Lateral Hypothalamic GABAergic Neurons Encode and Potentiate Sucrose's Palatability.

Sucrose is attractive to most species in the animal kingdom, not only because it induces a sweet taste sensation but also for its positive palatability (i.e., oromotor responses elicited by increasing sucrose concentrations). Although palatability is such an important sensory attribute, it is currently unknown which cell types encode and modulate sucrose's palatability. Studies in mice have shown that activation of GABAergic LHAVgat+ neurons evokes voracious eating; however, it is not known whether these neurons would be driving consumption by increasing palatability. Using optrode recordings, we measured sucrose's palatability while VGAT-ChR2 transgenic mice performed a brief access sucrose test. We found that a subpopulation of LHAVgat+ neurons encodes palatability by increasing (or decreasing) their activity as a function of the increment in licking responses evoked by sucrose concentrations. Optogenetic gain of function experiments, where mice were able to choose among available water, 3% and 18% sucrose solutions, uncovered that opto-stimulation of LHAVgat+ neurons consistently promoted higher intake of the most palatable stimulus (18% sucrose). In contrast, if they self-stimulated near the less palatable stimulus, some VGAT-ChR2 mice preferred water over 18% sucrose. Unexpectedly, activation of LHAVgat+ neurons increased quinine intake but only during water deprivation, since in sated animals, they failed to promote quinine intake or tolerate an aversive stimulus. Conversely, these neurons promoted overconsumption of sucrose when it was the nearest stimulus. Also, experiments with solid foods further confirmed that these neurons increased food interaction time with the most palatable food available. We conclude that LHAVgat+ neurons increase the drive to consume, but it is potentiated by the palatability and proximity of the tastant.

Histaminergic modulation of cholinergic release from the nucleus basalis magnocellularis into insular cortex during taste aversive memory formation.

The ability of acetylcholine (ACh) to alter specific functional properties of the cortex endows the cholinergic system with an important modulatory role in memory formation. For example, an increase in ACh release occurs during novel stimulus processing, indicating that ACh activity is critical during early stages of memory processing. During novel taste presentation, there is an increase in ACh release in the insular cortex (IC), a major structure for taste memory recognition. There is extensive evidence implicating the cholinergic efferents of the nucleus basalis magnocellularis (NBM) in cortical activity changes during learning processes, and new evidence suggests that the histaminergic system may interact with the cholinergic system in important ways. However, there is little information as to whether changes in cholinergic activity in the IC are modulated during taste memory formation. Therefore, in the present study, we evaluated the influence of two histamine receptor subtypes, H1 in the NBM and H3 in the IC, on ACh release in the IC during conditioned taste aversion (CTA). Injection of the H3 receptor agonist R-α-methylhistamine (RAMH) into the IC or of the H1 receptor antagonist pyrilamine into the NBM during CTA training impaired subsequent CTA memory, and simultaneously resulted in a reduction of ACh release in the IC. This study demonstrated that basal and cortical cholinergic pathways are finely tuned by histaminergic activity during CTA, since dual actions of histamine receptor subtypes on ACh modulation release each have a significant impact during taste memory formation.

ß-Adrenergic receptors in the insular cortex are differentially involved in aversive vs. incidental context memory formation.

The goal of this research was to determine the effects of ß-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the ß-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition of IA, but had no effect on formation of memory for an inert context (termed incidental memory). These results indicate that IC ß-adrenergic receptors are necessary for memory acquisition of an aversive, but not an inconsequential, context. Nevertheless, subsequent association of a familiar and hitherto inconsequential context with an unconditioned stimulus (US) does require activation of these receptors during its initial acquisition.

Blockade of nucleus basalis magnocellularis or activation of insular cortex histamine receptors disrupts formation but not retrieval of aversive taste memory.

Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical cholinergic activity. Given that cortical cholinergic activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5 microl of pyrilamine (100 mM), an H(1) receptor antagonist, into the NBM, or of R-alpha-methylhistamine (RAMH) (10 mM), an H(3) receptor agonist, into the insular cortex of male Sprague-Dawley rats 20 min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H(1) receptors in NBM or activation of H(3) receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical cholinergic activity modulation during CTA acquisition.