Medial Prefrontal Cortex Serotonin Input Regulates Cognitive Flexibility in Mice

Morgan, Ashlea A.; Alves, Nuno Dinis; Stevens, Gregory S.; Yeasmin, Tamanna T; MacKay, Alexandra S.; Power, Saige K; Sargin, Derya; Hanna, Carla; Adib, Arwa L; Ziolkowski-Blake, Annette; Lambe, Evelyn K.; Ansorge, Mark S.

doi:10.1101/2023.03.30.534775

Cited by 5 publications

(2 citation statements)

References 95 publications

(134 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, optogenetic stimulation of DRN 5-HT neurons 170,171 or their projections to OFC and a region of rodent medial PFC thought to be homologous to ACC 172 promotes waiting for rewards 173 , whereas chemical inhibition of DRN 5-HT neurons 174 or blockade of 5-HT 1A receptors 175 reduces waiting for rewards. Thirdly, the 5-HT system is theorized to regulate learning and cognitive flexibility 28,150,[176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192] . Integrated value signals could indicate that time and resources are available for safe and fruitful learning 10,28,176,183,190,193 , by promoting exploration and information-seeking through DRN projections to ACC and ventrolateral PFC 99,194,195 or by accelerating the rate of learning through 5-HT-mediated neuroplasticity across the brain 196 .…”

Section: Discussionmentioning

confidence: 99%

Dorsal raphe neurons signal integrated value during multi-attribute decision-making

Feng,

Bromberg-Martin,

Monosov

2023

Preprint

View full text Add to dashboard Cite

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when grappling with reward uncertainty. However, whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider all these attributes to make a choice, is unclear. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes. Remarkably, these neurons commonly integrated offer attributes in a manner that reflected monkeys’ overall preferences for amount, delay, and uncertainty. After decision-making, in response to post-decision feedback, these same neurons signaled signed reward prediction errors, suggesting a broader role in tracking value across task epochs and behavioral contexts. Our data illustrate how DRN participates in integrated value computations, guiding theories of DRN in decision-making and psychiatric disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Dorsal raphe neurons signal integrated value during multi-attribute decision-making

Feng,

Bromberg-Martin,

Monosov

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The evolutionary forces that have shaped it likely predate the Permian-Triassic bottleneck 252 million years ago; the overarching functionality of the serotonergic matrix appears to be associated with neuroplasticity. [11][12][13] The serotonergic matrix may maintain a dynamic balance between synaptic pliability and stability (metaphorically, keeping brain networks near the "melting temperature"). In particular, it is known to support transitions among global brain states such as wakefulness and sleep.…”

Section: Introductionmentioning

confidence: 99%

Qualitative Observations of Transgenically Individualized Serotonergic Fibers in the Mouse Telencephalon

Haiman,

Mays,

Roostaeyan

et al. 2023

Preprint

View full text Add to dashboard Cite

The matrix of serotonergic axons (fibers) is a constant feature of neural tissue in vertebrate brains. Its fundamental role appears to be associated with the spatiotemporal control of neuroplasticity. The densities of serotonergic fibers vary across brain regions, but their development and maintenance remain poorly understood. A specific fiber concentration is achieved as the result of the dynamics of a large number of individual fibers, each of which can make trajectory decisions independently of other fibers. Bridging these processes, operating on very different spatial scales, remains a challenge in neuroscience. The study provides the first qualitative description of individually-tagged serotonergic axons in four selected telencephalic regions (cortical and subcortical) of the mouse brain. Based on our previous implementation of the Brainbow toolbox in this system, serotonergic fibers were labeled with random intensity combinations of three fluorophores and imaged with high-resolution confocal microscopy. All examined regions contained serotonergic fibers of diverse identities and morphologies, often traveling in close proximity to one another. Some fibers transitioned among several morphologies in the same imaged volume. High fiber densities appeared to be associated with highly tortuous fiber segments produced by some individual fibers. This study supports efforts to predictively model the self-organization of the serotonergic matrix in all vertebrates, including regenerative processes in the adult human brain.

show abstract

The role of the GABAergic cells of the median raphe region in reinforcement-based learning

Chaves,

Török,

Fazekas

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Learning and memory are important in everyday life as well as in pathological conditions. The median raphe region (MRR) contributes to memory formation; however, its precise role and the neurotransmitters involved have yet to be elucidated. To address this issue, we stimulated the MRR neurons of mice by chemogenetic technique and studied them in the operant conditioning and active avoidance tests. The virus carrier infected a variety of neuron types including both GABAergic and glutamatergic ones. Behavior was not influenced by stimulation. We hypothesize that the lack of effect was due to opposing effects exerted via GABAergic and glutamatergic neurons. Therefore, next we used VGAT-Cre mice that allowed the specific manipulation of MRR-GABAergic neurons. The stimulation did not affect behavior in the learning phase of the operant conditioning task, but increased reward preference and total responses when operant contingencies were reversed. The enhanced responsiveness might be a proclivity to impulsive behavior. Stimulation facilitated learning in the active avoidance test but did not affect reversal learning in this paradigm. Our findings suggest that MRR-GABAergic neurons are involved in both learning and reversal learning, but the type of learning that is affected depends on the task.

show abstract

Medial Prefrontal Cortex Serotonin Input Regulates Cognitive Flexibility in Mice

Cited by 5 publications

References 95 publications

Dorsal raphe neurons signal integrated value during multi-attribute decision-making

Dorsal raphe neurons signal integrated value during multi-attribute decision-making

Qualitative Observations of Transgenically Individualized Serotonergic Fibers in the Mouse Telencephalon

The role of the GABAergic cells of the median raphe region in reinforcement-based learning

Contact Info

Product

Resources

About