Hypothetical Roles of the Olfactory Tubercle in Odor-Guided Eating Behavior

Abstract

Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of activated glomeruli in the olfactory bulb, which is referred to as the odor map. However, the functional roles of the olfactory cortex, a collective region that receives axonal projections from the olfactory bulb, and higher olfactory centers in odor-guided eating behaviors are yet to be elucidated. The olfactory tubercle (OT) is a component of the ventral striatum and forms a node within the mesolimbic dopaminergic pathway. Recent studies have revealed the anatomical domain structures of the OT and their functions in distinct odor-guided motivated behaviors. Another component of the ventral striatum, the nucleus accumbens, is well known for its involvement in motivation and hedonic responses for foods, which raises the possibility of functional similarities between the OT and nucleus accumbens in eating. This review first summarizes recent findings on the domain- and neuronal subtype-specific roles of the OT in odor-guided motivated behaviors and then proposes a model for the regulation of eating behaviors by the OT.

Keywords: attractive behavior; aversive behavior; dopamine; eating; motivation; olfaction; olfactory tubercle; palatability.

FIGURE 1

Cytoarchitectonically defined-domains of the mouse olfactory tubercle (OT). (A–C) In situ hybridization for dopamine receptor D1 (Drd1, A,C) and D2 (Drd2, B) mRNA in the anterior OT of mouse counterstained with Nuclear Fast Red. c-fos expression mapping revealed that D1 receptor-expressing neurons in the anteromedial OT were activated by sugar-associated cue odors, which accompanied attractive behavior (A) and that D1 receptor-expressing neurons in the lateral OT (A) and D2 receptor-expressing neurons in the anteromedial OT (B) were activated by electrical shock-associated cue odors which accompanied aversive behavior. In the cap regions (arrows), the dwarf cells are densely packed and express Drd1 but not Drd2 mRNA (B,C). The granule cells in the Islands of Calleja (arrowheads) are also densely packed but exhibit weak expression of Drd1 and no Drd2 mRNA (B,C). Medium spiny neurons are mainly distributed in the layer II of the cortex-like regions, which are interposed between the cap regions and Islands of Calleja in these coronal sections, and express either Drd1 or Drd2 (A,B). The cap region and Islands of Calleja serve as anatomical landmarks for the lateral and medial domains of the OT, respectively. ICj, Islands of Calleja; D, dorsal; V, ventral; M, medial; L, lateral. The Figures are modified from (Murata et al., 2015).

FIGURE 2

A hypothetical model of the OT and eating. The OT receives and may integrate olfactory inputs and feeding-related hormonal signals, as well as other sensory modalities, visceral, and neuromodulatory inputs. The hypothesis is that activation of the D1 receptor-expressing neurons in the anteromedial OT increases food intake, whereas activation of the D2 receptor-expressing neurons in the anteromedial OT and D1 receptor-expressing neurons in the lateral OT decreases food intake based on their involvement in attractive and aversive behaviors, respectively. Feeding-related hormonal signals, such hunger and satiety, may regulate the activity of OT neurons in a domain- and cell type-specific manner. These signals result in homeostatic evaluation, motivation, and hedonic responses to food odors and flavors. D1 and D2 receptor-expressing neurons in layer II of the cortex-like region were noted to be intermingled in both the anteromedial and lateral OT domains, as shown in Figure 1 but simplified here in this figure. Red circles, D1 receptor-expressing medium spiny neurons in layer II of cortex-like regions and dwarf cells in the cap regions (arrows); blue circles, D2 receptor-expressing medium spiny neurons in layer II of cortex-like regions; gray circles, granule cells in the Islands of Calleja (arrowheads). Pir, piriform cortex; NAc, nucleus accumbens; VP, ventral pallidum; ICj, Islands of Calleja. D, dorsal; V, ventral; M, medial; L, lateral. Stereotaxic atlas from Paxinos and Franklin (2008).