How Dopamine Enables Learning from Aversion.

Dopamine is heavily studied for its role in reward learning, but it is becoming increasingly appreciated that dopamine can also enable learning from aversion. Dopamine neurons modulate their firing and neurotransmitter release patterns in response to aversive outcomes. However, there is considerable heterogeneity in the timing and directionality of the modulation.

Gynecologic health care for LGBTQIA+ people.

Gender relations are a set of socially determined norms and rules that assign values, characteristics, and expectations to individuals based on their biological sex. These aspects also influence the clinician-patient relationship, since it has been for a long time based on cisheteronormativity. However, this attitude alienated the LGBTQIA+ community from health services.

T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery.

Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors], a system to rapidly deconvolute CD4 and CD8 TCRs and targets physiologically processed and presented by an individual's unmanipulated, complete human leukocyte antigen (HLA) haplotype. Combining a highly sensitive TCR signaling reporter with an antigen processing system to overcome previously undescribed limitations to target expression, T-FINDER both robustly identifies unknown peptide:HLA ligands from antigen libraries and rapidly screens and functionally validates the specificity of large TCR libraries against known or predicted targets.

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient.

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells.

Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson's disease progression.

Dopamine neurons in the substantia nigra pars compacta (SNc) synthesize and release dopamine, a critical neurotransmitter for movement and learning. SNc dopamine neurons degenerate in Parkinson's Disease (PD), causing a host of motor and non-motor symptoms. Here, we review recent conceptual advances in our basic understanding of the dopamine system - including our rapidly advancing knowledge of dopamine neuron heterogeneity - with special attention to their importance for understanding PD.

Chronically dysregulated corticosterone impairs dopaminergic transmission in the dorsomedial striatum by sex-divergent mechanisms.

Major depressive disorder (MDD) is a leading cause of disability worldwide. Individuals with MDD exhibit decreased motivation and deficits in reward processing. In a subset of MDD patients, chronic dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis occurs, resulting in increased levels of the 'stress hormone' cortisol during the normal rest period (i.

Cognitive-behavioral group therapy for women with hypoactive sexual desire: A pilot randomized study.

Background: Hypoactive Sexual Desire Disorder (HSDD) is a very prevalent sexual problem, with limited options for treatment. Given that psychological factors are major contributors to the disorder, a therapy such as Cognitive-Behavioral Therapy (CBT) may be useful to treat HSDD.

Objective: To evaluate the effects of group CBT on women with HSDD.

Dopamine signaling in the dorsomedial striatum promotes compulsive behavior.

Compulsive behavior is a defining feature of disorders such as substance use disorders. Current evidence suggests that corticostriatal circuits control the expression of established compulsions, but little is known about the mechanisms regulating the development of compulsions. We hypothesized that dopamine, a critical modulator of striatal synaptic plasticity, could control alterations in corticostriatal circuits leading to the development of compulsions (defined here as continued reward seeking in the face of punishment).

MultiEditR: The first tool for the detection and quantification of RNA editing from Sanger sequencing demonstrates comparable fidelity to RNA-seq.

We present MultiEditR (Multiple Edit Deconvolution by Inference of Traces in R), the first algorithm specifically designed to detect and quantify RNA editing from Sanger sequencing (z.umn.edu/multieditr).

Dopamine, Updated: Reward Prediction Error and Beyond.

Dopamine neurons have been intensely studied for their roles in reinforcement learning. A dominant theory of how these neurons contribute to learning is through the encoding of a reward prediction error (RPE) signal. Recent advances in dopamine research have added nuance to RPE theory by incorporating the ideas of sensory prediction error, distributional encoding, and belief states.

Parvalbumin and Npas1 Pallidal Neurons Have Distinct Circuit Topology and Function.

The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. Phasic changes in the activity of GPe neurons during movement and their alterations in Parkinson's disease (PD) argue that the GPe is important in motor control. Parvalbumin-positive (PV) neurons and Npas1 neurons are the two principal neuron classes in the GPe.

C-to-U RNA Editing: From Computational Detection to Experimental Validation.

The AID/APOBEC family of enzymes are cytidine deaminases that act upon DNA and RNA. Among APOBECs, the best characterized family member to act on RNA is the enzyme APOBEC1. APOBEC1-mediated RNA editing plays a key role in lipid metabolism and in maintenance of brain homeostasis.

Mycobacterium tuberculosis cords within lymphatic endothelial cells to evade host immunity.

The ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. Here, we show that several M.

Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning.

The central amygdala (CeA) orchestrates adaptive responses to emotional events. While CeA substrates for defensive behaviors have been studied extensively, CeA circuits for appetitive behaviors and their relationship to threat-responsive circuits remain poorly defined. Here, we demonstrate that the CeA sends robust inhibitory projections to the lateral substantia nigra (SNL) that contribute to appetitive and aversive learning in mice.

Interfacing behavioral and neural circuit models for habit formation.

Habits are an important mechanism by which organisms can automate the control of behavior to alleviate cognitive demand. However, transitions to habitual control are risky because they lead to inflexible responding in the face of change. The question of how the brain controls transitions into habit is thus an intriguing one.

The cerebellum shows its stripes.

New studies examine how the different sub-structures in the cerebellum are organized to receive information during complex behavioral tasks.