PT  - JOURNAL ARTICLE
AU  - Alexandra Tallafuss
AU  - Sarah J. Stednitz
AU  - Mae Voeun
AU  - Anastasia Levichev
AU  - Johannes Larsch
AU  - Judith Eisen
AU  - Philip Washbourne
TI  - Egr1 Is Necessary for Forebrain Dopaminergic Signaling during Social Behavior
AID  - 10.1523/ENEURO.0035-22.2022
DP  - 2022 Mar 01
TA  - eneuro
PG  - ENEURO.0035-22.2022
VI  - 9
IP  - 2
4099  - http://www.eneuro.org/content/9/2/ENEURO.0035-22.2022.short
4100  - http://www.eneuro.org/content/9/2/ENEURO.0035-22.2022.full
SO  - eNeuro2022 Mar 01; 9
AB  - Finding the link between behaviors and their regulatory molecular pathways is a major obstacle in treating neuropsychiatric disorders. The immediate early gene (IEG) EGR1 is implicated in the etiology of neuropsychiatric disorders, and is linked to gene pathways associated with social behavior. Despite extensive knowledge of EGR1 gene regulation at the molecular level, it remains unclear how EGR1 deficits might affect the social component of these disorders. Here, we examined the social behavior of zebrafish with a mutation in the homologous gene egr1. Mutant fish exhibited reduced social approach and orienting, whereas other sensorimotor behaviors were unaffected. On a molecular level, expression of the dopaminergic biosynthetic enzyme, tyrosine hydroxylase (TH), was strongly decreased in TH-positive neurons of the anterior parvocellular preoptic nucleus. These neurons are connected with basal forebrain (BF) neurons associated with social behavior. Chemogenetic ablation of around 30% of TH-positive neurons in this preoptic region reduced social attraction to a similar extent as the egr1 mutation. These results demonstrate the requirement of Egr1 and dopamine signaling during social interactions, and identify novel circuitry underlying this behavior.