Heterogeneity of dopamine neuron activity across traits and states

Midbrain dopamine neurons fire irregularly, with interspersed clusters of high-frequency spikes, commonly called ‘bursts’. In this review we examine such heterogeneity in activity, and provide insight into how it can participate in psychiatric conditions such as drug addiction. We first describe several techniques used to evaluate dopamine neuron activity, and comment on the different measures that each provides. We next describe the activity of dopamine neurons in ‘basal’ conditions. Specifically, we discuss how the use of anesthesia and reduced preparations may alter aspects of dopamine cell activity, and how there is heterogeneity across species and regions. We also describe how dopamine cell firing changes throughout the peri-adolescent period and how dopamine neuron activity differs across the population. In the final section, we discuss how dopamine neuron activity changes in response to life events. First, we focus attention on drugs of abuse. Drugs themselves change firing activity through a variety of mechanisms, with effects on firing while drug is present differing from those seen after drug discontinuation. We then review how stimuli that are rewarding, aversive, or salient can evoke changes in firing rate and discharge pattern of dopamine neurons, and provide behavioral relevance of dopamine signaling. Finally, we discuss how stress can modulate dopamine neuron firing and how this may contribute to the role that stressful experiences play in psychiatric disorders such as addiction and depression

Additional file 5: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S5. Molecular cytogenetic and phenotypic data of patients with likely pathogenic CNVs (50 patients). [del: deletion, dup: duplication, mat: maternal, pat: paternal, NA: not available, LB: likely benign, LP: likely pathogenic; ID: intellectual disability; ASD: autism spectrum disorder; ADHD: attention deficit hyperactivity disorder; NDD: neurodevelopmental disorders; CHD: congenital heart defect]. (XLS 90 kb

Additional file 2: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S2 Clinical and Phenotypic features of the analyzed sample (293 patients). Total number and percentage as compared to the number of patients for which the single data was available. [ADHD: attention deficit and hyperactivity disorder, ASD: atrial septal defect, CNS: central nervous system, IUGR: intrauterine growth retardation, PDA: patent ductus arteriosus, ToF: Tetralogy of Fallot, VSD: ventral septal defect]. (DOC 90 kb

Additional file 7: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S7. In silico analysis of single CNVs falling in gene-desert regions. Prediction of the influence of CNVs on topologically associating domains (TADs), discrete genomic regions characterized by a high frequency of self-interaction. The presence of noncoding, potentially regulatory elements and the possible positional effect of alterations are also considered. [lincRNA: long intergenic noncoding RNA; H3K27Ac, H3K4Me1: Histone 3 acetilation/methylation, may indicate active regulatory elements; a across TAD boundary; b within TAD]. (XLS 27 kb

Additional file 6: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S6. Correlations between clinical and phenotypic features and aCGH results (likely pathogenic VOUS vs likely benign VOUS + negative aCGH). Statistically significant results for likely pathogenic VOUS are reported in bold [n/N, number of cases with positive variable/number of patients with available data on that variable; NA: not applicable; ADHD: Attention deficit and hyperactivity disorder; ASD: atrial septal defect; CNS: central nervous system; CTG: fetal cardiotocography; IUGR: intrauterine growth restriction; PDA: patent ductus arteriosus; PFO: patent foramen ovale; ToF: Tetralogy of Fallot; VSD: interventricular septal defect]. (DOC 170 kb

Additional file 3: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S3. Correlations between clinical and phenotypic features and aCGH results (pathogenic CNVs vs VOUS). Statistically significant results for pathogenic CNVs are reported in bold and significant data for VOUS are reported in italics. [ADHD: Attention deficit and hyperactivity disorder; ASD: atrial septal defect; CNS: central nervous system; CTG: fetal cardiotocography; IUGR: intrauterine growth restriction; PDA: patent ductus arteriosus; PFO: patent foramen ovale; ToF: Tetralogy of Fallot; VSD: interventricular septal defect]. (DOC 163 kb

Additional file 4: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S4. Correlations between clinical and phenotypic features and aCGH results (pathogenic CNVs vs likely pathogenic CNVs vs likely benign CNVs). All statistically significant features are reported in bold. From post-hoc analysis with Bonferroni correction: *Significant in the comparison of pathogenic and likely benign; §Significant in the comparison of pathogenic and likely pathogenic; ¼Significant in the comparison of likely pathogenic and likely benign. [ADHD: Attention deficit and hyperactivity disorder; ASD: atrial septal defect; CNS: central nervous system; CTG: fetal cardiotocography; IUGR: intrauterine growth restriction; PDA: patent ductus arteriosus; PFO: patent foramen ovale; ToF: Tetralogy of Fallot; VSD: ventricular septal defect]. (DOC 194 kb

Additional file 8: of Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

Table S8. Correlations between phenotypical core features and aCGH results (positive aCGH vs negative aCGH). Statistically significant results for negative aCGH are reported in bold; statistically significant results for positive aCGH are reported in bold and italic. [MCA: multiple congenital anomalies; NDD: neurodevelopmental disorders]. (DOC 49 kb