The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area

Gordon-Fennell, Adam; Will, Ryan G.; Ramachandra, Vorani; Gordon-Fennell, Lydia; Domínguez, Juan M.; Zahm, Daniel S.; Marinelli, Michela

doi:10.3389/fnins.2019.01433

Cited by 18 publications

(22 citation statements)

References 74 publications

(97 reference statements)

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“…VP DREADD expression was mostly localized within strictly-defined VP borders here, though in most rats at least some expression encroached upon nearby subcortical structures containing GABAergic neurons with important behavioral roles (Koob, 2004; Silberman et al, 2009; Jennings et al, 2013; Barker et al, 2017; Saga et al, 2017; Gordon-Fennell et al, 2020), so we cannot definitively exclude overlapping roles for these neurons in behavioral effects.…”

Section: Discussionmentioning

confidence: 80%

Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice

Farrell¹,

Esteban²,

Faget³

et al. 2020

Preprint

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Pursuing rewards while avoiding danger is an essential function of nervous systems. Here, we examine a new mechanism helping rats negotiate the balance between risk and reward when making high-stakes decisions. Specifically, we focus on GABA neurons within an emerging mesolimbic circuit nexus, the ventral pallidum (VP). These neurons play a distinct role from other VP neurons in simple motivated behaviors in mice, but their roles in more complex motivated behaviors is unknown. Here, we interrogate the behavioral functions of VP GABA neurons in male and female transgenic GAD1:Cre rats (and wildtype littermates), using reversible chemogenetic inhibition. Employing a behavioral assay of risky decision making, and of the food-seeking and shock-avoidance components of this task, we show that engaging inhibitory Gi/o signaling specifically in VP GABA neurons suppresses motivation to pursue highly salient palatable foods, and notably, also motivation to avoid being shocked. In contrast, inhibiting these neurons did not affect seeking of low-value food, or free consumption even of palatable food, nor did it impact unconditioned affective responses to shock. Accordingly, when rats considered whether to pursue food despite potential for shock in a risky decision-making task, inhibiting VP GABA neurons caused rats to more readily select a small but safe reward over a large but dangerous one--the first demonstration of a VP role in complex decision making. Together, results indicate that VP GABA neurons are critical for high-stakes adaptive responding that is necessary for life, but which might also malfunction in psychiatric disease.

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Section: Discussionmentioning

confidence: 80%

Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice

Farrell¹,

Esteban²,

Faget³

et al. 2020

Preprint

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“…We recently observed that LPO glutamate and GABA neurons play opposing roles in driving motivated behavior, at least in their projections to the lateral habenula, with the activation of GABAergic neurons producing reward and the activation of glutamatergic neurons driving aversion (Barker et al, 2017). Moreover, a recent study observed similar kinds of opposing responses in LPO projections to the ventral tegmental area (Gordon-Fennell et al, 2019). The opposing neuronal subtypes we observed during self-administration may represent a coordinated but opposing response by LPO glutamate and GABA neurons.…”

Section: Discussionmentioning

confidence: 93%

“…Our findings also indicate that only a subset of LPO neurons participate in signaling during cocaine self-administration. It would therefore be of great interest for future studies to examine whether these responsive ensembles comprise a specific cell-type or project to a particular structure; projections to the LHb (Barker et al, 2017), VTA (Gordon-Fennell et al, 2020;Gordon-Fennell et al, 2019), or RMTG (Yetnikoff et al, 2015) are all compelling targets. Additionally, with the recent finding that the LPO may play an important role in drug relapse and decision making during relapse (Gordon-Fennell et al, 2020), more work is needed to determine the roles of specific LPO neuronal subtypes in supporting drug-seeking behavior.…”

Section: Discussionmentioning

confidence: 99%

Lateral Preoptic Area Neurons Signal Cocaine Self-Administration Behaviors

Coffey

Venkat

West

et al. 2021

Preprint

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The lateral preoptic area is implicated in numerous aspects of substance use disorder. In particular, the lateral preoptic area is highly sensitive to the pharmacological properties of psychomotor stimulants, and its activity promotes drug-seeking in the face of punishment and reinstatement during abstinence. Despite the lateral preoptic areas complicity in substance use disorder, how precisely lateral preoptic area neurons encode the individual components of drug self-administration has not been ascertained. To bridge this gap, we examined how the firing of single lateral preoptic area neurons correlates with three discrete elements of cocaine self-administration: 1) drug-seeking (pre-response), 2) drug-taking (response), and 3) receipt of the cocaine infusion. A significant subset of lateral preoptic area neurons responded to each component with a mix of increases and decreases in firing-rate. A majority of these neurons encoded the operant response with increases in spiking, though responses during the drug-seeking, taking, and reciept windows were highly correlated.

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“…Rats were trained to self‐administer meth in operant chambers equipped with two “nose‐poke” holes, a stimulus light above each hole, an audio tone generator and a house light. Nose‐poking is an ethologically relevant behavior and a commonly employed operant task with rodents (e.g., Brown et al., 2020; Chen et al., 2020; Fredriksson et al., 2019; Gordon‐Fennell et al., 2019; Hong, Kang, Chen, & Choi, 2019; Oliva & Wanat, 2019). Each operant chamber was enclosed in a ventilated, sound‐attenuating chamber.…”

Section: Methodsmentioning

confidence: 99%

Hippocampal blood–brain barrier of methamphetamine self‐administering HIV‐1 transgenic rats

Ohene‐Nyako

Persons

Napier

2020

Eur J of Neuroscience

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Combined antiretroviral therapy for HIV infection reduces plasma viral load and prolongs life. However, the brain is a viral reservoir, and pathologies such as cognitive decline and blood–brain barrier (BBB) disruption persist. Methamphetamine abuse is prevalent among HIV‐infected individuals. Methamphetamine and HIV toxic proteins can disrupt the BBB, but it is unclear if there exists a common pathway by which HIV proteins and methamphetamine induce BBB damage. Also unknown are the BBB effects imposed by chronic exposure to HIV proteins in the comorbid context of chronic methamphetamine abuse. To evaluate these scenarios, we trained HIV‐1 transgenic (Tg) and non‐Tg rats to self‐administer methamphetamine using a 21‐day paradigm that produced an equivalency dose range at the low end of the amounts self‐titrated by humans. Markers of BBB integrity were measured for the hippocampus, a brain region involved in cognitive function. Outcomes revealed that tight junction proteins, claudin‐5 and occludin, were reduced in Tg rats independent of methamphetamine, and this co‐occurred with increased levels of lipopolysaccharide, albumin (indicating barrier breakdown) and matrix metalloproteinase‐9 (MMP‐9; indicating barrier matrix disruption); reductions in GFAP (indicating astrocytic dysfunction); and microglial activation (indicating inflammation). Evaluations of markers for two signaling pathways that regulate MMP‐9 transcription, NF‐κB and ERK/∆FosB revealed an overall genotype effect for NF‐κB. Methamphetamine did not alter measurements from Tg rats, but in non‐Tg rats, methamphetamine reduced occludin and GFAP, and increased MMP‐9 and NF‐κB. Study outcomes suggest that BBB dysregulation resulting from chronic exposure to HIV‐1 proteins or methamphetamine both involve NF‐κB/MMP‐9.

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The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area

Cited by 18 publications

References 74 publications

Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice

Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice

Lateral Preoptic Area Neurons Signal Cocaine Self-Administration Behaviors

Hippocampal blood–brain barrier of methamphetamine self‐administering HIV‐1 transgenic rats

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