Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Dopamine (DA) type 1 receptor (D1R) signaling in the striatum presumably regulates neuronal excitability and reward-related behaviors through PKA. However, whether and how D1Rs and PKA regulate neuronal excitability and behavior remain largely unknown. Here, we developed a phosphoproteomic analysis method to identify known and novel PKA substrates downstream of the D1R and obtained more than 100 candidate substrates, including Rap1 GEF (Rasgrp2). We found that PKA phosphorylation of Rasgrp2 activated its guanine nucleotide-exchange activity on Rap1. Cocaine exposure activated Rap1 in the nucleus accumbens in mice. The expression of constitutively active PKA or Rap1 in accumbal D1R-expressing medium spiny neurons (D1R-MSNs) enhanced neuronal firing rates and behavioral responses to cocaine exposure through MAPK. Knockout of Rap1 in the accumbal D1R-MSNs was sufficient to decrease these phenotypes. These findings demonstrate a novel DA-PKA-Rap1-MAPK intracellular signaling mechanism in D1R-MSNs that increases neuronal excitability to enhance reward-related behaviors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuron.2015.12.019 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adverse gestational environment configures a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety.
Cell Rep
September 2025
Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:
An adverse gestational environment is a risk factor for the development of psychiatric disorders. Although studies have implicated modifications in neuronal DNA and chromatin, how these changes come about and lead to abnormal behaviors is not known. We sought to identify persistent DNA/chromatin and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to anxiety.
View Article and Find Full Text PDFEffects of anaesthesia on cognitive function in young and aged mice: Role of c-Fos expression in hippocampal neuron excitability.
Rev Esp Anestesiol Reanim (Engl Ed)
September 2025
Department of Neurology, Xuzhou Central Hospital, Xuzhou, China. Electronic address:
Objective: This study aims to investigate the effects of anaesthesia and surgical procedures on the cognitive function of both young and aged mice. It will also explore the role and mechanisms of c-Fos expression in altering hippocampal neuron excitability and its relationship with perioperative neurocognitive disorders in mice.
Methods: In this study, we used a murine laparotomy model to assess cognitive behavioural changes in both young and aged mice at 1, 3, and 7 days post-surgery.
Applying high-density surface EMG to the study of neuromuscular disorders: a systematic review.
Clin Neurophysiol
August 2025
University of Queensland, Centre for Clinical Research, Herston, QLD, Australia; Royal Brisbane & Women's Hospital, Herston, QLD, Australia. Electronic address:
Objective: High-density surface electromyography (HD-sEMG) is a non-invasive and quantitative tool for studying neuromuscular disorders, enabling assessments of muscle excitation, motor unit (MU) characteristics and firing patterns. This systematic review reports the published evidence on the clinical applications of HD-sEMG across neuromuscular disorders, identifying the range of disorders studied, indexes utilized, and gaps in the literature.
Methods: Systematic searches in PubMed and Scopus identified 200 studies, of which 55 met the inclusion criteria.
Aging-related adaptations of metabotropic glutamate receptors within the CA3 region of the rat hippocampus.
Neurobiol Aging
September 2025
Departamento de Farmacobiología. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 14330, Mexico. Electronic address:
The physiological decline associated with aging is often accompanied by a progressive deterioration in cognitive processing abilities driven by a series of cellular dysfunctions that remain poorly understood. In the hippocampus, a critical area for learning and memory, aging affects the functional expression of ionotropic and metabotropic receptors, including the metabotropic glutamate receptors (mGluRs). mGluRs play a critical role in multiple cellular functions, including modulation of ion channels and intrinsic excitability, synaptic transmission, and induction of synaptic plasticity, processes considered part of the cellular substrates for learning and memory.
View Article and Find Full Text PDFEstrogen receptor beta in lateral habenula mediates antidepressant effects of estrogen in postpartum-hormone-withdrawal-induced depression.
Mol Psychiatry
September 2025
Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai, China.
Dramatic drop in reproductive hormone, especially estrogen level, from pregnancy to postpartum period is known to contribute to postpartum depression (PPD), but the underlying mechanism and the role of the estrogen receptors (ERs) in this process were unclear. Here, we used an estrogen-withdrawal-induced PPD model following hormone simulated pregnancy (HSP) in female Sprague-Dawley rats to induce depressive-like behaviors. After estrogen withdrawal, we observe an up-regulation of astrocyte-specific potassium channel (Kir4.
View Article and Find Full Text PDF