Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by haploinsufficiency of transcription factor 4 (TCF4). In this work, we focused on the cerebral cortex and investigated in detail the progenitor cell dynamics and the outcome of neurogenesis in a PTHS mouse model. Labeling and quantification of progenitors and newly generated neurons at various time points during embryonic development revealed alterations affecting the dynamic of cortical progenitors since the earliest stages of cortex formation in PTHS mice. Consequently, establishment of neuronal populations and layering of the cortex were found to be altered in heterozygotes subjects at birth. Interestingly, defective layering process of pyramidal neurons was partially rescued by reintroducing TCF4 expression using focal in utero electroporation in the cerebral cortex. Coincidentally with a defective dorsal neurogenesis, we found that ventral generation of interneurons was also defective in this model, which may lead to an excitation/inhibition imbalance in PTHS. Overall, sex-dependent differences were detected with more marked effects evidenced in males compared with females. All of this contributes to expand our understanding of PTHS, paralleling the advances of research in autism spectrum disorder and further validating the PTHS mouse model as an important tool to advance preclinical studies.

Measurement invariance of a Posttraumatic Stress Disorder symptoms measure (PCL-5) in college student and Amazon's mechanical TURK samples.

OBJECTIVE: College student and Amazon's Mechanical TURK (MTURK) samples are regularly utilized in trauma research. Recent literature, however, has criticized these samples for not being generalizable to the general U.S. POPULATION: The purpose of this study was to determine whether college student (n = 255) and MTURK (n = 316) samples are invariant on the Posttraumatic Stress Disorder Checklist for DSM-5. METHOD: Measurement invariance using confirmatory factor analyses was used to determine whether groups are invariant across factor structure, factor loadings, item intercepts, and residual error variances on a given measure of Post-traumatic Stress Disorder (PTSD) symptom severity. RESULTS: Model fit indices indicated the seven-factor Hybrid model was the best-fitting model, but the six-factor Anhedonia model was the most parsimonious model. Both models demonstrated equivalence in factor at the strictest level, indicating MTURK and college student samples are similar in regard to PTSD symptom severity. CONCLUSIONS: These findings provide evidence that these groups can be combined in future studies to increase sample size for trauma research. Only the Anhedonia factor exhibited mean differences between groups, which may be related to true differences between college students and MTURK survey-takers. This study provides further evidence that the findings from trauma studies using these populations are generalizable to each other. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Glycine Receptor Inhibition Differentially Affect Selected Neuronal Populations of the Developing Embryonic Cortex, as Evidenced by the Analysis of Spontaneous Calcium Oscillations.

The embryonic developing cerebral cortex is characterized by the presence of distinctive cell types such as progenitor pools, immature projection neurons and interneurons. Each of these cell types is diverse on itself, but they all take part of the developmental process responding to intrinsic and extrinsic cues that can affect their calcium oscillations. Importantly, calcium activity is crucial for controlling cellular events linked to cell cycle progression, cell fate determination, specification, cell positioning, morphological development and maturation. Therefore, in this work we measured calcium activity in control conditions and in response to neurotransmitter inhibition. Different data analysis methods were applied over the experimental measurements including statistical methods entropy and fractal calculations, and spectral and principal component analyses. We found that developing projection neurons are differentially affected by classic inhibitory neurotransmission as a cell type and at different places compared to migrating interneurons, which are also heterogeneous in their response to neurotransmitter inhibition. This reveals important insights into the developmental role of neurotransmitters and calcium oscillations in the forming brain cortex. Moreover, we present an improved analysis proposing a Gini coefficient-based inequality distribution and principal component analysis as mathematical tools for understanding the earliest patterns of brain activity.