Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning
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Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning. / Hervig, Mona E; Piilgaard, Louise; Božič, Tadej; Alsiö, Johan; Robbins, Trevor W.
In: Psychology and Neuroscience, Vol. 13, No. 3, 13.09.2020, p. 438-458.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning
AU - Hervig, Mona E
AU - Piilgaard, Louise
AU - Božič, Tadej
AU - Alsiö, Johan
AU - Robbins, Trevor W
N1 - © 2020 The Author(s).
PY - 2020/9/13
Y1 - 2020/9/13
N2 - Adapting behavior to a dynamic environment requires both steadiness when the environment is stable and behavioral flexibility in response to changes. Much evidence suggests that cognitive flexibility, which can be operationalized in reversal learning tasks, is mediated by cortico-striatal circuitries, with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, and we have previously reported differential roles of lateral (lOFC) and medial (mOFC) regions in a touchscreen serial visual reversal learning task for rats using pharmacological inactivation. Here, we investigated the effects of pharmacological overactivation of these regions using a glutamate transporter 1 (GLT-1) inhibitor, dihydrokainate (DHK), which increases extracellular glutamate by blocking its reuptake. We also tested the impact of antagonism of the serotonin 2A receptor (5-HT2AR), which modulates glutamate action, in the mOFC and lOFC on the same task. Overactivation induced by DHK produced dissociable effects in the mOFC and lOFC, with more prominent effects in the mOFC, specifically improving performance in the early, perseveration phase. Intra-lOFC DHK increased the number of omitted responses without affecting errors. In contrast, blocking the 5-HT2AR in the lOFC impaired reversal learning overall, while mOFC 5-HT2AR blockade had no effect. These results further support dissociable roles of the rodent mOFC and lOFC in deterministic visual reversal learning and indicate that modulating glutamate transmission through blocking the GLT-1 and the 5-HT2AR have different roles in these two structures.
AB - Adapting behavior to a dynamic environment requires both steadiness when the environment is stable and behavioral flexibility in response to changes. Much evidence suggests that cognitive flexibility, which can be operationalized in reversal learning tasks, is mediated by cortico-striatal circuitries, with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, and we have previously reported differential roles of lateral (lOFC) and medial (mOFC) regions in a touchscreen serial visual reversal learning task for rats using pharmacological inactivation. Here, we investigated the effects of pharmacological overactivation of these regions using a glutamate transporter 1 (GLT-1) inhibitor, dihydrokainate (DHK), which increases extracellular glutamate by blocking its reuptake. We also tested the impact of antagonism of the serotonin 2A receptor (5-HT2AR), which modulates glutamate action, in the mOFC and lOFC on the same task. Overactivation induced by DHK produced dissociable effects in the mOFC and lOFC, with more prominent effects in the mOFC, specifically improving performance in the early, perseveration phase. Intra-lOFC DHK increased the number of omitted responses without affecting errors. In contrast, blocking the 5-HT2AR in the lOFC impaired reversal learning overall, while mOFC 5-HT2AR blockade had no effect. These results further support dissociable roles of the rodent mOFC and lOFC in deterministic visual reversal learning and indicate that modulating glutamate transmission through blocking the GLT-1 and the 5-HT2AR have different roles in these two structures.
U2 - 10.1037/pne0000221
DO - 10.1037/pne0000221
M3 - Journal article
C2 - 33613854
VL - 13
SP - 438
EP - 458
JO - Psychology and Neuroscience
JF - Psychology and Neuroscience
SN - 1984-3054
IS - 3
ER -
ID: 258767292