The Role of the Amygdala, Retrosplenial Cortex, and Medial Prefrontal Cortex in Trace Fear Extinction and Reconsolidation

A wealth of research has outlined the neural circuits responsible for the consolidation, reconsolidation, and extinction of standard delay fear conditioning, in which awareness is not required for learning. Far less is understood about the neural circuit supporting more complex, explicit associations. Trace fear conditioning is considered to be a rodent model of explicit fear because it relies on the cortex and hippocampus and requires explicit contingency awareness in humans for successful acquisition. In the current set of studies, we aimed to better characterize the neural circuit supporting the consolidation, reconsolidation, and extinction of trace fear in order to better understand how explicit associations are stored and updated in the brain. We found that trace fear extinction relies on NMDA receptors in the retrosplenial cortex and prelimibic medial prefrontal cortex, rather than the amygdala, which is required for extinguishing delay fear. NMDA receptors in the infralimbic medial prefrontal cortex, on the other hand, were involved in the extinction of both delay and trace associations. These results suggest that trace fear is consolidated and stored in a distributed cortical manner, relying in part on the retrosplenial and prelimbic cortices. The amygdala, on the other hand, is responsible for the long-term storage of delay, but not trace associations. Consistent with this, our next study demonstrated that protein synthesis in the retrosplenial cortex was required for the acquisition or early consolidation of trace, but not delay fear. Finally, we demonstrated that a reconsolidation-dependent updating procedure can be used to shift a relatively complex trace fear association to the more basic neural circuit that supports delay fear. Together, these results provide a more complete understanding of the neural circuit supporting trace fear, demonstrating that this type of complex association relies on multiple cortical structures for extinction, including the retrosplenial and prelimbic cortices, instead of the amygdala. Our results also demonstrate that updating procedures can reorganize the neural circuit supporting a complex trace fear memory so that the association relies on a simpler set of structures

NR2A- and NR2B-containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

Activation of N-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially regulate these two fear memories. Here we show that NR2A-containing NMDARs mediate trace, delay, and contextual fear memories, but NR2B-containing NMDARs are required only for trace conditioning, consistent with a role for PL mPFC in working memory

Opracowanie i właściwości psychometryczne polskiej wersji Skali Samokontroli

Self-control was recognized as an important function of the human self, whereby the person can override or alter its impulses, moods, emotions, and behaviors. Tangney, Baumeister, and Boone developed a scale for the measurement of individual differences in self-control — Self-Control Scale (S-CS). This article presents the adaptation of S-CS to Polish conditions, which was started when there was no method for testing self-control in Poland. The aim of the present study was fivefold: (1) development of the Polish version of the Self-Control Scale (S-CS-Pv); (2) examination of the properties of the SC-S-Pv’s items; (3) estimation of the SC-S-Pv’s reliability; (4) comparison of the S-CS-Pv’s internal structure with the original scale, and (5) assessment of the SC-S-Pv’s content validity. In the process of S-CS adaptation, a back-translation procedure was used. Polish adaptation is a reliable method with validity proven, both by correlation with other tests and by group comparisons. However, the factor analysis results suggested its multidimensionality.Samokontrola jest ważną funkcją ludzkiego Ja, dzięki której osoba może przezwyciężyć lub zmienić swoje impulsy, nastroje, emocje i zachowania. Tangney, Baumeister i Boone opracowali skalę do pomiaru indywidualnych różnic w samokontroli – Skalę Samokontroli (Self-Control Scale, S-CS). W artykule przedstawiono adaptację S-CS do polskich warunków kulturowych, nad którą prace rozpoczęto, gdy nie było metody pomiaru samokontroli w Polsce. Cele niniejszego badania były następujące: 1) opracowanie polskiej wersji Skali Samokontroli (S-CS-Pv); 2) ocena właściwości pozycji testowych SC-S-Pv; 3) oszacowanie rzetelności SC-S-Pv; 4) porównanie wewnętrznej struktury S-CS-Pv z oryginalną skalą; 5) ocena trafności teoretycznej SC-S-Pv. W procesie adaptacji S-CS zastosowano procedurę tłumaczenia zwrotnego. Polska adaptacja jest rzetelną metodą o trafności wykazanej zarówno przez korelację z innymi testami, jak i przez porównania grup. Wyniki analizy czynnikowej sugerują jednak jej strukturę wielowymiarową

Psychometric Properties of the Polish Version of the Passion Scale

RESEARCH OBJECTIVE: The aim of the article is to present the Polish adaptation of the Vallerand’s Passion Scale. THE RESEARCH PROBLEM AND METHODS: Does the scale have a two-factore structure in accordance with the theoretical model and the original version? Is the theoretical validity satisfactory? Is the reliability of the scale satisfactory? THE PROCESS OF ARGUMENTATION: The validation included back translation, estimating reliability and theoretical validity. RESEARCH RESULTS: Exploratory factor analysis revealed the dual model of the passion, indicating the existence of harmonious and obsessive passion. The results of the confirmatory analysis are also discussed. The Scale has a good reliability of the subscales. The theoretical validity of the Scale was verified by correlations between types of passion and identity interest and flow. CONCLUSIONS, INNOVATIONS AND RECOMMENDATIONS: The results of validation are satisfactory and the Polish version of the Scale can be applied in scientific research

Biobank Łódź® – population based biobank at the University of Łódź, Poland

Biobank Laboratory of the University of Łódź is a unit in the organizational structure of the De- partment of Molecular Biophysics at the Faculty of Biology and Environmental Protection. It was established in 2014 as one of the results of the TESTOPLEK project. One of the main goals of the unit is to collect and share biological material of human origin and related clinical and survey data. Moreover, Biobank Laboratory conducts work in the field of genetics and molecular biology on human biological material. Biobank Laboratory gathers over 40.000 samples such as DNA, FFPE, saliva, together with their data. Data about its material is available for researchers in directories e.g. BBMRI-ERIC Directory 4.0. Since 2014, the unit belongs to the national Consortium BBMRI.pl, and since 2017 it executes a project entitled Research Infrastructure for Biobanks and Biomolecular Resources BBMRI-ERIC, co-creating the Polish Network of Biobanks. Biobank Laboratory is focused on coopera- tion with domestic and foreign scientific institutions and medical units, as well as entities from the local, business and public sector

Zeta Inhibitory Peptide attenuates learning and memory by inducing NO-mediated downregulation of AMPA receptors

Zeta inhibitory peptide (ZIP), a PKMζ inhibitor, is widely used to interfere with the main- tenance of acquired memories. ZIP is able to erase memory even in the absence of PKMζ, via an unknown mechanism. We found that ZIP induces redistribution of the AMPARGluA1 in HEK293 cells and primary cortical neurons, and decreases AMPAR-mediated currents in the nucleus accumbens (NAc). These effects were mimicked by free arginine or by a modified ZIP in which all but the arginine residues were replaced by alanine. Redistribution was blocked by a peptidase-resistant version of ZIP and by treatment with the nitric oxide (NO)- synthase inhibitor L-NAME. ZIP increased GluA1-S831 phosphorylation and ZIP-induced redistribution was blocked by nitrosyl-mutant GluA1-C875S or serine-mutant GluA1-S831A. Introducing the cleavable arginine-alanine peptide into the NAc attenuated expression of cocaine-conditioned reward. Together, these results suggest that ZIP may act as an arginine donor, facilitating NO-dependent downregulation of AMPARs, thereby attenuating learning and memory

Digoxin, an Overlooked Agonist of RORγ/RORγT

Digoxin was one of the first identified RORγT receptor inverse agonists inhibiting the differentiation of Th17 cells. However, this compound exhibits inhibitory activity at relatively high concentrations that mediate cytotoxic effects. We previously identified several cardenolides that are structurally similar to digoxin that were able to induce RORγ/RORγT-dependent transcription. These observations encouraged us to reanalyze the effects of digoxin on RORγ/RORγT-dependent transcription at low, noncytotoxic concentrations. Digoxin induced RORγ/RORγT-dependent transcription in HepG2 and Th17 cells. Furthermore, analysis of the transcriptomes of Th17 cells cultured in the presence of digoxin revealed the induction of the expression of numerous Th17-specific genes, including IL17A/F, IL21, IL22, IL23R, CCR4, and CCR6. Thus, our study, which includes data obtained from intact cells, indicates that digoxin, similar to other cardenolides, is a potent RORγ/RORγT receptor activator and that its structure may serve as a starting point for the design of dedicated molecules that can be used in the development of adoptive cell therapy (ACT)

rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10–5; beta: − 0.0458, 95% confidence interval (CI) − 0.0732 : − 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10–4; beta: − 0.0573, CI − 0.0947 : − 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.The POPULOUS database was the outcome of the project TESTOPLEK which was funded by the Innovative Economy Operational Programme provided by the European Regional Development Fund 2007–2013. This source had no involvement in the study other than funding for the database