{"doi":"10.3389/fpsyt.2022.854494","title":"The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes","abstract":"Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.","journal":"Frontiers in Psychiatry","year":2022,"id":248126,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419906,"name":"Daniela Franco","orcid":"0000-0002-1867-8528","position":1,"is_corresponding":false},{"id":562963,"name":"Shannon L. Cole","orcid":"0000-0003-3377-5876","position":2,"is_corresponding":false},{"id":811647,"name":"Gessynger Morais‐Silva","orcid":"0000-0002-1387-9881","position":3,"is_corresponding":false},{"id":562964,"name":"Ramesh Chandra","orcid":"0000-0002-4473-5071","position":4,"is_corresponding":false},{"id":336017,"name":"Megan E. Fox","orcid":"0000-0003-3177-831X","position":5,"is_corresponding":false},{"id":264361,"name":"Sergio D. Iñiguez","orcid":"0000-0001-5748-4219","position":6,"is_corresponding":false},{"id":886837,"name":"César Renato Sartori","orcid":"0000-0003-2713-3914","position":7,"is_corresponding":false},{"id":69430,"name":"Mary Kay Lobo","orcid":"0000-0002-9419-2079","position":8,"is_corresponding":false},{"id":811648,"name":"Marco Pagliusi","orcid":"0000-0002-8379-9131","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:24:09.893688Z","pmid":"35722560","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}