The contribution of orbitofrontal cortex to stress-related psychiatric disorders: stress induced synaptic change in the orbitofrontal-basolateral amygdala pathway

Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFCàBLA and BLAàlOFC pathways form a functional circuit regulating the encoding (lOFCàBLA) and subsequent use (BLAàlOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

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All That Glitters … Dissociating Attention and Outcome Expectancy From Prediction Errors Signals

Journal of Neurophysiology ◽

10.1152/jn.00173.2010 ◽

2010 ◽

Vol 104 (2) ◽

pp. 587-595 ◽

Cited By ~ 39

Author(s):

Matthew R. Roesch ◽

Donna J. Calu ◽

Guillem R. Esber ◽

Geoffrey Schoenbaum

Keyword(s):

Orbitofrontal Cortex ◽

Basolateral Amygdala ◽

Ventral Striatum ◽

Recent Literature ◽

Neural Correlates ◽

Dopamine Neurons ◽

Outcome Expectancy ◽

Prediction Errors ◽

Signal Prediction ◽

Unexpected Outcomes

Initially reported in dopamine neurons, neural correlates of prediction errors have now been shown in a variety of areas, including orbitofrontal cortex, ventral striatum, and amygdala. Yet changes in neural activity to an outcome or cues that precede it can reflect other processes. We review the recent literature and show that although activity in dopamine neurons appears to signal prediction errors, similar activity in orbitofrontal cortex, basolateral amygdala, and ventral striatum does not. Instead, increased firing in basolateral amygdala to unexpected outcomes likely reflects attention, whereas activity in orbitofrontal cortex and ventral striatum is unaffected by prior expectations and may provide information on outcome expectancy. These results have important implications for how these areas interact to facilitate learning and guide behavior.

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Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala

Neuron ◽

10.1016/s0896-6273(03)00474-4 ◽

2003 ◽

Vol 39 (5) ◽

pp. 855-867 ◽

Cited By ~ 243

Author(s):

Geoffrey Schoenbaum ◽

Barry Setlow ◽

Michael P. Saddoris ◽

Michela Gallagher

Keyword(s):

Orbitofrontal Cortex ◽

Basolateral Amygdala

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Different Roles for Orbitofrontal Cortex and Basolateral Amygdala in a Reinforcer Devaluation Task

Journal of Neuroscience ◽

10.1523/jneurosci.23-35-11078.2003 ◽

2003 ◽

Vol 23 (35) ◽

pp. 11078-11084 ◽

Cited By ~ 220

Author(s):

Charles L. Pickens ◽

Michael P. Saddoris ◽

Barry Setlow ◽

Michela Gallagher ◽

Peter C. Holland ◽

...

Keyword(s):

Orbitofrontal Cortex ◽

Basolateral Amygdala ◽

Reinforcer Devaluation

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Complementary contributions of basolateral amygdala and orbitofrontal cortex to value learning under uncertainty

eLife ◽

10.7554/elife.27483 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 14

Author(s):

Alexandra Stolyarova ◽

Alicia Izquierdo

Keyword(s):

Orbitofrontal Cortex ◽

Basolateral Amygdala ◽

Previous Experience ◽

Wait Times ◽

Meaningful Change ◽

New Learning ◽

Expected Outcome ◽

Value Learning ◽

Expected Outcomes

We make choices based on the values of expected outcomes, informed by previous experience in similar settings. When the outcomes of our decisions consistently violate expectations, new learning is needed to maximize rewards. Yet not every surprising event indicates a meaningful change in the environment. Even when conditions are stable overall, outcomes of a single experience can still be unpredictable due to small fluctuations (i.e., expected uncertainty) in reward or costs. In the present work, we investigate causal contributions of the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) in rats to learning under expected outcome uncertainty in a novel delay-based task that incorporates both predictable fluctuations and directional shifts in outcome values. We demonstrate that OFC is required to accurately represent the distribution of wait times to stabilize choice preferences despite trial-by-trial fluctuations in outcomes, whereas BLA is necessary for the facilitation of learning in response to surprising events.

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Functional and directed connectivity of the cortico-limbic network in mice in vivo

Brain Structure and Function ◽

10.1007/s00429-020-02202-7 ◽

2021 ◽

Author(s):

Zeinab Khastkhodaei ◽

Muthuraman Muthuraman ◽

Jenq-Wei Yang ◽

Sergiu Groppa ◽

Heiko J. Luhmann

Keyword(s):

Functional Connectivity ◽

Psychiatric Disorders ◽

Emotional Regulation ◽

Animal Studies ◽

Basolateral Amygdala ◽

Brain Regions ◽

Therapeutic Interventions ◽

Distinct Frequency ◽

Feedback Connections

AbstractHigher cognitive processes and emotional regulation depend on densely interconnected telencephalic and limbic areas. Central structures of this cortico-limbic network are ventral hippocampus (vHC), medial prefrontal cortex (PFC), basolateral amygdala (BLA) and nucleus accumbens (NAC). Human and animal studies have revealed both anatomical and functional alterations in specific connections of this network in several psychiatric disorders. However, it is often not clear whether functional alterations within these densely interconnected brain areas are caused by modifications in the direct pathways, or alternatively through indirect interactions. We performed multi-site extracellular recordings of spontaneous activity in three different brain regions to study the functional connectivity in the BLA–NAC–PFC–vHC network of the lightly anesthetized mouse in vivo. We show that BLA, NAC, PFC and vHC are functionally connected in distinct frequency bands and determined the influence of a third brain region on this connectivity. In addition to describing mutual synchronicity, we determined the strength of functional connectivity for each region in the BLA–NAC–PFC–vHC network. We find a region-specificity in the strength of feedforward and feedback connections for each region in its interaction with other areas in the network. Our results provide insights into functional and directed connectivity in the cortico-limbic network of adult wild-type mice, which may be helpful to further elucidate the pathophysiological changes of this network in psychiatric disorders and to develop target-specific therapeutic interventions.

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