A GABAergic Projection from the Centromedial Nuclei of the Amygdala to Ventromedial Prefrontal Cortex Modulates Reward Behavior

Seo, Dong Oh; Funderburk, Samuel C; Bhatti, Dionnet L.; Motard, Laura E.; Newbold, Dillan J.; Girven, Kasey S.; McCall, Jordan G.; Krashes, Michael J.; Sparta, Dennis R.; Bruchas, Michael R.

doi:10.1523/jneurosci.1164-16.2016

Cited by 65 publications

(58 citation statements)

References 56 publications

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“…Slc32a1/VGat is expressed in inhibitory GABAergic neurons and affects cognitive performance 26 . IHC results demonstrated a significant decrease of VGAT staining (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

Nam

Mounier

Wolfe

et al. 2017

Sci Rep

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We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND). RNA-seq results revealed that in HFD mice there was an increased expression of genes related to immune response, such as Trem2 and Tyrobp. We found a significant increase of TREM2 immunoreactivity in the cortex in response to HFD, most pronounced in female mice that correlated to the amyloid pathology. Down-regulated by HFD were genes related to neuron projections and synaptic transmission in agreement to the significantly deteriorated neurite morphology and cognition in these mice. To examine the effect of the diet on the brain lipidome, we performed Shotgun Lipidomics. While there was no difference in the total amounts of phospholipids of each class, we revealed that the levels of 24 lipid sub-species in the brain were significantly modulated by HFD. Network visualization of correlated lipids demonstrated overall imbalance with most prominent effect on cardiolipin molecular sub-species. This integrative approach demonstrates that HFD elicits a complex response at molecular, cellular and system levels in the CNS.

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“…Slc32a1/VGat is expressed in inhibitory GABAergic neurons and affects cognitive performance 26 . IHC results demonstrated a significant decrease of VGAT staining (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

Nam

Mounier

Wolfe

et al. 2017

Sci Rep

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“…Cell-type specific studies have shown evidence for the involvement of several genetically defined CeA neurons in aversive behaviors such as defensive responses and anxiogenesis (Andero et al, 2014; Han et al, 2015; Haubensak et al, 2010; Isosaka et al, 2015; Li et al, 2013; McCall et al, 2015; Pomrenze et al, 2015; Sanford et al, 2017). However, despite early evidence suggesting the involvement of the CeA in appetitive behaviors (Galaverna et al, 1993; Gallagher et al, 1990; Parkinson et al, 2000; Ritter and Hutton, 1995) and more recent activation studies demonstrating a modulatory role of the CeA in appetitive behaviors (Cai et al, 2014; Robinson et al, 2014; Seo et al, 2016), how appetitive behavior integrates into a structural and functional model of amygdala has yet to be established. For instance, a genetically defined population of CeA neurons that are positive mediators of appetitive behavior has not been identified.…”

Section: Introductionmentioning

confidence: 99%

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Kim

Zhang

Muralidhar

et al. 2017

Neuron

367

493

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Summary Basolateral amygdala (BLA) principle cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here we identified several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissected the BLA to CeA circuit for appetitive behaviors. Protein phosphatase 1 regulatory subunit 1B+ BLA pyramidal neurons to dopamine receptor 1+ CeA neurons define a pathway for promoting appetitive behaviors, while R-spondin 2+ BLA pyramidal neurons to dopamine receptor 2+ CeA neurons define a pathway for suppressing appetitive behaviors. These data reveal genetically defined neural circuits in the amygdala that promote and suppress appetitive behaviors analogous to the direct and indirect pathway of the basal ganglia.

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“…Internal state (affective valence) alters an animal’s ability to assess potential threats and explore different environments, a requirement to locate and consume foods. Therefore, we sought to assess the affective valence of these distinct BNST-PBN circuits by subjecting mice to real-time-place-preference (RTPP) tests and operant-reinforcement assays (Al-Hasani et al, 2015; McCall et al, 2015; Seo et al, 2016). We injected AAV5-EF1α-DIO-ChR2 into the BNST of vGAT-Cre or vGLUT2-Cre mice, placing an optic fiber above the PBN, and tested whether stimulation of this BNST-PBN vGAT pathway was reinforcing or aversive.…”

Section: Resultsmentioning

confidence: 99%

Extended amygdala-parabrachial circuits alter threat assessment to regulate feeding

Bhatti

Pedersen²,

Mulvey³

et al. 2020

Preprint

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29An animal's evolutionary success depends on the ability to seek and consume foods while 30 avoiding environmental threats. However, how evolutionarily conserved threat detection circuits 31 modulate feeding is unknown. In mammals, feeding and threat assessment are strongly 32 influenced by the parabrachial nucleus (PBN), a structure that responds to threats and inhibits 33 feeding. Here, we report that the PBN receives dense inputs from the bed nucleus of the stria 34 terminalis (BNST), an extended amygdala structure that encodes affective information. Using a 35 series of complementary approaches, we identify opposing BNST-PBN circuits that modulate a 36 genetically-defined population of PBN neurons to control feeding. This previously unrecognized 37 neural circuit integrates threat assessment with the intrinsic drive to eat. 38 39 Keywords: extended amygdala; bed nucleus of the stria terminalis; parabrachial nucleus; 40 feeding; threat assessment; anxiety; motivation 41 Main text: 42 43 Introduction 44All animals must successfully seek and consume food while avoiding environmental 45 threats to survive. The internal state of an animal directly impacts the expression of risky 46 behaviors, such as exploring a dangerous environment to obtain rewards and maintain 47 homeostasis. Animals must adaptively prioritize certain behaviors to appropriately respond to their 48 internal state (Alhadeff et al., 2018; Burnett et al., 2016). While many studies have explored the 49 interaction of metabolic need states with behavior, how mammals integrate affective-threat 50 assessment with internal need states remains largely unknown. 51Several recent reports have found that in mammals, food consumption and threat 52 assessment are heavily influenced by the parabrachial nucleus (PBN), a pontine structure that 53 integrates visceral and sensory information to encode metabolic needs (Campos et al., 2016(Campos et al., , 54 2018 Carter et al., 2013; Essner et al., 2017; Han et al., 2015; Mu et al., 2017; Roman et al., 55 2016; Ryan et al., 2017; Zséli et al., 2016). The amygdala and extended amygdala are 56 evolutionarily conserved brain regions that encode and integrate valence, stress, and threat to 57 alter behavioral states. Anatomical data suggest that the PBN receives input from several regions 58 that may encode affective information, including the bed nucleus of the stria terminalis (BNST), a 59 structure in the extended amygdala (Douglass et al., 2017; Kim et al., 2013; Mazzone et al., 2018; 60 Zséli et al., 2016). However, the neural circuit mechanisms that underlie the integration of an 61 animal's own motivation to eat with internal affective states regarding environmental threats are 62 still unknown. Here, we identified two previously unknown afferents from distinct populations 63 within the BNST to the PBN that underlie the complex integration of threat-assessment and 64 feeding signals to modulate PBN activity and ultimately regulate state-dependent feeding. 65 66 67 Results 68 Anatomical and Molecular...

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A GABAergic Projection from the Centromedial Nuclei of the Amygdala to Ventromedial Prefrontal Cortex Modulates Reward Behavior

Cited by 65 publications

References 56 publications

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Extended amygdala-parabrachial circuits alter threat assessment to regulate feeding

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