Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances the learning of cue-reward contingency

Crouse, Richard B.; Kim, Kristen K.O.; Batchelor, Hannah M; Girardi, Eric; Kamaletdinova, Rufina; Chan, Justin; Rajebhosale, Prithviraj; Pittenger, Steven T.; Role, Lorna W.; Talmage, David A.; Jing, Miao; Li, Yulong; Gao, Xiao-Bing; Mineur, Yann S.; Picciotto, Marina R.

doi:10.7554/elife.57335

Cited by 78 publications

(86 citation statements)

References 64 publications

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“…BLA neurons were found to be robustly activated at the time of stimulus-reward pairing as well as at cue onset, consistent with prior evidence that the BLA is activated by both rewards (Crouse et al, 2020;Fontanini et al, 2009;Malvaez et al, 2019;Roesch et al, 2010;Schoenbaum et al, 1998a;Sugase-Miyamoto & Richmond, 2005) and their predictors (Belova et al, 2008;Beyeler et al, 2018;Beyeler et al, 2016;Crouse et al, 2020;Lutas et al, 2019;Malvaez et al, 2015;Muramoto et al, 1993;Paton et al, 2006;Schoenbaum et al, 1998aSchoenbaum et al, , 1999Sugase-Miyamoto & Richmond, 2005;Tye & Janak, 2007;Tye et al, 2008). Interestingly, the cues triggered a transient elevation in BLA activity at their onset, rather than a sustained elevation throughout their 2-min duration, perhaps suggesting that such activity reflects the state change, rather than the state per se.…”

Section: Discussionsupporting

confidence: 84%

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Sias

Morse

Wang

et al. 2021

eLife

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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.

show abstract

Section: Discussionsupporting

confidence: 84%

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Sias

Morse

Wang

et al. 2021

eLife

View full text Add to dashboard Cite

show abstract

“…BLA neurons were found to be robustly activated at the time of stimulus-reward pairing as well as at stimulus onset, consistent with prior evidence that the BLA is activated by both rewards (Crouse et al, 2020;Fontanini et al, 2009;Malvaez et al, 2019;Roesch et al, 2010;Schoenbaum et al, 1998a;Sugase-Miyamoto & Richmond, 2005) and their predictors (Belova et al, 2008;Beyeler et al, 2018;Beyeler et al, 2016;Crouse et al, 2020;Lutas et al, 2019;Malvaez et al, 2015;Muramoto et al, 1993;Paton et al, 2006;Schoenbaum et al, 1998aSchoenbaum et al, , 1999Sugase-Miyamoto & Richmond, 2005;Tye & Janak, 2007;Tye et al, 2008). Interestingly, the cues triggered a transient elevation in BLA activity at their onset, rather than a sustained elevation throughout their 2-min duration, perhaps suggesting that such activity reflects the state change, rather than the state per se.…”

Section: Discussionsupporting

confidence: 84%

“…Thus, cue-induced BLA activation later in training reflects appetitive associative learning. Whereas we detected reward responses throughout training, prior data have demonstrated a shift in BLA responses from the reward to predictive events (Crouse et al, 2020) and little response to rewards in the absence of learning (Malvaez et al, 2015). The persistent reward response detected here likely results from the uncertainty of reward timing during the cues, which, rather than being deterministic, set the context for the intermittent availability of one specific reward.…”

Section: Discussioncontrasting

confidence: 64%

“…It was surprising that responses to the cues were present on the first conditioning session, particularly in light of evidence that BLA cue responses to both appetitive and aversive cues increase across learning (Crouse et al, 2020;Johansen et al, 2010;Lutas et al, 2019;Tye et al, 2008). This could reflect a nonassociative, novelty response to either or both the tone or noise presentation.…”

Section: Bla Neurons Respond To Rewards and Cues During Appetitive Pamentioning

confidence: 99%

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A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Sias¹,

Morse²,

Wang³

et al. 2021

Preprint

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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 an 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 that 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 to perform a serial circuit disconnection, we found that activity in lOFC→BLA projections regulates the encoding of the same components of the stimulus-outcome memory that are later used to allow cues to guide choice via activity in BLA→lOFC projections. Thus, the lOFC→BLA→lOFC circuit regulates the encoding (lOFC→BLA) and subsequent use (BLA→lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

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“…To our knowledge, this is the first animal model demonstrating impaired behavioral responsiveness during focal limbic seizures, and relating impaired behavior to cortical neurophysiological changes (Sieu et al 2020; Sieu et al 2019; Sieu et al 2018). Genetic tools available in mice (such as optogenetics or genetically encoded calcium indicators) offer more possibilities to explore neuronal networks and mechanisms (Cardin et al 2010; Cardin 2012; Adamantidis et al 2015; Crouse et al 2020). Head-fixed mice provide good control of behavioral environment while allowing for simultaneous electrophysiologic recordings that would otherwise be difficult in a freely-moving animal.…”

Section: Discussionmentioning

confidence: 99%

A novel mouse model of focal limbic seizures that reproduces behavioral impairment associated with cortical slow wave activity

Sieu

Singla

Sharafeldin

et al. 2021

Preprint

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Patients with focal temporal lobe seizures often experience loss of consciousness. In humans, this loss of consciousness has been shown to be positively correlated with EEG neocortical slow waves, similar to those seen in non-REM sleep. Previous work in rat models of temporal lobe seizures suggests that decreased activity of subcortical arousal systems cause depressed cortical function during seizures. However, these studies were performed under light anesthesia, making it impossible to correlate behavior, and therefore consciousness, to electrophysiologic data. Further, the genetic and molecular toolkits allowing for precise study of the underlying neural circuitry are much more developed in mice than in rats. Here, we describe an awake-behaving, head-fixed mouse model of temporal lobe seizures with both spared and impaired behavior reflecting level of consciousness. Water-restricted mice were head-fixed on a running wheel and trained to associate an auditory stimulus to the delivery of a drop of water from a dispenser. To investigate the effect of seizures on behavior, seizures were electrically induced by stimulating either the left or right hippocampus via a chronically-implanted electrode, while mice were performing the task. Behavior was measured by monitoring lick responses to the auditory stimulus and running speed on the wheel. Further, local field potentials (LFP) signals were simultaneously recorded from hippocampus and orbitofrontal cortex (OFC). Induced focal seizures were 5-30s in duration, and repeatable for several weeks (n=20 animals). Behavioral responses showed a decrease in lick rate to auditory stimulus, and decreased running speed during seizures (p<0.01, n=20 animals). Interestingly, licking response to sound could vary from being impaired to normal during seizures. We found that behavioral impairment is correlated with large amplitude cortical slow-wave activity in frontal cortex, as seen in patients with temporal lobe seizures. These results suggest that induced focal limbic seizures in the mouse can impair consciousness and that the impaired consciousness is correlated with depressed cortical function resembling slow wave sleep. This novel mouse model has similar characteristics with previously studied rat models and human temporal lobe seizures. By leveraging the genetic and molecular techniques available in the mouse, this model can be used to further uncover fundamental mechanisms for loss of consciousness in focal seizures.

show abstract

Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances the learning of cue-reward contingency

Cited by 78 publications

References 64 publications

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

A novel mouse model of focal limbic seizures that reproduces behavioral impairment associated with cortical slow wave activity

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