An insula-central amygdala circuit for behavioral inhibition

AbstractPredicting which substances are suitable for consumption during foraging is critical for animals to survive. While food-seeking behavior is extensively studied, the neural circuit mechanisms underlying avoidance of potentially poisonous substances remain poorly understood. Here we examined the role of the insular cortex (IC) to central amygdala (CeA) circuit in the establishment of such avoidance behavior. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the “no-go” response, while leaving the “go” response largely unaffected in a tastant (sucrose/quinine)-reinforced “go/no-go” task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activity in the IC-CeL circuit is necessary for establishing anticipatory avoidance responses to an aversive tastant, and is also sufficient to drive learning of such anticipatory avoidance. This function of the IC-CeL circuit is likely important for guiding avoidance of substances with unpleasant tastes during foraging in order to minimize the chance of being poisoned.Significance StatementThe ability to predict which substances are suitable for consumption is critical for survival. Here we found that activity in the insular cortex (IC) to central amygdala (CeA) circuit is necessary for establishing avoidance responses to an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for behavioral inhibition in anticipation of potentially poisonous substances during foraging.

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Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats

Psychopharmacology ◽

10.1007/s00213-017-4632-7 ◽

2017 ◽

Vol 234 (16) ◽

pp. 2431-2441 ◽

Cited By ~ 15

Author(s):

Amy A. Arguello ◽

Rong Wang ◽

Carey M. Lyons ◽

Jessica A. Higginbotham ◽

Matthew A. Hodges ◽

...

Keyword(s):

Insular Cortex ◽

Contextual Control ◽

Cocaine Seeking ◽

Seeking Behavior

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A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding

Nature Communications ◽

10.1038/s41467-020-19980-7 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

B. Sofia Beas ◽

Xinglong Gu ◽

Yan Leng ◽

Omar Koita ◽

Shakira Rodriguez-Gonzalez ◽

...

Keyword(s):

Ventrolateral Medulla ◽

Cellular Mechanisms ◽

Posterior Portion ◽

Functional Connections ◽

Midline Thalamus ◽

Anatomical Imaging ◽

Seeking Behavior ◽

Catecholamine Neurons ◽

Food Seeking

AbstractMarked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLMCA neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLMCA neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLMCA projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLMCA–pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLMCA–pPVT–NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.

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The role of different subregions of the basolateral amygdala in cue-induced reinstatement and extinction of food-seeking behavior

Neuroscience ◽

10.1016/j.neuroscience.2007.03.025 ◽

2007 ◽

Vol 146 (4) ◽

pp. 1484-1494 ◽

Cited By ~ 43

Author(s):

R.J. McLaughlin ◽

S.B. Floresco

Keyword(s):

Basolateral Amygdala ◽

Seeking Behavior ◽

Food Seeking

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The Dorsal Agranular Insular Cortex Regulates the Cued Reinstatement of Cocaine-Seeking, but not Food-Seeking, Behavior in Rats

Neuropsychopharmacology ◽

10.1038/npp.2015.92 ◽

2015 ◽

Vol 40 (10) ◽

pp. 2425-2433 ◽

Cited By ~ 31

Author(s):

Caitlin V Cosme ◽

Andrea L Gutman ◽

Ryan T LaLumiere

Keyword(s):

Insular Cortex ◽

Cocaine Seeking ◽

Seeking Behavior ◽

Food Seeking

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NTS and VTA oxytocin reduces food motivation and food seeking

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00201.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. R673-R683 ◽

Cited By ~ 1

Author(s):

Hallie S. Wald ◽

Ananya Chandra ◽

Anita Kalluri ◽

Zhi Yi Ong ◽

Matthew R. Hayes ◽

...

Keyword(s):

Food Intake ◽

Nucleus Tractus Solitarius ◽

Progressive Ratio ◽

Food Motivation ◽

Inhibitory Effects ◽

Self Administration ◽

Seeking Behavior ◽

Operant Reinforcement ◽

Food Seeking

Oxytocin (OT) is a neuropeptide whose central receptor-mediated actions include reducing food intake. One mechanism of its behavioral action is the amplification of the feeding inhibitory effects of gastrointestinal (GI) satiation signals processed by hindbrain neurons. OT treatment also reduces carbohydrate intake in humans and rodents, and correspondingly, deficits in central OT receptor (OT-R) signaling increase sucrose self-administration. This suggests that additional processes contribute to central OT effects on feeding. This study investigated the hypothesis that central OT reduces food intake by decreasing food seeking and food motivation. As central OT-Rs are expressed widely, a related focus was to assess the role of one or more OT-R-expressing nuclei in food motivation and food-seeking behavior. OT was delivered to the lateral ventricle (LV), nucleus tractus solitarius (NTS), or ventral tegmental area (VTA), and a progressive ratio (PR) schedule of operant reinforcement and an operant reinstatement paradigm were used to measure motivated feeding behavior and food-seeking behavior, respectively. OT delivered to the LV, NTS, or VTA reduced 1) motivation to work for food and 2) reinstatement of food-seeking behavior. Results provide a novel and additional interpretation for central OT-driven food intake inhibition to include the reduction of food motivation and food seeking.

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12. Relapse to Methamphetamine Seeking After Choice-Based Voluntary Abstinence (Contingency Management): Role of Central Amygdala and Anterior Insular Cortex

Biological Psychiatry ◽

10.1016/j.biopsych.2018.02.029 ◽

2018 ◽

Vol 83 (9) ◽

pp. S5

Author(s):

Marco Venniro ◽

Daniele Caprioli ◽

Michelle Zhang ◽

Leslie Whitaker ◽

Shiling Zhang ◽

...

Keyword(s):

Contingency Management ◽

Insular Cortex ◽

Central Amygdala ◽

Anterior Insular Cortex

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Hunger as a Context: Food Seeking That Is Inhibited During Hunger Can Renew in the Context of Satiety

Psychological Science ◽

10.1177/0956797617719084 ◽

2017 ◽

Vol 28 (11) ◽

pp. 1640-1648 ◽

Cited By ~ 15

Author(s):

Scott T. Schepers ◽

Mark E. Bouton

Keyword(s):

Behavioral Inhibition ◽

Basic Research ◽

Conditioning Context ◽

Motivated Behavior ◽

Potential Reason ◽

Fatty Food ◽

Treatment Context ◽

Food Seeking

At the end of a diet, even a successful one, people often return to overeating. One potential reason is that the behavioral inhibition that people learn while dieting might not readily transfer outside the context in which it is learned: Basic research indicates that after a behavior is inhibited, a return to the conditioning context or simple removal from the treatment context can cause the behavior to return (i.e., to renew). Can states of hunger and satiety play the role of context? In two experiments, rats learned a food-seeking response that earned sucrose or sweet, fatty food pellets while they were satiated. Responding was then inhibited (i.e., extinguished) while the rats were hungry. On the rats’ return to the satiated state, their food seeking was renewed. Additional results suggest that associations with hunger or satiety stimuli were learned more readily than associations with other potentially useful exteroceptive stimuli. The findings have implications for understanding the role of interoceptive contexts in controlling the inhibition of motivated behavior.

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Discriminative stimuli are sufficient for incubation of cocaine craving

eLife ◽

10.7554/elife.44427 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 2

Author(s):

Rajtarun Madangopal ◽

Brendan J Tunstall ◽

Lauren E Komer ◽

Sophia J Weber ◽

Jennifer K Hoots ◽

...

Keyword(s):

Relapse Prevention ◽

Neural Mechanisms ◽

Drug Addicts ◽

Palatable Food ◽

Discriminative Stimuli ◽

Cocaine Craving ◽

Seeking Behavior ◽

Food Seeking ◽

Over Time

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency (‘incubate’) over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds promise for drug relapse treatments.

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