Michael Cahill

mcahill4@wisc.edu

Department of Comparative Biosciences
Office: 3462

Michael Cahill

Titles and Education

  1. B.A. in Neuroscience and Psychology, Lawrence University, Appleton, WI, 2001
  2. Ph.D. in Neuroscience, Northwestern University, Evanston & Chicago, IL, 2011
  3. Postdoctoral Fellow in Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 2011-2017

Research

Dendritic spines are the sites of most excitatory connections in the central nervous system. The central goal of my laboratory is to delineate the molecular and biochemical mechanisms that regulate dendritic spine plasticity in both the normal and diseased brain. In particular, using animal models, I am interested in recapitulating the genetic and biochemical alterations identified in neuropsychiatric disorders to identify brain region-specific aberrations in dendritic spine formation, stability, and experience-dependent remodeling. I then aim to understand how these regional synaptic changes, in turn, contribute to specific disease-associated behavioral phenotypes. Finally, I am interested in understanding how environmental-based risk factors for neuropsychiatric disease interact with specific genetic susceptibility factors to produce synaptic and behavioral phenotypes.

One approach used by my lab is in vivo viral-mediated gene transfer in which the expression of a gene and associated protein product are manipulated in an individual brain region. Further, within individual brain regions, viral-mediated gene transfer can enable the genetic manipulation of specific neuronal subtypes and specific neuronal populations. Viral approaches have the advantage of directly linking the altered expression/activity of neuropsychiatric disease-associated proteins in a single brain region with specific behavioral endophenotypes. This helps clarify the role of altered dendritic spine morphogenesis in individual brain structures in mediating disease-associated behavioral dysfunction.

While the study of individual brain regions helps demystify the critical structures regulating specific behaviors, complex behaviors are invariably the product of dynamic regulations in the functional connectivity between multiple brain regions. Altered structural and functional connections between brain regions, both proximal and distal, are commonly associated with neuropsychiatric disorders. However, the consequences of these alterations on neuronal structure and behavior are seldom known. Using in vivo circuit-based manipulations (e.g., optogenetics and DREADDs), my laboratory aims to understand how altered interbrain region connectivity patterns identified in neuropsychiatric diseases impact dendritic spine formation, maturation, and stability, and the consequent effects on behavioral functioning.

Using the approaches described above, my laboratory seeks to understand how altered structural and functional plasticity in brain reward circuits potentially give rise to the social motivational impairments characteristic of autism spectrum disorders. In addition, my laboratory aims to better understand the etiology of executive processing (e.g., working memory) dysfunction in schizophrenia by the investigation of specific prefrontal cortical circuits.

Responsibilities

Veterinary Neuroanatomy-Neurophysiology (spring semester)

Graduate Training

Neuroscience Training Program

Graduate Program in Cellular and Molecular Biology

Recent Publications

  1. Cahill ME, Walker DM, Gancarz AM, Wang ZJ, Lardner CK, Bagot RC, Neve RL, Dietz DM, Nestler EJ. The dendritic spine morphogenic effects of repeated cocaine use occur through the regulation of serum response factor (SRF) signaling. Molecular Psychiatry (2017) (in press)
  2. Labonté B, Engmann O, Purushothaman I, Menard C, Wang J, Tan C, Scarpa JR, Moy G, Loh YE, Cahill M, Lorsch ZS, Hamilton PJ, Calipari ES, Hodes GE, Issler O, Kronman H, Pfau M, Obradovic ALJ, Dong Y, Neve RL, Russo S, Kazarskis A, Tamminga C, Mechawar N, Turecki G, Zhang B, Shen L, Nestler EJ. Sex-specific transcriptional signatures in human depression. Nature Medicine (2017) 23(9) 1102-1111.

  3. Ceglia I, Lee KW, Cahill ME, Graves SM, Dietz D, Surmeier DJ, Nestler EJ, Nairn AC, Greengard P, Kim Y. WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine.  Proceedings of the National Academy of the Sciences (2017) 114 (6): 1395-1400.
  4. Calipari ES, Juarez B, Morel C, Walker DM, Cahill ME, Ribeiro E, Roman-Ortiz C, Ramakrishnan C, Deisseroth K, Han MH, Nestler EJ. Dopaminergic dynamics underlying sex-specific cocaine reward.  Nature Communications (2017) 8: 13877.
  5. Damez-Werno D, Sun H, Socobe KN, Shao N, Rabkin J, Dias C, Calipari ES, Maze I, Pena CJ, Walker DM, Cahill ME, Chandra R, Gancarz A, Mouzon E, Landry JA, Cates H, Lobo MK, Dietz D, Allis CD, Guccione E, Turecki G, Defilippi P, Neve RL, Hurd YL, Shen L, Nestler EJ. Histone arginine methylation in cocaine action in the nucleus accumbens.  Proceedings of the National Academy of the Sciences (2016) 113 (34): 9623-9628.
  6. Cahill ME, Bagot RC, Gancarz AM, Walker DM, Sun H, Wang Z, Heller EA, Feng J, Kennedy PJ, Koo JW, Cates HM, Neve RL, Shen L, Dietz DM, Nestler EJ.  Bidirectional synaptic structural plasticity after chronic cocaine administration occurs through Rap1 small GTPase signaling.  Neuron (2016) 89: 566-582.
  7. Heshmati M, Golden SA, Pfau ML, Christoffel DJ, Seeley EL, Cahill ME, Khibnik LA, Russo SJ. Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice.  Neuropharmacology (2015) 101: 351-357.
  8. Sun H, Damez-Werno DM, Scobie KN, Shao N, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonté B, Mouzon E, Heller EA, Cate H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ.  ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.  Nature Medicine (2015) 21: 1146-1153.
  9. Feng J, Shao N, Szulwach K, Vialou V, Huynh J, Zhone C, Le T, Ferguson D, Cahill ME, Li Y, Koo JW, Ribeiro E, Labonte B, Laitman B, Estey D, Stockman V, Kennedy P, Courousse T, Mensah I, Turecki G, Faull K, Song H, Fan G, Casaccia P, Shen L, Jin P, Nestler EJ.  Role of Tet1 and 5-hydroxymethylcytosine in cocaine action.  Nature Neuroscience (2015) 18: 536-544.
  10. Koo JW, Mazei-Robison M, LaPlant Q, Egervari G, Braunscheidel K, Adank D, Ferguson D, Feng J, Sun H, Scobie K, Damez-Werno D. Riberio E, Pena C, Walker D, Bagot R, Cahill ME, Anderson SA, Labonte B, Hodes G, Browne H, Chadwick B, Robison A, Vialou V, Dias C, Lorsch Z, Mouzon E, Lobo MK, Dietz D, Russo S, Neve R., Hurd Y, Nestler EJ.  Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area.  Nature Neuroscience (2015) 18: 415-422.
  11. Russell TA, Blizinsky KD, Cobia DJ, Cahill ME, Xie Z, Sweet RA, Duan J, Gejman PV, Wang L, Csernansky JG, Penzes P.  A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness.  Nature Communications (2014) 5: 4858.
  12. Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo J, Dias C, Laitman B, Stockman V, Laplant Q, Cahill ME, Nestler EJ, Shen L.  Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.  Genome Biology (2014) 15: R65.
  13. Vialou V, Bagot RC, Cahill ME, Ferguson D, Robison AJ, Dietz DM, Fallon B, Mazei-Robison M, Ku SM, Harrigan E, Winstanley CA, Joshi T, Feng J, Berton O, Nestler EJ.  Prefrontal Cortical Circuit for Depression- and Anxiety-Related Behaviors Mediated by Cholecystokinin: Role of ΔFosB.  Journal of Neuroscience (2014) 34: 3878-3887.
  14. Penzes P, Remmers C, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM. Structural alterations of synapses in psychiatric and neurodegenerative disorders. The Synapse: Strucutre and Function. Academic Press (2014). 281-300.
  15. Wang X, Cahill ME, Werner CT, Christoffel DJ, Golden SA, Xie Z, Loweth JA, Marinelli M, Russo SJ, Penzes P, Wolf ME. Kalirin-7 mediates cocaine-induced AMPA receptor and spine plasticity, enabling incentive sensitization.  Journal of Neuroscience (2013) 33: 11012-11022.
  16. Cahill ME, Reemers C, Jones KA, Xie Z, Sweet RA, Penzes P.  Neuregulin1 signaling promotes dendritic spine growth through kalirin.  Journal of Neurochemistry (2013) 126: 625-635.
  17. Golden SA, Christoffel DJ, Heshmati M, Hodes GE, Magida J, Davis K, Cahill ME, Dias C, Ribeiro E, Ables JL, Kennedy PJ, Robison AJ, Gonzalez-Maeso J, Neve RL, Turecki G, Ghose S, Tamminga CA, Russo SJ.  Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression.  Nature Medicine (2013) 19: 337-344.
  18. Srivastava DP, Copits BA, Xie Z, Huda R, Jones KA, Mukherji S, Cahill ME, Vanleeuwen JE, Woolfrey KM, Rafalovich I, Swanson GT, Penzes P.  Afadin is required for maintenance of dendritic structure and excitatory tone.  Journal of Biological Chemistry (2012) 287: 35964-35974. 
  19. Dietz DM, Sun H, Lobo MK, Cahill ME, Chadwick B, Gao V, Koo JW, Mazei-Robison MS, Dias C, Maze I, Damez-Werno D, Dietz KC, Scobie KN, Ferguson D, Christoffel D, Ohnishi Y, Hodes GE, Zheng Y, Neve RL, Hahn KM, Russo SJ, Nestler EJ.  Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons.  Nature Neuroscience (2012) 15: 891-896.
  20. Nicholson DA, Cahill ME, Tulisiak CT, Geinisman Y, Penzes P.  Spatially restricted actin-regulatory signaling contributes to synapse morphology.  Journal of Neurochemistry (2012) 121: 852-860.
  21. Penzes P, Cahill ME.  Deconstructing the signal transduction pathways the regulate the actin cytoskeleton in dendritic spines.  Cytoskeleton (2012) 69: 426-441.
  22. Deo AJ, Cahill ME, Li S, Goldszer I, Henteleff R., VanLeeuwen JE, Rafalovich I, Gao R, Stachowski EK, Sampson AR, Lewis DA, Penzes P, Sweet RA. Increased expression of kalirin-9 in the auditory cortex of schizophrenia subjects: its role in dendritic pathology.  Neurobiology of Disease (2012)  45: 796-803.
  23. Cahill ME, Jones KA, Rafalovich I, Xie Z, Barros CS, Müller U, Penzes P.  Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition.  Molecular Psychiatry (2012)  17: 99-107.
  24. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM.  Dendritic spine pathology in neuropsychiatric disorders.  Nature Neuroscience (2011) 14: 285-293.
  25. Xie Z, Cahill ME, Radulovic J, Wang J, Campbell SL, Miller CA, Sweatt JD, Penzes P.  Hippocampal phenotypes in kalirin-deficient mice.  Molecular and Cellular Neuroscience (2011) 46: 45-54.
  26. Cahill ME, Xie Z, Day M, Barbolina MV, Photowala H, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ, Penzes P. Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes.  Proceedings of the National Academy of the Sciences (2009) 106: 13058-13063.
  27. Xie Z, Cahill ME, Penzes P.  Kalirin loss results in cortical morphological alterations.  Molecular and Cellular Neuroscience (2009) 43: 81-89.
  28. Woolfrey KM, Srivastava DP, Photowala H, Yamashita M, Barbolina MV, Cahill ME, Xie Z, Jones KA, Quilliam LA, Prakriya M, Penzes P. Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines.  Nature Neuroscience (2009) 12: 1275-1284.
  29. Penzes P, Cahill ME, Jones KA, Srivastava DP. Convergent CaMK and RacGEF signals control dendritic structure and function.  Trends in Cell Biology (2008) 18: 405-413.
  30. Xie Z, Photowala H, Cahill ME, Srivastava DP, Woolfrey KM, Shum CY, Huganir RL, Penzes P. Coordination of synaptic adhesion with dendritic spine remodeling by AF-6 and kalirin-7.  Journal of Neuroscience (2008) 28: 6079-6091.
  31. Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM, Shum CY, Surmeier DJ, Penzes P.  Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines.  Neuron (2007) 56: 640-656.
  32. Guillozet-Bongaarts AL, Glajch KE, Libson EG, Cahill ME, Bigio E, Berry RW, Binder LI.  Phosphorylation and cleavage of tau in non-AD tauopathies.  Acta Neuropathologica (2007) 113: 513-520.
  33. Guillozet-Bongaarts AL, Cahill ME, Cryns VL, Reynolds MR, Berry RW, Binder LI.  Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo.  Journal of Neurochemistry (2006) 97: 1005-1014.
  34. Guillozet-Bongaarts AL, Garcia-Sierra F, Reynolds MR, Horowitz PM, Fu Y, Wang T, Cahill ME, Bigio EH, Berry RW, Binder LI.  Tau truncation during neurofibrillary tangle evolution in Alzheimer’s disease.  Neurobiology of Aging (2005) 26: 1015-1022.
  35. Vaquero J, Chung C, Cahill ME, Blei AT.  Pathogenesis of hepatic encephalopathy in acute liver failure.  Seminars in Liver Disease (2003) 23: 259-269.