Neural substrates of habit

Malvaez, Melissa

doi:10.1002/jnr.24552

Cited by 18 publications

(22 citation statements)

References 136 publications

(172 reference statements)

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“…How does the MS downregulating DA population activity in SNc affect strategy switching? As rewarded behaviors are repeated over time, and learning progresses, motor action plans become stereotyped [36][37][38] . DA release that is initially seen in VS and is predictive of learning rate 8,9 , begins to dissipate 12 .…”

Section: Discussionmentioning

confidence: 99%

Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity

Bortz

Feistritzer

Power

et al. 2022

Preprint

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Strategy switching is a form of cognitive flexibility that requires inhibiting a previously successful strategy and then switching to a new strategy of a different categorical modality. It is dependent on dopamine (DA) receptor activation and release in ventral striatum and prefrontal cortex, two primary targets of ventral tegmental area (VTA) DA projections. Although the circuitry that underlies strategy switching early in learning has been studied, few studies have examined it after extended discrimination training. This may be important as DA activity and release patterns change across learning, with several studies demonstrating a critical role for substantia nigra pars compacta (SNc) DA activity and release once behaviors are well learned. Our previous studies demonstrated that medial septum (MS) activation simultaneously increased VTA and decreased SNc DA population activity, as well as improved reversal learning via these actions on DA population activity. We hypothesized that MS activation would improve strategy switching both early in learning and after extended training through its ability to increase VTA DA population activity and decrease SNc DA population activity, respectively. To test this, we activated the MS of male and female rats with designer receptors exclusively activated by designer drugs and measured their performance on an operant-based strategy switching task, following 1, 10, or 15 days of discrimination training. Contrary to our hypothesis, MS activation did not affect strategy switching after 1 day of discrimination training. MS activation improved strategy switching after 10 days of discrimination training, but only in females. MS activation improved strategy switching in both sexes after 15 days of discrimination training. This improvement in strategy switching was attenuated by intra-ventral subiculum bicuculline infusion, which selectively inhibited the MS-mediated decrease in SNc DA population activity, and prevented by infusion of both bicuculline and scopolamine, which inhibited both the MS-mediated decrease in SNc and increase in VTA DA population activity. These data indicate that MS activation improves strategy switching, but only once the original strategy has been sufficiently well learned. They also suggest that the mechanism by which this occurs is likely via the MS's regulation of DA neuron responsivity, primarily via its ability to down-regulate DA population activity in the SNc.

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Section: Discussionmentioning

confidence: 99%

Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity

Bortz

Feistritzer

Power

et al. 2022

Preprint

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“…Both the BLA and mOFC are needed for the sensitivity of instrumental choice to devaluation (Balleine et al, 2003;Ostlund and Balleine, 2008;Johnson et al, 2009;Bradfield et al, 2015Bradfield et al, , 2018Gourley et al, 2016). This function may, therefore, be achieved via alternate pathways, perhaps those to the striatum (Hoover and Vertes, 2011;Corbit et al, 2013;van Holstein et al, 2020), a region heavily implicated in action-outcome memory (Malvaez and Wassum, 2018;Malvaez et al, 2018b;Malvaez, 2020).…”

Section: Discussionmentioning

confidence: 99%

The Medial Orbitofrontal Cortex–Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice

et al. 2021

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Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC-BLA connections in reward-directed behavior. We found evidence that the mOFCfiBLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLAfimOFC pathway is not needed to use the identity of an expected reward to guide choice but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, the data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.

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“…Both the BLA and mOFC are needed for the sensitivity of instrumental choice to devaluation (Balleine et al, 2003; Ostlund and Balleine, 2008; Johnson et al, 2009; Bradfield et al, 2015; Gourley et al, 2016; Bradfield et al, 2018). This function may, therefore, be achieved via alternate pathways, perhaps those to the striatum (Hoover and Vertes, 2011; Corbit et al, 2013; van Holstein et al, 2020), a region heavily implicated in action-outcome memory (Malvaez et al, 2018b; Malvaez and Wassum, 2018; Malvaez, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Rats received two PIT tests, counterbalanced for order, one following intra-BLA infusion of CNO to inactivate hM4Di-expressing mOFC axons and terminals in the BLA and one following infusion of aCSF vehicle. We chose a vehicle-infused control to provide a within-subject comparison and based on evidence that CNO when infused at this dose into the BLA has no effect on the expression of PIT, similar reward-related behaviors, BLA activity, or OFC terminal activity in the BLA in the absence of the hM4Di transgene (Lichtenberg et al, 2017;Malvaez et al, 2019). During each test, both levers were continuously present, but lever pressing was not rewarded.…”

Section: The Mofcbla Pathway Regulates the Influence Of Stimulus-outcome Memories Over Decision Making And Adaptive Conditional Respondimentioning

confidence: 99%

“…Standard surgical procedures, described previously (Malvaez et al, 2015;Lichtenberg et al, 2017;Malvaez et al, 2019), were used for all surgeries. Rats were anesthetized with isoflurane (4-5% induction, 1-2% maintenance) and a nonsteroidal anti-inflammatory agent was administered pre-and post-operatively to minimize pain and discomfort, as well as post-operative antibiotics.…”

Section: Surgerymentioning

confidence: 99%

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The medial orbitofrontal cortex - basolateral amygdala circuit regulates the influence of reward cues on adaptive behavior and choice

Lichtenberg

Sepe-Forrest

Pennington

et al. 2021

Preprint

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Adaptive reward-related decision making requires accurate prospective consideration of the current availability and desirability of potential rewarding options. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome guided behavior, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC→BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental cues to predict which reward is available, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive cue responses. By contrast, the BLA→mOFC pathway is not needed to use cues to know which reward is available but is needed to use the current desirability of that reward to infer how advantageous it would be to respond to the cue. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, these data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.SIGNIFICANCE STATEMENTTo make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding events might be available and how desirable those events are currently. Such prospective considerations are critical for adaptive decision making but are disrupted in many psychiatric diseases. Here we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.

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Neural substrates of habit

Cited by 18 publications

References 136 publications

Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity

Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity

The Medial Orbitofrontal Cortex–Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice

The medial orbitofrontal cortex - basolateral amygdala circuit regulates the influence of reward cues on adaptive behavior and choice

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