Efferent and Afferent Connections of Neuropeptide Y Neurons in the Nucleus Accumbens of Mice

Shunji Yamada,Nienke van Kooten,Takuma Mori,Katsutoshi Taguchi,Atsushi Tsujimura,Masaki Tanaka

doi:10.3389/fnana.2021.741868

Shunji Yamada, Nienke van Kooten + Show 4 more

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https://doi.org/10.3389/fnana.2021.741868

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Abstract

Neuropeptide Y (NPY) is a neural peptide distributed widely in the brain and has various functions in each region. We previously reported that NPY neurons in the nucleus accumbens (NAc) are involved in the regulation of anxiety behavior. Anterograde and retrograde tracing studies suggest that neurons in the NAc project to several areas, such as the lateral hypothalamus (LH) and ventral pallidum (VP), and receive afferent projections from the cortex, thalamus, and amygdala. However, the neural connections between accumbal NPY neurons and other brain areas in mice remain unclear. In this study, we sought to clarify these anatomical connections of NPY neurons in the NAc by investigating their neural outputs and inputs. To selectively map NPY neuronal efferents from the NAc, we injected Cre-dependent adeno-associated viruses (AAVs) into the NAc of NPY-Cre mice. This revealed that NAc NPY neurons exclusively projected to the LH. We confirmed this by injecting cholera toxin b subunit (CTb), a retrograde tracer, into the LH and found that approximately 7–10% of NPY neurons in the NAc were double-labeled for mCherry and CTb. Moreover, retrograde tracing using recombinant rabies virus (rRABV) also identified NAc NPY projections to the LH. Finally, we investigated monosynaptic input to the NPY neurons in the NAc using rRABV. We found that NPY neurons in the NAc received direct synaptic connections from the midline thalamic nuclei and posterior basomedial amygdala. These findings provide new insight into the neural networks of accumbal NPY neurons and should assist in elucidating their functional roles.

Highlights

Neuropeptide Y (NPY) is a neural peptide distributed widely in the brain and is well known for its role in appetite, maintenance of energy homeostasis, and anxiety
We found many dot-like mCherryexpressing fibers in the anterior (Figures 2A,B) and posterior (Figures 2C,D) parts of the lateral hypothalamus (LH) in coronal sections
We found a few mCherryexpressing fibers around the LH, such as the ventral pallidum (VP) and extended amygdala. mCherry-positive cell bodies and fibers were dominant in the nucleus accumbens (NAc) and LH, respectively, demonstrating that NPY neurons in the NAc project to the LH

Summary

Introduction

Neuropeptide Y (NPY) is a neural peptide distributed widely in the brain and is well known for its role in appetite, maintenance of energy homeostasis, and anxiety. We performed time- and region-specific disruption and chemogenetic activation of NPY neurons in the NAc using NPY-Cre mice, which revealed that NAc NPY neurons have a role in reducing anxiety (Yamada et al, 2020). Input and Output of NPY Neurons in the NAc. There are many NPY-positive (Chronwall et al, 1985; Yamada et al, 2020) and NPY mRNA-expressing cells in the NAc (Morris, 1989). There are many NPY-positive (Chronwall et al, 1985; Yamada et al, 2020) and NPY mRNA-expressing cells in the NAc (Morris, 1989). Kawaguchi et al (1995) showed that a subset of GABA and somatostatin double-positive interneurons express NPY in the neostriatum These results suggest that NPY neurons in the NAc are interneurons. Because NPY or NPY receptor type 1 (Y1-R) agonist injection into the NAc did not affect behavioral despair, we proposed that some NPY neurons in the NAc were projection neurons (Aoki et al, 2016)

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