Huge amounts of money are spent every year on unlearning programs--in drug-treatment facilities, prisons, psychotherapy clinics, and schools. Yet almost all of these programs fail, since recidivism rates are high in each of these fields. Progress on this problem requires a better understanding of the mechanisms that make unlearning so difficult. Much cognitive neuroscience evidence suggests that an important component of these mechanisms also dictates success on categorization tasks that recruit procedural learning and depend on synaptic plasticity within the striatum. A biologically detailed computational model of this striatal-dependent learning is described (based on Ashby & Crossley, 2011). The model assumes that a key component of striatal-dependent learning is provided by interneurons in the striatum called the tonically active neurons (TANs), which act as a gate for the learning and expression of striatal-dependent behaviors. In their tonically active state, the TANs prevent the expression of any striatal-dependent behavior. However, they learn to pause in rewarding environments and thereby permit the learning and expression of striatal-dependent behaviors. The model predicts that when rewards are no longer contingent on behavior, the TANs cease to pause, which protects striatal learning from decay and prevents unlearning. In addition, the model predicts that when rewards are partially contingent on behavior, the TANs remain partially paused, leaving the striatum available for unlearning. The results from 3 human behavioral studies support the model predictions and suggest a novel unlearning protocol that shows promising initial signs of success.
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http://dx.doi.org/10.1037/a0030059 | DOI Listing |
bioRxiv
December 2024
Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, 52242, USA.
Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring.
View Article and Find Full Text PDFEur J Neurosci
December 2024
University of Iowa, USA.
17β-Estradiol (E2) is a sex hormone that acts on many brain regions to produce changes in neuronal activity and learning. A key brain region sensitive to E2 is the dorsal striatum (also called caudate-putamen), which controls motor behaviour, goal-directed learning and habit learning. In adult rodents, oestrogen receptors (ERs) in the dorsal striatum are localized to the plasma membrane and include ERα, ERβ and G protein-coupled ER (GPER).
View Article and Find Full Text PDFJ Neurosci
November 2024
Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720
is a high-confidence autism spectrum disorder (ASD) risk gene, and mutations in lead to a neurodevelopmental disorder (NDD) that presents with epilepsy, ASD, motor developmental delay, and intellectual disability. codes for Ras/Rap GTP-ase activating protein SynGAP (SynGAP). SynGAP is located in the postsynaptic density of glutamatergic synapses and regulates glutamate receptor trafficking in an activity-dependent manner.
View Article and Find Full Text PDFCommun Biol
November 2022
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
LRRK2 mutations are closely associated with Parkinson's disease (PD). Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations-G2019S and R1441C-we investigated how LRRK2 mutations altered striatal physiology.
View Article and Find Full Text PDFFront Neurosci
October 2022
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Hearing loss is a chronic health condition that affects millions of people worldwide. In addition to age-related hearing impairment, excessive noise exposure is a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, epidemiological studies have identified hearing loss as a major risk factor for age-related cognitive decline, including dementia.
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