{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:57:42Z","timestamp":1785430662275,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,16]]},"group-title":"Neuroscience","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U01AA025932"],"award-info":[{"award-number":["U01AA025932"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA027768"],"award-info":[{"award-number":["R01AA027768"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA030293"],"award-info":[{"award-number":["R01AA030293"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Basal forebrain cholinergic neurons regulate cortical activity and cognition and are vulnerable in Alzheimer\u2019s disease (AD). However, the upstream circuits controlling projection-defined basal forebrain cholinergic populations remain incompletely understood. Here, we used projection-specific rabies-mediated monosynaptic tracing to map whole-brain inputs to medial prefrontal cortex (mPFC)-projecting cholinergic neurons in the nucleus basalis of Meynert (NBM) and horizontal limb of the diagonal band of Broca (HDB). mPFC-projecting NBM and HDB cholinergic neurons received broad but distinct input patterns. NBM cholinergic neurons received prominent striatal input, including input from D1-expressing medium spiny neurons, whereas HDB cholinergic neurons showed proportionally weaker striatal input and broader non-striatal contributions. Optogenetic electrophysiology confirmed that striatal inputs formed monosynaptic GABAergic inhibitory synapses onto NBM cholinergic neurons. This inhibitory transmission was weakened in 5xFAD mice, indicating impairment of a striatal\u2013NBM inhibitory circuit in an AD mouse model. Together, these findings reveal subregion-specific input organization of mPFC-projecting basal forebrain cholinergic neurons and identify a vulnerable striatal\u2013NBM circuit in AD.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>Whole-brain rabies tracing reveals input organization of mPFC-projecting BF cholinergic neurons.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>NBM and HDB cholinergic neurons projecting to mPFC show distinct monosynaptic input profiles.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Striatal D1-MSNs are a major input source to mPFC-projecting NBM cholinergic neurons.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Striatal\u2013NBM inhibitory transmission is functionally impaired in 5xFAD mice.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.11.731708","type":"posted-content","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:45:13Z","timestamp":1781624713000},"source":"Crossref","is-referenced-by-count":0,"title":["Subregion-Specific Input Organization of Prefrontal-Projecting Basal Forebrain Cholinergic Neurons and Weakened Striatal\u2013NBM Inhibitory Transmission in 5xFAD mice"],"prefix":"10.64898","author":[{"given":"Yufei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"},{"name":"Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fernaine","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"},{"name":"Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0085-4722","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Naresh K. 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