TY - JOUR
T1 - Serotonin regulates performance nonmonotonically in a spatial working memory network
AU - Cano-Colino, Maria
AU - Almeida, Rita
AU - Gomez-Cabrero, David
AU - Artigas, Francesc
AU - Compte, Albert
N1 - Generated from Scopus record by KAUST IRTS on 2021-02-16
PY - 2014/1/1
Y1 - 2014/1/1
N2 - The prefrontal cortex (PFC) contains a dense network of serotonergic [serotonin, 5-hydroxytryptamine (5-HT)] axons, and endogenous 5-HT markedly modulates PFC neuronal function via several postsynaptic receptors. The therapeutic action of atypical antipsychotic drugs, acting mainly via 5-HT receptors, also suggests a role for serotonergic neurotransmission in cognitive functions. However, psychopharmacological studies have failed to find a consistent relationship between serotonergic transmission and cognitive functions of the PFC, including spatial working memory (SWM). Here, we built a computational network model to investigate 5-HT modulation of SWM in the PFC. We found that 5-HT modulates network's SWM performance nonmonotonically via 5-HT1A and 5-HT2A receptors, following an inverted U-shape. This relationship may contribute to blur the effects of serotonergic agents in previous SWM group-based behavioral studies. Our simulations also showed that errors occurring at low and high 5-HT concentrations are due to different network dynamics instabilities, suggesting that these 2 conditions can be distinguished experimentally based on their distinct dependency on experimental variables. We inferred specific predictions regarding the expected behavioral effects of serotonergic agents in 2 classic working-memory tasks. Our results underscore the relevance of identifying different error types in SWM tasks in order to reveal the association between neuromodulatory systems and SWM. © The Author 2013. Published by Oxford University Press. All rights reserved.
AB - The prefrontal cortex (PFC) contains a dense network of serotonergic [serotonin, 5-hydroxytryptamine (5-HT)] axons, and endogenous 5-HT markedly modulates PFC neuronal function via several postsynaptic receptors. The therapeutic action of atypical antipsychotic drugs, acting mainly via 5-HT receptors, also suggests a role for serotonergic neurotransmission in cognitive functions. However, psychopharmacological studies have failed to find a consistent relationship between serotonergic transmission and cognitive functions of the PFC, including spatial working memory (SWM). Here, we built a computational network model to investigate 5-HT modulation of SWM in the PFC. We found that 5-HT modulates network's SWM performance nonmonotonically via 5-HT1A and 5-HT2A receptors, following an inverted U-shape. This relationship may contribute to blur the effects of serotonergic agents in previous SWM group-based behavioral studies. Our simulations also showed that errors occurring at low and high 5-HT concentrations are due to different network dynamics instabilities, suggesting that these 2 conditions can be distinguished experimentally based on their distinct dependency on experimental variables. We inferred specific predictions regarding the expected behavioral effects of serotonergic agents in 2 classic working-memory tasks. Our results underscore the relevance of identifying different error types in SWM tasks in order to reveal the association between neuromodulatory systems and SWM. © The Author 2013. Published by Oxford University Press. All rights reserved.
UR - https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bht096
UR - http://www.scopus.com/inward/record.url?scp=84885054976&partnerID=8YFLogxK
U2 - 10.1093/cercor/bht096
DO - 10.1093/cercor/bht096
M3 - Article
SN - 1460-2199
VL - 24
SP - 2449
EP - 2463
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 9
ER -