Hannestad JO, Cosgrove KP, Dellagioia NF, Perkins E, Bois F, Bhagwagar Z, et al. Changes in the cholinergic system between bipolar depression and euthymia as measured with [123I]5IA single photon emission computed tomography. Biol Psychiatry. 2013;74:768–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Esterlis I, Hannestad JO, Bois F, Sewell RA, Tyndale RF, Seibyl JP, et al. Imaging changes in synaptic acetylcholine availability in living human subjects. J Nucl Med. 2013;54:78–82.

Article  PubMed  Google Scholar 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ. A cholinergic-adrenergic hypothesis of mania and depression. Lancet. 1972;2:632–5.

Janowsky D, Khaled El-Yousef M, Davis J, Hubbard B, Sekerke HJ. Cholinergic reversal of manic symptoms. Lancet. 1972;299:1236–7.

Article  Google Scholar 

Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, et al. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology. 2018;43:2118–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mineur YS, Ernsten C, Islam A, Maibom KL, Picciotto MR. Hippocampal knockdown of α2 nicotinic or m1 muscarinic acetylcholine receptors in C57BL /6j male mice impairs cued fear conditioning. Genes, Brain Behav. 2020;9:1–10.

Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, et al. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proc Natl Acad Sci. 2013;110:3573–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mineur YS, Picciotto MR. The role of acetylcholine in negative encoding bias: Too much of a good thing? Eur J Neurosci. 2019;53:114–25.

Addy NA, Nunes EJ, Wickham RJ. Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test. Behav Brain Res. 2015;288:54–62.

Mineur YS, Fote GM, Blakeman S, Cahuzac ELM, Newbold SA, Picciotto MR. Multiple nicotinic acetylcholine receptor subtypes in the mouse amygdala regulate affective behaviors and response to social stress. Neuropsychopharmacology. 2016;41:1579–87.

Article  CAS  PubMed  Google Scholar 

Fernandes SS, Koth AP, Parfitt GM, Cordeiro MF, Peixoto CS, Soubhia A, et al. Enhanced cholinergic-tone during the stress induce a depressive-like state in mice. Behav Brain Res. 2018;347:17–25.

Article  CAS  PubMed  Google Scholar 

Crouse RB, Kim K, Batchelor HM, Girardi EM, Kamaletdinova R, Chan J, et al. Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency. eLife. 2020;9:e7335.

Hasselmo ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006;16:710–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Teles-Grilo Ruivo LM, Baker KL, Conway MW, Kinsley PJ, Gilmour G, Phillips KG, et al. Coordinated acetylcholine release in prefrontal cortex and hippocampus is associated with arousal and reward on distinct timescales. Cell Rep. 2017;18:905–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Obermayer J, Luchicchi A, Heistek TS, De Kloet SF, Terra H, Bruinsma B, et al. Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention. Nat Commun. 2019;10:1–14.

Dalley JW, Theobald DE, Bouger P, Chudasama Y, Cardinal RN, Robbins TW. Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex. Cereb Cortex. 2004;14:922–32.

Article  PubMed  Google Scholar 

Power SK, Venkatesan S, Lambe EK. Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex. Neuropsychopharmacology. 2023;48:671–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Picciotto M, Addy N, Mineur Y, Brunzell D. It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog Neurobiol. 2008;84:329–42.

Article  CAS  PubMed  Google Scholar 

Xu L, Liu Y, Long J, He X, Xie F, Yin Q, et al. Loss of spines in the prelimbic cortex is detrimental to working memory in mice with early-life adversity. Mol Psych. 2023;28:3444–58.

Jing M, Li Y, Zeng J, Huang P, Skirzewski M, Kljakic O, et al. An optimized acetylcholine sensor for monitoring in vivo cholinergic activity. Nat Methods. 2020;17:1139–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caldarone BJ, George TP, Zachariou V, Picciotto MR. Gender differences in learned helplessness behavior are influenced by genetic background. Pharmacol Biochem Behav. 2000;66:811–7.

Article  CAS  PubMed  Google Scholar 

Abdulla ZI, Pennington JL, Gutierrez A, Skelton MR. Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness. Behavioural Brain Res. 2020;377:112254.

Article  CAS  Google Scholar 

Bloem B, Schoppink L, Rotaru DC, Faiz A, Hendriks P, Mansvelder HD, et al. Topographic mapping between basal forebrain cholinergic neurons and the medial prefrontal cortex in mice. J Neurosci. 2014;34:16234–46.

Article  PubMed  PubMed Central  Google Scholar 

Bland JM, Altman DG. The logrank test. BMJ. 2004;328:1073.

Article  PubMed  PubMed Central  Google Scholar 

Chourbaji S, Zacher C, Sanchis-Segura C, Dormann C, Vollmayr B, Gass P. Learned helplessness: validity and reliability of depressive-like states in mice. Brain Res Protoc. 2005;16:70–8.

Article  CAS  Google Scholar 

Marques DB, Ruggiero RN, Bueno-Junior LS, Rossignoli MT, Leite JP. Prediction of learned resistance or helplessness by hippocampal-prefrontal cortical network activity during stress. J Neurosci. 2021:42;81–96.

Togashi H, Matsumoto M, Yoshioka M, Hirokami M, Tochihara M, Saito H. Acetylcholine measurement of cerebrospinal fluid by in vivo microdialysis in freely moving rats. Jpn J Pharmacol. 1994;66:67–74.

Article  CAS  PubMed  Google Scholar 

Kaufer D, Friedman A, Seidman S, Soreq H. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature. 1998;393:373–7.

Article  CAS  PubMed  Google Scholar 

Mark GP, Rada PV, Shors TJ. Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala. Neuroscience. 1996;74:767–74.

Article  CAS  PubMed  Google Scholar 

Mineur YS, Mose TN, Vanopdenbosch L, Etherington IM, Ogbejesi C, Islam A, et al. Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs. Mol Psychiatry. 2022;27:1829–38.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rienda B, Elexpe A, Tolentino-Cortez T, Gulak M, Bruzos-Cidón C, Torrecilla M, et al. Analysis of acetylcholinesterase activity in cell membrane microarrays of brain areas as a screening tool to identify tissue specific inhibitors. Analytica. 2021;2:25–36.

Article  Google Scholar 

Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression-like behaviour in C57BL/6J mice. Br J Pharmacol. 2018;175:1903–14.

Article  CAS  PubMed  Google Scholar 

Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, et al. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. J Clin Investig. 2016;126:2482–94.

Article  PubMed  PubMed Central  Google Scholar 

Navarria A, Wohleb ES, Voleti B, Ota KT, Dutheil S, Lepack AE, et al. Rapid antidepressant actions of scopolamine: Role of medial prefrontal cortex and M1-subtype muscarinic acetylcholine receptors. Neurobiol Dis. 2015;82:254–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fogaca MV, Wu M, Li C, Li XY, Duman RS, Picciotto MR. M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses. Neuropsychopharmacology. 2023;48:1277–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, et al. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proc Natl Acad Sci USA. 2015;112:8106–11.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu RJ, Ota KT, Dutheil S, Duman RS, Aghajanian GK. Ketamine Strengthens CRF-Activated Amygdala Inputs to Basal Dendrites in mPFC Layer V Pyramidal Cells in the Prelimbic but not