Seeking motivation and reward: Roles of dopamine, hippocampus, and supramammillo-septal pathway

Kesner, Andrew J.; Calva, Coleman B.; Ikemoto, Satoshi

doi:10.1016/j.pneurobio.2022.102252

Cited by 15 publications

(6 citation statements)

References 192 publications

(257 reference statements)

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“…We also measured the highest number of VGLUT2 + neurons in anterior sections where subregions IF and RLi first appear (Figure 5A). Indeed, an abundance of VGLUT2 + neurons are present just anterior to these medial subregions, for example in supramammillary nucleus (Kesner et al, 2022). There is an analogous abundance of GABA neurons in structures caudal to VTA such as in RMTg (Jhou, 2005), or ventral to SNc in SNr.…”

Section: Discussionmentioning

confidence: 99%

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta

Conrad,

Oriol,

Kollman

et al. 2024

Preprint

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Most studies on the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) have focused on dopamine neurons and their role in processes such as motivation, learning, movement, and associated disorders. However there has been increasing attention on other VTA and SNc cell types that release GABA, glutamate, or a combination of these neurotransmitters. Yet the relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc has remained unclear. Here, we used fluorescent in situ hybridization in male and female mice to label VTA and SNc neurons that expressed mRNA encoding the canonical vesicular transporters for dopamine, GABA, or glutamate: vesicular monoamine transporter VMAT2, vesicular GABA transporter (VGAT), and vesicular glutamate transporter (VGLUT2). Within VTA, we found that no one type was particularly more abundant, instead we observed similar numbers of VMAT2+ (44%), VGAT+ (37%) and VGLUT2+ (41%) neurons. In SNc we found that a slight majority of neurons expressed VMAT2 (54%), fewer were VGAT+ (42%), and VGLUT2+ neurons were least abundant (16%). Moreover, 20% of VTA neurons and 10% of SNc neurons expressed more than one vesicular transporter, including 45% of VGLUT2 neurons. We also assessed within VTA and SNc subregions and found remarkable heterogeneity in cell-type composition. And by quantifying density across both anterior-posterior and medial-lateral axes we generated heatmaps to visualize the distribution of each cell type. Our data complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc than is typically appreciated.

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Section: Discussionmentioning

confidence: 99%

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta

Conrad,

Oriol,

Kollman

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“… 22 The training hypothesis postulates that recurrent patterns of neural excitation serve as a form of neural “conditioning,” aiding in overcoming hurdles that impede the translation of learned knowledge into behavior. 23 , 24 The threshold hypothesis proposes that a certain degree or threshold of neural excitation is a prerequisite for cognitive enhancement. 25 Finally, the specificity hypothesis asserts that particular subsets of neurons or their connections within the VTA–hippocampal dopaminergic pathway are vital for cognitive enhancement.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals

Tamatsu,

Azechi,

Takahashi

et al. 2023

iScience

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“…DA is well known for modulating appetitive and aversive motivational processes through binding to D1Rs or D2Rs ( Salamone and Correa 2012 ; Kesner et al 2022 ). For social dominance, van der Kooij et al (2018) found that intra-NAC infusion of a D1R antagonist abolishes the animals’ chances to become dominant; Shan et al (2022) found that chemogenetic activation of D1R-expressing neurons in the NAC shell reduces social dominance, while chemogenetic activation of D2R-expressing neurons in the NAC core promotes social dominance in mice; and Yamaguchi et al (2017) found that systemic administration of a D2R but not a D1R antagonist attenuated social dominance in both mice and macaques.…”

Section: Discussionmentioning

confidence: 99%

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice

Song

et al. 2022

Current Zoology

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Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DRs-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after one week of cohabitation. Lower-rank individuals showed social anxiety together with decreased serum testosterone levels. D2Rs expression were significantly down-regulated in the dorsal part of mPFC (dmPFC) in lower-rank individuals, whereas D1Rs expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2Rs activation in the subordinates and D2Rs inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

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Seeking motivation and reward: Roles of dopamine, hippocampus, and supramammillo-septal pathway

Cited by 15 publications

References 192 publications

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta

Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice

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