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1.
eNeuro ; 11(3)2024 Mar.
Article in English | MEDLINE | ID: mdl-38471779

ABSTRACT

Self-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. The lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of the caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intrastriatal CNQX microinfusions, we demonstrate that the caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either the caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited greater impairment. We demonstrated that continuous perseverative errors in variable array were caused by putamen infusions, likely due to interference with the putamen's established role in monitoring motor feedback. Caudate infusions, however, did not affect continuous errors, but did cause an upward trend in recurrent perseveration, possibly reflecting interference with the caudate's established role in spatial working memory and goal-directed planning. In contrast to variable array performance, while both caudate and putamen infusions impaired fixed array responding, the combined effects were not additive, suggesting possible competing roles. Infusions into either region individually, but not simultaneously, led to continuous perseveration. Recurrent perseveration in fixed arrays was caused by putamen, but not caudate, infusions. These results are consistent overall with a role of caudate in planning and flexible responding and the putamen in more rigid habitual or automatic responding.


Subject(s)
Callithrix , Putamen , Animals , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Corpus Striatum , Caudate Nucleus/physiology
2.
J Neuroendocrinol ; 32(9): e12897, 2020 09.
Article in English | MEDLINE | ID: mdl-32935383

ABSTRACT

In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the long-term effects of suppressing adolescent gonadal hormone levels in a group of female Lister-hooded rats via administration of a gonadotrophin-releasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antide-treated female rats would exhibit more male-like behaviour than control females in novel environments (elevated-plus maze, open field and light-dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic-pituitary-gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide-treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide-treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c-Fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long-term effects on anxiety-related responses in female rats.


Subject(s)
Amygdala/drug effects , Anxiety , Behavior, Animal/drug effects , Oligopeptides/pharmacology , Ovary/drug effects , Amygdala/metabolism , Animals , Anxiety/metabolism , Anxiety/pathology , Down-Regulation/drug effects , Female , Gonadal Hormones/blood , Gonadal Hormones/metabolism , Hormone Antagonists/pharmacology , Male , Ovary/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats , Sex Characteristics , Sexual Maturation/drug effects , Sexual Maturation/physiology
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