{"doi":"10.1101/2021.04.20.440613","title":"Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control","abstract":"Summary Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant-conditioning via lever-press for food reward-training in mice induces excitatory synapse formation onto a subset of Anterior Cingulate Cortex neurons projecting to the dorsomedial striatum (ACC ->DMS ). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ-1 in the adult ACC ->DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation did not impact learning but instead resulted in a profound increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC ->DMS neurons rescued or phenocopied the behaviors of the α2δ-1 cKO mice highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":223918,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":825713,"name":"Oluwadamilola O. Lawal","orcid":"0000-0001-5921-4693","position":1,"is_corresponding":false},{"id":562099,"name":"Kristina Sakers","orcid":"0000-0001-8853-053X","position":2,"is_corresponding":false},{"id":825714,"name":"Shiyi Wang","orcid":"0000-0003-3433-3025","position":3,"is_corresponding":false},{"id":351417,"name":"Namsoo Kim","orcid":"0000-0003-3083-8835","position":4,"is_corresponding":false},{"id":400774,"name":"Alexander Friedman","orcid":null,"position":5,"is_corresponding":false},{"id":825715,"name":"Sarah A. Johnson","orcid":"0000-0003-3392-0535","position":6,"is_corresponding":false},{"id":825716,"name":"Chaichontat Sriworarat","orcid":"0000-0002-1917-3409","position":7,"is_corresponding":false},{"id":377377,"name":"Ryan N. Hughes","orcid":"0000-0002-4999-0215","position":8,"is_corresponding":false},{"id":303897,"name":"Scott H. Soderling","orcid":"0000-0001-7808-197X","position":9,"is_corresponding":false},{"id":825717,"name":"Il Hwan Kim","orcid":"0000-0003-4166-6303","position":10,"is_corresponding":false},{"id":351424,"name":"Henry H. Yin","orcid":"0000-0003-1546-6850","position":11,"is_corresponding":false},{"id":247144,"name":"Çağla Eroğlu","orcid":"0000-0002-7204-0218","position":12,"is_corresponding":false},{"id":813471,"name":"Francesco Paolo Ulloa Severino","orcid":"0000-0003-3725-9713","position":0,"is_corresponding":true}],"reference_count":144,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:14.760456Z","pmid":null,"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":[]}