Activity patterns of serotonin neurons underlying cognitive flexibility

Matias, Sara; Lottem, Eran; Dugué, Guillaume P.; Mainen, Zachary F.

doi:10.7554/elife.20552

Cited by 213 publications

(269 citation statements)

References 81 publications

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“…However, CBF cue responses extinguished more slowly compared to VTA DA during serial value or valence reversals. This difference may highlight a selective role for ACh in extinction learning, consistent with increased perseverative responding following manipulations of CBF activity and analogous to the serotonergic system (41)(42)(43). 25 Remarkably, we found that fluctuations in CBF and VTA DA activity as well as ACh release within the BLA were correlated.…”

supporting

confidence: 58%

Basal forebrain-derived acetylcholine encodes valence-free reinforcement prediction error

Sturgill

Hegedűs

et al. 2020

Preprint

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Acetylcholine (Ach) is released by the cholinergic basal forebrain (CBF) throughout the cortical mantle and is implicated in behavioral functions ranging from arousal to attention to learning. Yet what signal ACh provides to cortex remains unresolved, hindering our understanding of its functional roles. Here we demonstrate that the CBF signals unsigned reinforcement prediction error, in contrast to dopamine (DA) neurons that encode reward 25 prediction error. We show that both CBF neuronal activity and acetylcholine (ACh) release at cortical targets signal reinforcement delivery, acquire responses to predictive stimuli and show diminished responses to expected outcomes, hallmarks of a prediction error. To compare ACh with DA, we simultaneously monitored the activity of both neuromodulators during a serial reversal learning task. ACh tracked learning as swiftly as DA during acquisition but lagged 30 slightly during extinction, suggesting that these neuromodulators play complementary roles in reinforcement as their patterns of innervation, cellular targets, and signaling mechanisms are themselves complementary. Through retrograde viral tracing we show that the cholinergic and dopaminergic systems engage overlapping upstream circuits, accounting for their coordination during learning. This predictive and valence-free signal explains how ACh can proactively and 35 retroactively improve the processing of behaviorally important stimuli, be they good or bad.

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supporting

confidence: 58%

Basal forebrain-derived acetylcholine encodes valence-free reinforcement prediction error

Sturgill

Hegedűs

et al. 2020

Preprint

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“…Interestingly, we found prominent labeling in regions implicated in regulating the arousal and the affective state of the animal, including the basolateral amygdala, CA1 region of the ventral hippocampus, paraventricular (PVT), and reuneins (RE) nuclei of the thalamus, lateral supramammillary nucleus (SUMl), and serotonergic and cholinergic inputs from the dorsal raphe and basal forebrain, respectively (Hu, 2016;Reppucci & Petrovich, 2016;Swanson, 2000;Vertes, Linley, & Hoover, 2015). Many of these regions have been shown to modulate their activity in response to rewarding or aversive stimuli or to cues that predict such outcomes (Beyeler et al, 2018;Burgos-Robles et al, 2017;Hangya, Ranade, Lorenc, & Kepecs, 2015;Jimenez et al, 2018;Matias, Lottem, Dugué, & Mainen, 2017;Zhu, Wienecke, Nachtrab, & Chen, 2016). The CLA may therefore integrate some of these response features and broadcast its output to the cortex to modulate processing under emotionally salient conditions.…”

Section: Discussionmentioning

confidence: 99%

Input–output organization of the mouse claustrum

Zingg

Dong

Tao

et al. 2018

J of Comparative Neurology

177

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Progress in determining the precise organization and function of the claustrum has been hindered by the difficulty in reliably targeting these neurons. To overcome this, we used a projection-based targeting strategy to selectively label claustrum principal neurons. Combined with adeno-associated virus (AAV) and monosynaptic rabies tracing techniques, we systematically examined the pre-synaptic input and axonal output of this structure. We found that claustrum neurons projecting to retrosplenial cortex (RSP) collateralize extensively to innervate a variety of higher-order cortical regions. No subcortical labeling was found, with the exception of sparse terminals in the basolateral amygdala (BLA). This pattern of output was similar to cingulate- and visual cortex-projecting claustrum neurons, suggesting a common targeting scheme among these projection-defined populations. Rabies virus tracing directly demonstrated widespread synaptic inputs to RSP-projecting claustrum neurons from both cortical and subcortical areas. The strongest inputs arose from classically defined limbic regions, including medial prefrontal cortex, anterior cingulate, basolateral amygdala, ventral hippocampus, and neuromodulatory systems such as the dorsal raphe and cholinergic basal forebrain. These results suggest that the claustrum may integrate information related to the emotional salience of stimuli and may globally modulate cortical state by broadcasting its output uniformly across a variety of higher cognitive centers.

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“…Activation of serotonin also causes sustained effects. During a reversal learning task, serotonin neurons were activated when the association pattern of cue and reward was altered . Indeed, the activation of serotonin promoted reversal learning, suggesting that serotonin enhances flexibility in learning.…”

Section: Sustained Dopamine and Serotonin Effects On Behaviormentioning

confidence: 99%

“…During a reversal learning task, serotonin neurons were activated when the association pattern of cue and reward was altered . Indeed, the activation of serotonin promoted reversal learning, suggesting that serotonin enhances flexibility in learning. In a social conditioning task, where mice showed a preference for a context where they were exposed to home cage mates, blockade of 5‐HT 1B receptor in the NAc during conditioning eliminated social preference in assessments 2 days after the conditioning .…”

Section: Sustained Dopamine and Serotonin Effects On Behaviormentioning

confidence: 99%

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Yagishita

2019

Psychiatry Clin Neurosci

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Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.

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Activity patterns of serotonin neurons underlying cognitive flexibility

Cited by 213 publications

References 81 publications

Basal forebrain-derived acetylcholine encodes valence-free reinforcement prediction error

Basal forebrain-derived acetylcholine encodes valence-free reinforcement prediction error

Input–output organization of the mouse claustrum

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

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