Patterns of Coupled Theta Activity in Amygdala-Hippocampal-Prefrontal Cortical Circuits during Fear Extinction

Signals related to fear memory and extinction are processed within brain pathways involving the lateral amygdala (LA) for formation of aversive stimulus associations, the CA1 area of the hippocampus for context-dependent modulation of these associations, and the infralimbic region of the medial prefrontal cortex (mPFC) for extinction processes. While many studies have addressed the contribution of each of these modules individually, little is known about their interactions and how they function as an integrated system. Here we show, by combining multiple site local field potential (LFP) and unit recordings in freely behaving mice in a fear conditioning paradigm, that theta oscillations may provide a means for temporally and functionally connecting these modules. Theta oscillations occurred with high specificity in the CA1-LA-mPFC network. Theta coupling increased between all areas during retrieval of conditioned fear, and declined during extinction learning. During extinction recall, theta coupling partly rebounded in LA-mPFC and CA1-mPFC, and remained at a low level in CA1-LA. Interfering with theta coupling through local electrical microstimulation in CA1-LA affected conditioned fear and extinction recall depending on theta phase. These results support the hypothesis that theta coupling provides a means for inter-areal coordination in conditioned behavioral responsiveness. More specifically, theta oscillations seem to contribute to a population code indicating conditioned stimuli during recall of fear memory before and after extinction

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Memory formation, reconsolidation, extinction and forgetting in lymnaea stagnalis

Bibliography: p. 203-227Some pages are in colour

Improving MICU O:E mortality ratio

"Improve physician and nursing documentation to capture severity of illness, comorbidity, and risk of mortality for Medicare payer patients with diagnosis of sepsis, respiratory failure, and poisoning in patients: greater than 18 years of age; greater than or equal to 1 day of ICU care, and are discharged from either Pulmonary/Critical Care, Internal Medicine, or Family Medicine. As measured by: 10 percent improvement in observed to expected mortality ratio, comorbidity and major comorbidity (CC/MCC) capture rates through chart review of all patients and education of clinicians, and increase reimbursement through increase capture of MCCs and CCs."--Aim statement

Changes in microglial morphology following an acute stressor in male and female rats

Changes in microglial morphology following an acute stressor in male and female rats Houston Meminger1*, Jadebrielle Bennesh1*, Mikayla Voglewede 1Department of Psychological Sciences, Purdue University *Contributed equally Post-traumatic stress disorder (PTSD) is characterized by generalized fear responses to previously non-aversive stimuli following exposure to a traumatic event. Despite incidence rates for traumatic events being nearly equal between the sexes, women are twice as likely to develop PTSD. To explore these sex differences, we are examining how microglia in the prefrontal cortex respond to stress in both male and female Long Evans rats. Specifically, male and female rats were exposed to 15 1.0 mA unsignaled footshocks over the course of 90 min—control animals were exposed to the context without any shock delivery. 9 or 15 days after this acute stressor, rats were euthanized, and their brains were removed and sectioned for immunohistochemical staining with IBA1 antibodies and DAB. Preliminary data demonstrate differences in microglial morphology between 9 and 15 days after exposure to an acute stressor in male rats, and current analyses are evaluating whether these differences are also occurring in females. These morphological analyses will determine if microglia are operating differently between males and females in response to stress, which may serve as a stepping stone for future research investigating sex differences in developing PTSD