RESEARCH AREAS OF INTEREST
1. The arcuate nucleus (AgRP, POMC) -> paraventricular hypothalamus (PVH) (Mc4r) -> Parabrachial nucleus/pre-LC (PBN/pLC) non-aversive satiety circuit.
RELEVANT PUBLICATIONS
Reviews:
Lowell BB. New Neuroscience of Homeostasis and Drives for Food, Water, and Salt. N Engl J Med. 2019 Jan 31;380(5):459-471. doi: 10.1056/NEJMra1812053. PMID: 30699320.
Andermann ML, Lowell BB. Toward a Wiring Diagram Understanding of Appetite Control. Neuron. 2017 Aug 16;95(4):757-778. doi: 10.1016/j.neuron.2017.06.014. PMID: 28817798; PMCID: PMC5657399
Select research publications:
Douglass AM, Kucukdereli H, Madara JC, Wang D, Wu C, Lowenstein ED, Tao J, Lowell BB. Acute and circadian feedforward regulation of agouti-related peptide hunger neurons. Cell Metab. 2025 Mar 4;37(3):708-722.e5. doi: 10.1016/j.cmet.2024.11.009. Epub 2024 Dec 23. PMID: 39719709; PMCID: PMC11885038.
Douglass AM, Resch JM, Madara JC, Kucukdereli H, Yizhar O, Grama A, Yamagata M, Yang Z, Lowell BB. Neural basis for fasting activation of the hypothalamic-pituitary-adrenal axis. Nature. 2023 Aug;620(7972):154-162. doi: 10.1038/s41586-023-06358-0. Epub 2023 Jul 26. PMID: 37495689; PMCID: PMC11168300.
Li MM, Madara JC, Steger JS, Krashes MJ, Balthasar N, Campbell JN, Resch JM, Conley NJ, Garfield AS, Lowell BB. The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits. Neuron. 2019 May 8;102(3):653-667.e6. doi: 10.1016/j.neuron.2019.02.028. Epub 2019 Mar 14. PMID: 30879785; PMCID: PMC6508999.
Fenselau H, Campbell JN, Verstegen AM, Madara JC, Xu J, Shah BP, Resch JM, Yang Z, Mandelblat-Cerf Y, Livneh Y, Lowell BB. A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH. Nat Neurosci. 2017 Jan;20(1):42-51. doi: 10.1038/nn.4442. Epub 2016 Nov 21. Erratum in: Nat Neurosci. 2017 Jul 26;20(8):1189. doi: 10.1038/nn0817-1189b. PMID: 27869800; PMCID: PMC5191921.
Garfield AS, Li C, Madara JC, Shah BP, Webber E, Steger JS, Campbell JN, Gavrilova O, Lee CE, Olson DP, Elmquist JK, Tannous BA, Krashes MJ, Lowell BB. A neural basis for melanocortin-4 receptor-regulated appetite. Nat Neurosci. 2015 Jun;18(6):863-71. doi: 10.1038/nn.4011. Epub 2015 Apr 27. PMID: 25915476; PMCID: PMC4446192.
Krashes MJ, Shah BP, Madara JC, Olson DP, Strochlic DE, Garfield AS, Vong L, Pei H, Watabe-Uchida M, Uchida N, Liberles SD, Lowell BB. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature. 2014 Mar 13;507(7491):238-42. doi: 10.1038/nature12956. Epub 2014 Feb 2. PMID: 24487620; PMCID: PMC3955843.
Krashes MJ, Shah BP, Koda S, Lowell BB. Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP. Cell Metab. 2013 Oct 1;18(4):588-95. doi: 10.1016/j.cmet.2013.09.009. PMID: 24093681; PMCID: PMC3822903.
Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, Maratos-Flier E, Roth BL, Lowell BB. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011 Apr;121(4):1424-8. doi: 10.1172/JCI46229. PMID: 21364278; PMCID: PMC3069789.
Vong L, Ye C, Yang Z, Choi B, Chua S Jr, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron. 2011 Jul 14;71(1):142-54. doi: 10.1016/j.neuron.2011.05.028. PMID: 21745644; PMCID: PMC3134797.
Tong Q, Ye CP, Jones JE, Elmquist JK, Lowell BB. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci. 2008 Sep;11(9):998-1000. doi: 10.1038/nn.2167. PMID: 19160495; PMCID: PMC2662585.
Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD, Christiansen LM, Edelstein E, Choi B, Boss O, Aschkenasi C, Zhang CY, Mountjoy K, Kishi T, Elmquist JK, Lowell BB. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005 Nov 4;123(3):493-505. doi: 10.1016/j.cell.2005.08.035. PMID: 16269339.
2. Rapid, feed-forward regulation of AgRP hunger neurons by cognitively-processed contextual cues – food cues inhibit AgRP neurons while fasting-related cues activate AgRP neurons.
RELEVANT PUBLICATIONS:
Walker SJ, Lowenstein ED, Douglass AM, Madara JC, Resch JM, Tao J, Lowell BB. A hypothalamic circuit for anticipating future changes in energy balance. bioRxiv [Preprint]. 2025 Sep 27:2025.09.27.678865. doi: 10.1101/2025.09.27.678865. PMID: 41040162; PMCID: PMC12485711.
Berrios J, Li C, Madara JC, Garfield AS, Steger JS, Krashes MJ, Lowell BB. Food cue regulation of AGRP hunger neurons guides learning. Nature. 2021 Jul;595(7869):695-700. doi: 10.1038/s41586-021-03729-3. Epub 2021 Jul 14. PMID: 34262177; PMCID: PMC8522184.
Kim A, Madara JC, Wu C, Andermann ML, Lowell BB. Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality. Elife. 2021 Sep 29;10:e66609. doi: 10.7554/eLife.66609. PMID: 34585668; PMCID: PMC8601670.
Garfield AS, Shah BP, Burgess CR, Li MM, Li C, Steger JS, Madara JC, Campbell JN, Kroeger D, Scammell TE, Tannous BA, Myers MG Jr, Andermann ML, Krashes MJ, Lowell BB. Dynamic GABAergic afferent modulation of AgRP neurons. Nat Neurosci. 2016 Dec;19(12):1628-1635. doi: 10.1038/nn.4392. Epub 2016 Sep 19. PMID: 27643429; PMCID: PMC5382799.
Mandelblat-Cerf Y, Ramesh RN, Burgess CR, Patella P, Yang Z, Lowell BB, Andermann ML. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. Elife. 2015 Jul 10;4:e07122. doi: 10.7554/eLife.07122. PMID: 26159614; PMCID: PMC4498165.
3. Synaptic plasticity in the excitatory inputs to AgRP hunger neurons.
RELEVANT PUBLICATIONS:
Grzelka K, Wilhelms H, Dodt S, Dreisow ML, Madara JC, Walker SJ, Wu C, Wang D, Lowell BB, Fenselau H. A synaptic amplifier of hunger for regaining body weight in the hypothalamus. Cell Metab. 2023 May 2;35(5):770-785.e5. doi: 10.1016/j.cmet.2023.03.002. Epub 2023 Mar 24. PMID: 36965483; PMCID: PMC10160008.
Kong D, Dagon Y, Campbell JN, Guo Y, Yang Z, Yi X, Aryal P, Wellenstein K, Kahn BB, Sabatini BL, Lowell BB. A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons. Neuron. 2016 Jul 6;91(1):25-33. doi: 10.1016/j.neuron.2016.05.025. Epub 2016 Jun 16. PMID: 27321921; PMCID: PMC4938763.
Liu T, Kong D, Shah BP, Ye C, Koda S, Saunders A, Ding JB, Yang Z, Sabatini BL, Lowell BB. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron. 2012 Feb 9;73(3):511-22. doi: 10.1016/j.neuron.2011.11.027. PMID: 22325203; PMCID: PMC3278709.
4. Highly-selective “labeled line-like” brain-to-gut communication by the parasympathetic nervous system.
RELEVANT PUBLICATION:
Tao J, Campbell JN, Tsai LT, Wu C, Liberles SD, Lowell BB. Highly selective brain-to-gut communication via genetically defined vagus neurons. Neuron. 2021 Jul 7;109(13):2106-2115.e4. doi: 10.1016/j.neuron.2021.05.004. Epub 2021 Jun 1. PMID: 34077742; PMCID: PMC8273126.
GENETIC METHODOLOGIES OF INTEREST:
A. Single neuron transcriptomics and spatial transcriptomics:
a) to establish the neuronal “parts-list” for key nodes in the hunger/satiety circuitry.
b) to identify the marker genes that are used for neuron subtype-specific recombinase mice.
This is done in collaboration with Linus Tsai and the BIDMC Division of Endocrinology Functional Genomics and Bioinformatics Core:
https://www.baderc.org/cores/functional-genomics-and-bioinformatics-core/
RELEVANT PUBLICATIONS:
The PVH: Resch J, Li Y, Butler T, Nardone S, Jacobs C, Douglass A, Madara J, McDonough M, Tao J, Lowenstein E, Wang L, Pant D, Walker S, Wang A, Srinivasan H, Yang Z, Campbell J, Tsai LT, Lowell B. A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types. Res Sq [Preprint]. 2025 Oct 21:rs.3.rs-7895391. doi: 10.21203/rs.3.rs-7895391/v1. PMID: 41282229; PMCID: PMC12633530.
The PBN/pLC: Nardone S, De Luca R, Zito A, Klymko N, Nicoloutsopoulos D, Amsalem O, Brannigan C, Resch JM, Jacobs CL, Pant D, Veregge M, Srinivasan H, Grippo RM, Yang Z, Zeidel ML, Andermann ML, Harris KD, Tsai LT, Arrigoni E, Verstegen AMJ, Saper CB, Lowell BB. A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution. Nat Commun. 2024 Mar 4;15(1):1966. doi: 10.1038/s41467-024-45907-7. PMID: 38438345; PMCID: PMC10912765.
The DMV (motor vagus): Tao J, Campbell JN, Tsai LT, Wu C, Liberles SD, Lowell BB. Highly selective brain-to-gut communication via genetically defined vagus neurons. Neuron. 2021 Jul 7;109(13):2106-2115.e4. doi: 10.1016/j.neuron.2021.05.004. Epub 2021 Jun 1. PMID: 34077742; PMCID: PMC8273126.
The Arcuate Nucleus: Campbell JN, Macosko EZ, Fenselau H, Pers TH, Lyubetskaya A, Tenen D, Goldman M, Verstegen AM, Resch JM, McCarroll SA, Rosen ED, Lowell BB, Tsai LT. A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci. 2017 Mar;20(3):484-496. doi: 10.1038/nn.4495. Epub 2017 Feb 6. PMID: 28166221; PMCID: PMC5323293.
B. Generation and use of neuron subtype-specific recombinase mice which enable neuron subtype-specific expression of “tools”.
Mice for Lowell Lab are generated by the BIDMC Transgenic Facility: https://research.bidmc.org/transgenic-core
Over 50 lines of mice have been generated by the Lowell Lab and shared with the research community: https://mice.jax.org/?searchTerm=Lowell
As of Dec., 2025, these mice have been featured in over 3,650 publications (as assessed using the Jackson Labs MGI-Mouse Genome Informatics Database).