TY - JOUR
T1 - Functional Heterogeneity within the Primate Ventral Striatum for Motivational Regulation
AU - Iwaoki, Haruhiko
AU - Hori, Yukiko
AU - Hori, Yuki
AU - Mimura, Koki
AU - Oyama, Kei
AU - Nagai, Yuji
AU - Hirabayashi, Toshiyuki
AU - Ken-Ichi, Inoue
AU - Takada, Masahiko
AU - Higuchi, Makoto
AU - Minamimoto, Takafumi
N1 - Publisher Copyright:
Copyright © 2025 Iwaoki et al.
PY - 2025/5/21
Y1 - 2025/5/21
N2 - The ventral striatum (VS) is a key brain region for reward processing and motivation, and its dysfunctions have been implicated in psychiatric disorders such as apathy and obsessive–compulsive disorder. Although functional heterogeneity within the VS has been well established in rodents, its relevance and mechanisms in primates remain unclear. To address this issue, we performed bilateral pharmacological inactivation of the VS in two male macaque monkeys using muscimol, a GABAA receptor agonist. Precise targeting was achieved through computed tomography and magnetic resonance imaging. Behavioral effects were evaluated using two methods: a goal-directed task with variable rewards and analysis of spontaneous behavior. Our results demonstrated that anterior (a)VS inactivation induced a hypoactivity state that we termed “resting,” whereas posterior (p)VS inactivation elicited compulsive-like “checking” behaviors. Notably, neither the aVS nor the pVS inactivation affected reward value or drive processing, thus differentiating aVS and pVS from those involved in incentive motivation, such as the rostromedial caudate and ventral pallidum. Retrograde tracing demonstrated distinct anatomical projection patterns for the aVS and pVS, supporting their functional segregation. Together, the present results suggest the functional heterogeneity of the primate VS along its anterior–posterior axis, with the aVS and pVS participating in distinct motivational control circuits. Our findings may have important implications for understanding the neural mechanisms of psychiatric disorders and for the development of new therapeutic approaches.
AB - The ventral striatum (VS) is a key brain region for reward processing and motivation, and its dysfunctions have been implicated in psychiatric disorders such as apathy and obsessive–compulsive disorder. Although functional heterogeneity within the VS has been well established in rodents, its relevance and mechanisms in primates remain unclear. To address this issue, we performed bilateral pharmacological inactivation of the VS in two male macaque monkeys using muscimol, a GABAA receptor agonist. Precise targeting was achieved through computed tomography and magnetic resonance imaging. Behavioral effects were evaluated using two methods: a goal-directed task with variable rewards and analysis of spontaneous behavior. Our results demonstrated that anterior (a)VS inactivation induced a hypoactivity state that we termed “resting,” whereas posterior (p)VS inactivation elicited compulsive-like “checking” behaviors. Notably, neither the aVS nor the pVS inactivation affected reward value or drive processing, thus differentiating aVS and pVS from those involved in incentive motivation, such as the rostromedial caudate and ventral pallidum. Retrograde tracing demonstrated distinct anatomical projection patterns for the aVS and pVS, supporting their functional segregation. Together, the present results suggest the functional heterogeneity of the primate VS along its anterior–posterior axis, with the aVS and pVS participating in distinct motivational control circuits. Our findings may have important implications for understanding the neural mechanisms of psychiatric disorders and for the development of new therapeutic approaches.
KW - checking
KW - monkey
KW - motivation
KW - muscimol
KW - resting
KW - ventral striatum
UR - https://www.scopus.com/pages/publications/105005654162
UR - https://www.scopus.com/pages/publications/105005654162#tab=citedBy
U2 - 10.1523/JNEUROSCI.2430-24.2025
DO - 10.1523/JNEUROSCI.2430-24.2025
M3 - Article
C2 - 40228898
AN - SCOPUS:105005654162
SN - 0270-6474
VL - 45
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 21
M1 - e2430242025
ER -