Sweet and bitter taste stimuli activate VTA projection neurons in the parabrachial nucleus

Abstract

This study investigated neural projections from the parabrachial nucleus (PBN), a gustatory and visceral processing area in the brainstem, to the ventral tegmental area (VTA) in the midbrain. The VTA contains a large population of dopaminergic neurons that have been shown to play a role in reward processing. Anterograde neural tracing methods were first used to confirm that a robust projection from the caudal PBN terminates in the dorsal VTA; this projection was larger on the contralateral side. In the next experiment, we combined dual retrograde tracing from the VTA and the gustatory ventral posteromedial thalamus (VPMpc) with taste-evoked Fos protein expression, which labels activated neurons. Mice were stimulated through an intraoral cannula with sucrose, quinine, or water, and PBN sections were processed for immunofluorescent detection of Fos and retrograde tracers. The distribution of tracer-labeled PBN neurons demonstrated that the populations of cells projecting to the VTA or VPMpc are largely independent. Quantification of cells double labeled for Fos and either tracer demonstrated that sucrose and quinine were equally effective in activating both pathways. These results indicate that information about both appetitive and aversive tastes is delivered to a key midbrain reward interface via direct projections from the PBN.

Satb2 neurons in the parabrachial nucleus mediate taste perception

“…Satb2 is not a comprehensive marker for taste-associated neurons in the PBN, as there are subnuclei containing taste-responsive neurons that do not express Satb2 31 , 37 , 46 . Here we identify a role for CGRP neurons by showing that inactivation of CGRP neurons causes animals to be more accepting of bitter and aversive salt solutions.…”

Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

“…The PBN, which is known for its role in taste regulation (Boughter, Lu, Saites, & Tokita, 2019; Rosen, Victor, & Di Lorenzo, 2011) and appetite suppression (Carter, Soden, Zweifel, & Palmiter, 2013; Wu, Boyle, & Palmiter, 2009; Wu, Clark, & Palmiter, 2012), was notable for the abundance of its input to VTA MC3R neurons (Figure 7). Although the PBN is best known for its projections to the forebrain structures involved in appetite regulation (Herbert, Moga, & Saper, 1990; Karimnamazi, Travers, & Travers, 2002; Ricardo & Koh, 1978), both VTA DA and GABA neurons have been shown to receive direct input from the PBN (Beier et al, 2015; Boughter et al, 2019) including PBN neurons involved in responding to pain, fear, and satiety stimuli (Campos, Bowen, Roman, & Palmiter, 2018; Carter et al, 2013). Additionally, VTA projecting PBN neurons have been shown to be responsive to both sweet and bitter stimuli (Boughter et al, 2019) suggesting that PBN may regulate both reward and aversion‐associated behaviors through its action in the VTA.…”

“…Although the PBN is best known for its projections to the forebrain structures involved in appetite regulation (Herbert, Moga, & Saper, 1990; Karimnamazi, Travers, & Travers, 2002; Ricardo & Koh, 1978), both VTA DA and GABA neurons have been shown to receive direct input from the PBN (Beier et al, 2015; Boughter et al, 2019) including PBN neurons involved in responding to pain, fear, and satiety stimuli (Campos, Bowen, Roman, & Palmiter, 2018; Carter et al, 2013). Additionally, VTA projecting PBN neurons have been shown to be responsive to both sweet and bitter stimuli (Boughter et al, 2019) suggesting that PBN may regulate both reward and aversion‐associated behaviors through its action in the VTA. Further studies will be necessary to determine the role of PBN‐VTA MC3R neuron circuit in feeding, taste, aversion, and reward processing, however.…”

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

“…The VTA has a heterogeneous connectivity (Morales and Margolis, 2017) and a single and monosynaptic circuit responsible for the inhibition DA-neurons through the AM6545-activated vagus nerve cannot be selectively sorted out yet. However, several satiety-related structures in the brainstem, hindbrain and hypothalamus are known to project and modulate, directly or indirectly, VTA DA-neurons (Alhadeff et al, 2012; Boughter et al, 2019; Faget et al, 2016; Grill and Hayes, 2012; Han et al, 2018; Nieh et al, 2016; Wang et al, 2015). Among these circuits, the PBN→VTA relay is of particular interest since excitatory PBN neurons also largely contact VTA GABA-neurons (Beier et al, 2015; Faget et al, 2016) which in turn may drive the inhibition of VTA DA-neurons and consequent dampening of motivated behaviors.…”