The anterior insular cortex associates temporally discontiguous stimuli during threat learning

Learning about potential threats in the environment is indispensable for survival. Deficits in threat learning constitute a key dimension of multiple brain disorders, which include posttraumatic stress disorder and anxiety disorder. While human brain imaging studies have highlighted a reliable engagement of the anterior insular cortex (AIC) in threat learning, its precise role remains elusive partly due to the lack of animal studies that can address causality and mechanistic questions. Filling in this gap, the present mouse study proposes a novel AICmediated mechanism underlying the association of temporally discontiguous stimuli during threat learning. We identified that activity of AIC layer 5 (L5) pyramidal neurons is required for associating temporally discontiguous stimuli, specifically during a time interval between them. Notably, the AIC is not required for associating temporally contiguous stimuli during threat learning. The AIC not only sends the essential information, via its L5 pyramidal neurons, to the basolateral amygdala (BLA) during the time interval, but also receives from the BLA. We also identified a modulatory role of AIC dopamine D1 receptor (D1R)-mediated dopamine signaling in associating temporally discontiguous stimuli during the time interval.

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Chronic Distress in Male Mice Impairs Motivation Compromising Both Effort and Reward Processing With Altered Anterior Insular Cortex and Basolateral Amygdala Neural Activation

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.717701 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lidia Cabeza ◽

Bahrie Ramadan ◽

Stephanie Cramoisy ◽

Christophe Houdayer ◽

Emmanuel Haffen ◽

...

Keyword(s):

Decision Making ◽

Basolateral Amygdala ◽

Insular Cortex ◽

Brain Regions ◽

Reward Processing ◽

Postmortem Brain ◽

Decision Making Under Uncertainty ◽

Neural Activation ◽

Male Mice ◽

Anterior Insular Cortex

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contributes to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward-processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from novelty suppressed feeding, operant effort-based choice, free feeding, and sucrose preference tasks) collectively show that behavioural initiation, effort allocation, and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlights CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how effort and reward processing contribute to adjust the motivational threshold triggering goal-directed behaviours in versatile environments.

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Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala orchestrates aversive taste memory retrieval

10.1101/2021.03.01.433377 ◽

2021 ◽

Author(s):

Adonis Yiannakas ◽

Sailendrakumar Kolatt Chandran ◽

Haneen Kayyal ◽

Nathaniel Gould ◽

Mohammad Khamaisy ◽

...

Keyword(s):

Memory Retrieval ◽

Basolateral Amygdala ◽

Pyramidal Neurons ◽

Insular Cortex ◽

Anterior Insula ◽

Inhibitory Synapses ◽

List Type ◽

Synaptic Inhibition ◽

Aversive Taste ◽

Parvalbumin Interneuron

AbstractMemory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. While memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that aversive taste memory retrieval promotes cell-type-specific activation in the aIC. Aversive, but not appetitive taste memory retrieval, relies on specific changes in activity and connectivity at parvalbumin (PV) inhibitory synapses onto aIC pyramidal neurons projecting to the basolateral amygdala. PV aIC interneurons, coordinate aversive taste memory retrieval, and are necessary for its dominance when conflicting internal representations are encountered. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival.Graphical AbstractRetrieval of Conditioned Taste Aversion (CTA) memories at the anterior insular cortex activates Parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA).Unlike innately appetitive taste memory retrieval, CTA retrieval increases the amplitude and frequency of synaptic inhibition onto aIC-BLA projecting neurons, that is dependent on activity in aIC PV interneurons.Activation of aIC PV interneurons is necessary for the expression of learned taste avoidance, in both sexes, regardless of stimulus identity.Extinction of aversive taste memories suppresses the frequency, but not the amplitude of synaptic inhibition on aIC-BLA projecting neurons.The reinstatement of aversive taste memories following extinction is dependent upon activation of aIC PV interneurons and increases in the frequency of inhibition on aIC-BLA projecting neurons.

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Glutamatergic basolateral amygdala to anterior insular cortex circuitry maintains rewarding contextual memory

Communications Biology ◽

10.1038/s42003-020-0862-z ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Elvi Gil-Lievana ◽

Israela Balderas ◽

Perla Moreno-Castilla ◽

Jorge Luis-Islas ◽

Ross A. McDevitt ◽

...

Keyword(s):

Basolateral Amygdala ◽

Insular Cortex ◽

Contextual Memory ◽

Anterior Insular Cortex

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Chronic distress in male mice impairs motivation compromising both effort and reward processing with altered anterior insular cortex and basolateral amygdala neural activation

10.1101/2021.05.28.446144 ◽

2021 ◽

Author(s):

Lidia Cabeza ◽

Bahrie Ramadan ◽

Stephanie Cramoisy ◽

Christophe Houdayer ◽

Emmanuel Haffen ◽

...

Keyword(s):

Decision Making ◽

Basolateral Amygdala ◽

Insular Cortex ◽

Brain Regions ◽

Reward Processing ◽

Postmortem Brain ◽

Decision Making Under Uncertainty ◽

Neural Activation ◽

Male Mice ◽

Anterior Insular Cortex

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contribute to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from Novelty Supressed Feeding, operant effort-based choice, Free Feeding and Sucrose Preference tasks) collectively show that behavioural initiation, effort allocation and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlight a CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in cue appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how the stoichiometry of effort and reward processing contributes to dynamically adjust the motivational threshold triggering goal-directed behaviours in versatile environments.

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