A molecularly integrated amygdalo-fronto-striatal network coordinates flexible learning and memory

Li, Dan C.; Dighe, Niharika M.; Barbee, Britton R.; Pitts, Elizabeth G.; Kochoian, Brik; Blumenthal, Sarah A.; Figueroa, Janet; Leong, Traci; Gourley, Shannon L.

doi:10.1038/s41593-022-01148-9

Cited by 19 publications

(20 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, vHC-to-MO projections appear necessary to update outcome value information for future choice. The vHC also innervates the adjacent, ventrolateral orbitofrontal cortex, but notably, we found no effects if we chemogenetically inactivated neurons in this region using identical procedures ( Figure S5 ), supporting the notion that these subregions are functionally distinct, and that the ventrolateral region may be particularly attuned to reward contingency or scenarios in which value and contingency information must be integrated ( Parkes et al, 2017 ; Li et al, 2022 ).…”

Section: Resultssupporting

confidence: 62%

Medial orbitofrontal neurotrophin systems integrate hippocampal input into outcome-specific value representations

et al. 2022

Self Cite

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 62%

Medial orbitofrontal neurotrophin systems integrate hippocampal input into outcome-specific value representations

et al. 2022

Self Cite

View full text Add to dashboard Cite

“…Our findings show that loss of α2δ-1-signalling disrupts this adaptive step. We used the PR test to measure effort exertion, because it avoids the confound of having to select between different options, such as choosing between two actions with different probability of reward or two different locations with different rewards 20,38,40,68,93,94 . In fact, PR test is a standard test to measure effort exertion both in rodents and humans 37,[84][85][86] .…”

Section: Discussionmentioning

confidence: 99%

“…For example, learning induces the formation of new spines in the Orbitofrontal cortex (OFC) neurons projecting to the DMS. These newly formed spines are necessary to retrieve previous memories of learned actions and select actions with higher reward 20 . It is possible that OFC and ACC connections to the DMS have synergistic functions to control adaptation of goal-directed learned behaviors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control

Fpu¹,

Lawal

Sakers

et al. 2021

Preprint

View full text Add to dashboard Cite

Synaptogenesis is essential for circuit development; however, whether it is critical in adulthood for learning and performance of voluntary behaviors is unknown. Here we show that reward-based training in mice induces excitatory synapse formation onto Anterior Cingulate Cortex (ACC) neurons projecting to the dorsomedial striatum (DMS). We used germline and conditional knockout mice for Gabapentin/Thrombospondin receptor α2δ-1, which is required for excitatory synaptogenesis in the cortex, and found that loss of α2δ-1 in the adult ACC-DMS circuit is sufficient to abolish training-induced excitatory synaptogenesis. Surprisingly, this manipulation did not affect learning, instead caused a profound increase in effort exertion. Optogenetic activation of ACC-DMS neurons was sufficient to diminish effort exertion in wildtype mice and rescued the effort/reward evaluation deficit of the conditional α2δ-1 mutants. These results highlight the importance of synaptogenic signaling in the adult and pinpoint the ACC-DMS neuronal circuit as the controller of effort exertion during voluntary behaviors.

show abstract

“…Prior work reveals that the DMS supports flexible, goal-directed conditioned responding. Reducing the activity of the DMS through lesion or pharmacological inhibition impairs flexible responding in a variety of tasks [47,16,48,19,49]. To be interpreted in this conceptual framework, the present results suggest that CB1R signaling promotes DMS activation and that inhibiting CB1Rs signaling decreases DMS output to impair Pavlovian devaluation sensitivity.…”

Section: Discussionmentioning

confidence: 64%

Dorsomedial Striatum CB1R signaling is required for Pavlovian outcome devaluation in male Long Evans rats and reduces inhibitory synaptic transmission in both sexes

Stapf,

Keefer,

McInerney

et al. 2024

Preprint

View full text Add to dashboard Cite

Cannabinoid-1 receptor (CB1R) signaling in the dorsal striatum regulates the shift from flexible to habitual behavior in instrumental outcome devaluation. Based on prior work establishing individual, sex, and experience-dependent differences in Pavlovian behaviors, we predicted a role for dorsomedial striatum CB1R signaling in driving sign-tracking and rigid responding in Pavlovian outcome devaluation. We trained male and female rats in Pavlovian Lever Autoshaping to determine sign-, or goal- or intermediate tracking groups. After extended Pavlovian training, we gave intra-DMS infusions of the CB1R inverse agonist, rimonabant, before satiety-induced outcome devaluation test sessions, in which we sated rats on training pellets (devalued) or home cage chow (valued) and examined responding to cues in brief nonreinforced Pavlovian Lever Autoshaping sessions. Overall, DMS CB1R signaling inhibition blocked Pavlovian outcome devaluation. After extended training, male rats were sensitive to devaluation while female rats were not. Inhibition of DMS CB1R signaling impaired Pavlovian outcome devaluation in male sign-tracking rats making their behavior more rigid but had no effects in female sign-tracking rats. Intra-DMS rimonabant infusions before reinforced sessions had no effects on Pavlovian sign- or goal-tracking in either sex. The sex-specific and CB1R-dependent effects were specific to outcome devaluation and were consistent between sign- and goal-tracking groups. Our results demonstrate that DMS endocannabinoid receptor signaling regulates behavioral flexibility in a sex-specific manner, suggesting differences in CB1R signaling in DMS between male and female rats.

show abstract

A molecularly integrated amygdalo-fronto-striatal network coordinates flexible learning and memory

Cited by 19 publications

References 72 publications

Medial orbitofrontal neurotrophin systems integrate hippocampal input into outcome-specific value representations

Medial orbitofrontal neurotrophin systems integrate hippocampal input into outcome-specific value representations

Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control

Dorsomedial Striatum CB1R signaling is required for Pavlovian outcome devaluation in male Long Evans rats and reduces inhibitory synaptic transmission in both sexes

Contact Info

Product

Resources

About