavioral control under threat of punishment in rats

“…Sections (approximately + 1.5 mm Bregma for VS and + 3.7-4.2 mm Bregma for vmPFC) were photographed using a brightfield microscope (at a × 5 magnification; AxioImager M2), and c-Fos analysis was performed in a semi-automated fashion using an ImageJ (Version 1.51s) routine (Verharen et al 2019a). First, the microscopic images were Fouriertransformed, and a band-pass filter was applied, band-pass filtering structures of approximately the size of c-Fos-expressing nuclei (filter was set between 3 and 6 pixels).…”

Computational Mechanisms of Osmoregulation: A Reinforcement Learning Model for Sodium Appetite

“…For instance, the activity of dopaminergic neurons in the VTA, which is thought to exhibit a robust relationship with the RL process in the brain ( Nakanishi et al, 2014 ; Schultz, 2015 ), increases when sodium-depleted mice lick saltwater. In contrast, pharmacological inactivation of neural projections from the VTA to the nucleus accumbens decreases sodium intake ( Verharen et al, 2019 ). In addition, recent studies have indicated that optogenetic excitation of VTA dopaminergic neurons suppresses sodium intake in sodium-depleted mice ( Sandhu et al, 2018 ).…”

“…For example, activation of dopaminergic neurons in the ventral tegmental area (VTA), which exhibit robust correlations with reward systems, decreases salt intake ( Sandhu et al, 2018 ). Recent evidence also indicates that dopaminergic neurons in the midbrain may encode appetitive properties of sodium ( Verharen et al, 2019 ) and reward prediction error ( Cone et al, 2016 ), while some excitatory neurons in the pre-locus coeruleus decrease sodium appetite ( Lee et al, 2019 ). Conversely, the activation of neurons in the subfornical organ has been shown to increase sodium appetite ( Matsuda et al, 2017 ).…”