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1. TrkB Activation during a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus

   https://doi.org/10.1523/JNEUROSCI.2598-18.2019  

   Mudd, David B.; Balmer, Timothy S.; Kim, So Yeon; Machhour, Noura; Pallas, Sarah L. (June 2019, The Journal of Neuroscience)

   na (Ed.)

   During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al., 2005, 2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In V1, BDNF and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999; Huang et al., 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33–P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC. 

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2. Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes

   https://doi.org/10.1177/24705470211029254  

   Woo, Elizabeth; Sansing, Lauren H.; Arnsten, Amy F.; Datta, Dibyadeep (January 2021, Chronic Stress)

   Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC), a recently evolved brain region that provides top-down regulation of thought, action, and emotion. PFC neurons generate top-down goals through recurrent excitatory connections on spines. This persistent firing is the foundation for higher cognition, including working memory, and abstract thought. However, exposure to acute uncontrollable stress drives high levels of catecholamine release in the PFC, which activates feedforward calcium-cAMP signaling pathways to open nearby potassium channels, rapidly weakening synaptic connectivity to reduce persistent firing. Chronic stress exposures can further exacerbate these signaling events leading to loss of spines and resulting in marked cognitive impairment. In this review, we discuss how stress signaling mechanisms can lead to spine loss, including changes to BDNF-mTORC1 signaling, calcium homeostasis, actin dynamics, and mitochondrial actions that engage glial removal of spines through inflammatory signaling. Stress signaling events may be amplified in PFC spines due to cAMP magnification of internal calcium release. As PFC dendritic spine loss is a feature of many cognitive disorders, understanding how stress affects the structure and function of the PFC will help to inform strategies for treatment and prevention. 

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3. A multicohort geometric deep learning study of age dependent cortical and subcortical morphologic interactions for fluid intelligence prediction

   https://doi.org/10.1038/s41598-022-22313-x  

   Wu, Yunan; Besson, Pierre; Azcona, Emanuel A.; Bandt, S. Kathleen; Parrish, Todd B.; Breiter, Hans C.; Katsaggelos, Aggelos K. (December 2022, Scientific Reports)

   Abstract The relationship of human brain structure to cognitive function is complex, and how this relationship differs between childhood and adulthood is poorly understood. One strong hypothesis suggests the cognitive function of Fluid Intelligence (Gf) is dependent on prefrontal cortex and parietal cortex. In this work, we developed a novel graph convolutional neural networks (gCNNs) for the analysis of localized anatomic shape and prediction of Gf. Morphologic information of the cortical ribbons and subcortical structures was extracted from T1-weighted MRIs within two independent cohorts, the Adolescent Brain Cognitive Development Study (ABCD; age: 9.93 ± 0.62 years) of children and the Human Connectome Project (HCP; age: 28.81 ± 3.70 years). Prediction combining cortical and subcortical surfaces together yielded the highest accuracy of Gf for both ABCD (R = 0.314) and HCP datasets (R = 0.454), outperforming the state-of-the-art prediction of Gf from any other brain measures in the literature. Across both datasets, the morphology of the amygdala, hippocampus, and nucleus accumbens, along with temporal, parietal and cingulate cortex consistently drove the prediction of Gf, suggesting a significant reframing of the relationship between brain morphology and Gf to include systems involved with reward/aversion processing, judgment and decision-making, motivation, and emotion. 

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4. A preliminary study of threat-anticipatory responding in Latina youth: associations with age, anxiety, and cortical thickness

   https://doi.org/10.1093/scan/nsae065  

   Mullins, Jordan_L; Abend, Rany; Michalska, Kalina_J (October 2024, Social Cognitive and Affective Neuroscience)

   Abstract Variation in prefrontal cortex neuroanatomy has been previously associated with elevated physiological responses to anticipated aversive events. The extent to which such associations extend beyond the specific ecology of treatment-seeking youth from upper-middle socioeconomic backgrounds is unknown. The current study tests the replicability of neuroanatomical correlates of anticipatory responding and the moderating roles of age and anxiety severity in a community sample of Latina girls, a historically underrepresented group exhibiting high levels of untreated anxiety. Forty pre-adolescent Latina girls (MAge = 10.01, s.d. = 1.25, range = 8–12 years) completed a structural magnetic resonance imaging scan. Participants also completed a differential threat and safety learning paradigm, during which skin conductance and subjective fear responding were assessed. Anxiety severity was assessed via the Screen for Child Anxiety Related Emotional Disorders. Ventromedial prefrontal cortex thickness was associated with reduced physiological responsivity to anticipated threat. Age- and anxiety-dependent associations emerged between dorsomedial prefrontal cortex thickness and individual differences in subjective fear responding to anticipated threat. This preliminary study extends work on neuroanatomical contributions to physiological threat responsivity to a community sample of Latina youth and highlights potential considerations for early identification efforts in this population when threat neurocircuitry is still developing. 

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5. Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain

   https://doi.org/10.1111/gbb.12858  

   Latchney, Sarah E; Cadney, Marcell D; Hopkins, Anthony; Garland, Theodore (December 2023, Genes, Brain and Behavior)

   Abstract Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex‐specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non‐selected control (C) line. Through cross‐fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel‐running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression forBdnf,Pde4dandGrin2b. Decreases inBdnfmethylation correlated with significant increases inBdnfgene expression in the hippocampus of HR compared to C mice. Cross‐fostering also influenced the DNA methylation patterns forPde4din the cortex andGrin2bin the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns forAtrxandOxtrin the cortex andAtrxandBdnfin the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early‐life influences to shape adult exercise behavior. 

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