T13. D-Cycloserine Facilitates Fear Extinction in Adolescent Rats and Differentially Affects Medial and Lateral Prefrontal Cortex Activation

2018 ◽  
Vol 83 (9) ◽  
pp. S133-S134
Author(s):  
Kathryn Baker ◽  
Gavan McNally ◽  
Rick Richardson
Author(s):  
Julio D. Vega-Torres ◽  
Matine Azadian ◽  
Raul Rios-Orsini ◽  
Arsenio L. Reyes-Rivera ◽  
Perla Ontiveros-Angel ◽  
...  

ABSTRACTBackgroundEmerging evidence demonstrates that diet-induced obesity disrupts corticolimbic circuits underlying emotional regulation. Studies directed at understanding how obesity alters brain and behavior are easily confounded by a myriad of complications related to obesity. This study investigated the early neurobiological stress response triggered by an obesogenic diet. Furthermore, this study directly determined the combined impact of a short-term obesogenic diet and adolescence on critical behavioral and molecular substrates implicated in emotion regulation and stress.MethodsAdolescent (postnatal day 31) or adult (postnatal day 81) Lewis rats were fed for one week with an experimental Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). We used the acoustic fear-potentiated startle (FPS) paradigm to determine the effects of the WD on cued fear conditioning and fear extinction. We used c-Fos mapping to determine the functional influence of the diet and stress on corticolimbic circuits.ResultsWe report that one-week WD consumption was sufficient to induce fear extinction deficits in adolescent rats, but not in adult rats. We identify fear-induced alterations in corticolimbic neuronal activation and demonstrate increased prefrontal cortex CRHR1 mRNA levels in the rats that consumed the WD.ConclusionsOur findings demonstrate that short-term consumption of an obesogenic diet during adolescence heightens behavioral and molecular vulnerabilities associated with risk for anxiety and stress-related disorders. Given that fear extinction promotes resilience, and that fear extinction principles are the foundation of psychological treatments for PTSD, understanding how obesogenic environments interact with the adolescent period to affect the acquisition and expression of fear extinction memories is of tremendous clinical relevance.HIGHLIGHTSShort-term WD consumption during adolescence impairs cued fear extinction memory retention in a fear-potentiated startle paradigm.Short-term WD consumption during adolescence attenuates neuronal activation to electric footshock stress in the basomedial nuclei of the amygdala.Short-term WD consumption increases CRHR1 mRNA levels in the medial prefrontal cortex.Adult LEW rats exhibit increased basal HPA axis tone and heightened emotional reactivity to footshock stress relative to adolescent rats.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander A. Aabedi ◽  
Sofia Kakaizada ◽  
Jacob S. Young ◽  
Jasleen Kaur ◽  
Olivia Wiese ◽  
...  

AbstractLexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.


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