scholarly journals Exposure to the Synthetic Progestin, 17α-Hydroxyprogesterone Caproate During Development Impairs Cognitive Flexibility in Adulthood

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Jari Willing ◽  
Christine K. Wagner
Keyword(s):  
Prefrontal Cortex ◽  
Progesterone Receptor ◽  
Medial Prefrontal Cortex ◽  
Cognitive Flexibility ◽  
Neural Circuit ◽  
Developing Brain ◽  
Premature Delivery ◽  
Cognitive Behaviors ◽  
Hydroxyprogesterone Caproate ◽  
Cell Layers

Abstract The synthetic progestin, 17α-hydroxyprogesterone caproate, is increasingly used for the prevention of premature birth in at-risk women, despite little understanding of the potential effects on the developing brain. Rodent models suggest that many regions of the developing brain are sensitive to progestins, including the mesocortical dopamine pathway, a neural circuit important for complex cognitive behaviors later in life. Nuclear progesterone receptor is expressed during perinatal development in dopaminergic cells of the ventral tegmental area that project to the medial prefrontal cortex. Progesterone receptor is also expressed in the subplate and in pyramidal cell layers II/III of medial prefrontal cortex during periods of dopaminergic synaptogenesis. In the present study, exposure to 17α-hydroxyprogesterone caproate during development of the mesocortical dopamine pathway in rats altered dopaminergic innervation of the prelimbic prefrontal cortex and impaired cognitive flexibility with increased perseveration later in life, perhaps to a greater extent in males. These studies provide evidence for developmental neurobehavioral effects of a drug in widespread clinical use and highlight the need for a reevaluation of the benefits and potential outcomes of prophylactic progestin administration for the prevention of premature delivery.

scholarly journals Expecting social punishment facilitates control over a decision under uncertainty by recruiting medial prefrontal cortex

2019 ◽  
Author(s):  
Jaejoong Kim ◽  
Bumseok Jeong
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Computational Models ◽  
Neural Circuit ◽  
Computational Modelling ◽  
Causal Modeling ◽  
Optimal Decision ◽  
Stressful Situation ◽  
Decision Under Uncertainty ◽  
Incorrect Choice

AbstractIn many decision-making situations, uncertainty facilitates suboptimal choices. However, when individuals are in a socially dangerous situation such that wrong choice would lead to a social punishment such as blame of the supervisor, they might try to minimize suboptimal choices to avoid it. In this functional MRI study, 46 participants performed a choice task in which the probability of a correct choice with a given cue and the conditional probability of blame feedback (by making an incorrect choice) changed continuously. Using computational models of behavior, we found that participants optimized their decision by suppressing the decision noise induced by uncertainty. Simultaneously, expecting blame significantly deteriorated participants’ mood. Model-based fMRI analyses and dynamic causal modeling revealed that the optimization mechanism based on the expectation of being blamed was controlled by a neural circuit centered on right medial prefrontal cortex. These results show novel behavioral and neural mechanisms regarding how humans optimize uncertain decisions under the expectation of being blamed that negatively influences mood.Significance StatementPeople occasionally encounter a situation that forces us to make an optimal decision under uncertainty, which is difficult, and a failure to make a good choice might be blamed by their supervisor. Although it might be hard to make right decision, they make more effort to make a good decision, which might help them to escape from the aversive outcome. However, such kind of stressful situation influences our mood to be negative. Using the computational modelling, we showed that participants computed how it is likely to be blamed and this computation motivated people to control uncertainty-induced decision noise by recruiting a neural circuit centered on the medial prefrontal cortex. However, an expectation of being blamed significantly deteriorated participants’ mood.

scholarly journals Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

2021 ◽  
Author(s):  
TSUYOSHI HATTORI ◽  
Stanislav M Cherepanov ◽  
Ryo Sakaga ◽  
Jureepon Roboon ◽  
Dinh Thi Nguyen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Medial Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Social Memory ◽  
Behavioral Abnormalities ◽  
Survival And Reproduction

Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

scholarly journals Putting objects in context: A prefrontal–hippocampal–perirhinal cortex network

2020 ◽  
Vol 4 ◽  
pp. 239821282093762
Author(s):  
G. R. I. Barker ◽  
E. C. Warburton
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Test Performance ◽  
Neural Circuit ◽  
Perirhinal Cortex ◽  
Impaired Performance ◽  
Cortex Lesion ◽  
Object Recognition Memory ◽  
And Performance ◽  
Bilateral Lesions

When we encounter an object, we spontaneously form associations between the object and the environment in which it was encountered. These associations can take a number of different forms, which include location and context. A neural circuit between the hippocampus, medial prefrontal cortex and perirhinal cortex is critical for object-location and object-sequence associations; however, how this neural circuit contributes to the formation of object-context associations has not been established. Bilateral lesions were made in the hippocampus, medial prefrontal cortex or perirhinal cortex to examine each region contribution to object-context memory formation. Next, a disconnection lesion approach was used to examine the necessity of functional interactions between the hippocampus and medial prefrontal cortex or perirhinal cortex. Spontaneous tests of preferential exploration were used to assess memory for different types of object-context associations. Bilateral lesion in the hippocampus, medial prefrontal cortex or perirhinal cortex impaired performance in both an object-place-context and an object-context task. Disconnection of the hippocampus from either the medial prefrontal cortex or perirhinal cortex impaired performance in both the object-place-context and object-context task. Interestingly, when object recognition memory was tested with a context switch between encoding and test, performance in the hippocampal and medial prefrontal cortex lesion groups was disrupted and performance in each disconnection group (i.e. hippocampus + medial prefrontal cortex, hippocampus + perirhinal cortex) was significantly impaired. Overall, these experiments establish the importance of the hippocampal-medial prefrontal-perirhinal cortex circuit for the formation of object-context associations.

Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex

2015 ◽  
Vol 125 ◽  
pp. 73-79 ◽  
Author(s):  
Erica R. Glasper ◽  
Elizabeth A. LaMarca ◽  
Miriam E. Bocarsly ◽  
Maria Fasolino ◽  
Maya Opendak ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Cognitive Flexibility ◽  
Dendritic Spine ◽  
Sexual Experience ◽  
Spine Density ◽  
Dendritic Spine Density
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