|Neuroscience, neurobiology, epilepsy, epileptogenesis, learning and memory, stress, corticotropin releasing hormone, hippocampus, development, programming.|
2015: Elected member, American College of Neuropsychopharmacology
2013: Bernard Sachs Distinguished Award for Research, Child Neurology Society.
2011: Soriano Lectureship Award of the American Neurological Association.
2010: Mentorship Award; UCI Alumni Association.
2009: Distinguished Award for Research in Epilepsy, American Society of Pharmacology and Experimental Therapeutics.
2008: Distinguished Scholar Lectureship, Office of the President, University of California.
2006: National Institute of Health NINDS, Javits Merit award.
2005: Research Recognition Award in Basic Science, the premier Epilepsy Research honor.
2005-2010: Epilepsy Foundation, Research Council and Professional Advisory Board.
2004-2006: Elected, AES Executive Board
2003: American Epilepsy Society (AES) Research Initiative Award.
1999: Athalie Clarke Excellence in Research Award, University of California-Irvine.
1995-current: Danette D. Shepard Endowed Chair in Neurological Sciences, University of California-Irvine.
1991: American Epilepsy Society Young Investigator Research Award
1988-1993: NINDS: Career Development Research Award (KO8)
1978-1980: Kennedy Postdoctoral Award (highest Weizmann Institute Graduate Award)
1977: EMBO: Short-term International Research Award; In J. Axelrod’s lab, NIH, Bethesda
1976-1977: Bloom Fellowship for doctoral studies, life sciences, Weizmann Institute of Science
Tallie Z. Baram, MD, PhD is a Professor of Pediatrics, Anatomy/Neurobiology, Neurology and Physiology/Biophysics at the University of California-Irvine, and the Danette Shepard Professor of Neurological Sciences. Baram is a child neurologist and developmental neuroscientist and who has been focusing her efforts on programming the developing brain as a result of early-life experiences. Baram’s group has studied this broad topic in two contexts: a. how early-life experiences including stress and maternal care influence resilience and vulnerability to cognitive and emotional disorders; b. how early life seizures, especially those associated with fever, can convert a normal brain into an epileptic one. Using rodent models and cutting-edge molecular, cellular epigenetic and imaging methods, Baram’s group has made enormous contributions to our understanding of the effects of early-life experience on normal brain function and the contributions of early-life adversity and seizures to neuropsychiatric disorders. Baram’s discoveries have been translational, providing the foundation of an FDA-approved therapy and of novel clinical imaging approaches.
Baram’s research contributions have been recognized by prestigious awards including the NIH NINDS Javits Merit Award, AES Basic Science Research Award, and the CNS Sachs Award, and she has chaired the NIH Developmental Brain Disorders study section. Baram has had a long commitment to mentoring. She is PI of one of two NIH funded T32s focused on epilepsy, and is mentor of several currently funded K awards. Baram’s numerous students from diverse backgrounds are now contributing independently to Neuroscience research.
Research Description and Approach
We are interested in how early-life experience (specifically stress or seizures) influence the function of brain cells persistently ('re-program' them), to promote or protect from in human disease. We aim to understand the mechanisms of this neuroplasticity and employ the information to design therapies for prevention/treatment of stress-related disorders and epilepsy, respectively.
Lab members use molecular biology, transgenic, epigenetic and in vitro and in vivo imaging methods. We use both in animal models where genes are controlled in time and space and in vitro systems including slice cultures and dissociated neurons. We study:
(a) how seizures induce large-scale, epigenetic changes in gene transcription programs in neurons, and the mechanisms of this coordinate transformation of normal neurons into 'epileptic' ones.
(b) how early life stress or enriched experience modify gene expression and synaptic function in the hippocampus and in specific hypothalamic neurons, predisposing to- or protecting from-cognitive and emotional stress related disorders including depression. Students use genetically modified mice where hippocampal neurons are visible to examine in real time how stress and hormones influence dendritic spine dynamics and neuronal structure. They test how these changes influence learning and memory. Mechanisms of experience- induced changes in neuronal gene expression (programming) are studied using neuroanatomical, molecular biology and physiological approaches.
Lab members collaborate extensively, and publish in outstanding journals.
Selected peer-reviewed publications grouped by topic, in reverse chronology (of >192 peer reviewed):
NEUROBIOLOGY OF STRESS, LEARNING AND MEMORY AND THE CELLULAR MACHINERY OF CRH
Chen Y, Molet J, Lauterborn JC, Trieu BH, Bolton JL, Patterson KP, Gall CM, Lynch G, Baram TZ. Converging, synergistic actions of multiple stress hormones mediate enduring memory impairments after acute simultaneous stresses. J Neurosci, 2016.
Molet J, Maras PM, Kinney-Lang E, Harris NG, Rashid F, Ivy AS, Solodkin A, Obenaus A, Baram TZ. MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity. Hippocampus, 2016.
Obenaus A, Solodkin A, Dunn JF, Jullienne A, Baram TZ. Seeking the Amygdala: Novel use of Diffusion Tensor Imaging to Delineate the Basolateral Amygdala. PLOS ONE, 2016.
Molet J, Heins K, Zhuo X, Mei YT, Regev L, Baram TZ, Stern H. Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome. Transl Psychiatry, 6:e702, 2016.
Chen Y, Molet J, Gunn BG, Ressler K, Baram TZ. Diversity of reporter expression patterns in transgenic mouse lines targeting corticotropin releasing hormone-expressing neurons. Endocrinology, 156:4769-80, 2015.
Chen Y, Baram TZ. Towards Understanding How Early-Life Stress Re-Programs Cognitive and Emotional Brain Networks. Neuropsychopharmacology, 41:197-206, 2015.
Baglietto-Vargas D, Chen Y, Suh D, Ager RR, Rodriguez-Ortiz CJ, Medeiros R, Myczek K, Green KN, Baram TZ, LaFerla FM. Short-term modern life-like stress exacerbates Aß-pathology and synapse loss in 3xTg-AD mice. J Neurochem, 134:915-26, 2015.
Dubé CM, Molet J, Singh-Taylor A, Ivy A, Maras PM, Baram TZ. Hyper-excitability and epilepsy generated by chronic early-life stress. Neurobiol Stress, 2:10-19, 2015.
Singh-Taylor A, Korosi A, Molet J, Gunn BG, Baram TZ. Synaptic rewiring of stress-sensitive neurons by early-life experience: a mechanism for resilience? Neurobiol Stress, 1:109-115, 2015.
Molet J, Maras, PM, Avishai-Eliner S, Baram TZ. Naturalistic models of Chronic Early-Life Stress. Develop Psychobiol, 56:1675-88, 2014.
Maras PM, Chen Y, Molet J, Rice C, Ji SG, Solodkin A, Baram TZ. Preferential loss of dorsal-hippocampus synapses underlies memory process impairment provoked by short, multi-modal stress. Mol Psychiatry, 19:811-22, 2014.
Vogel-Ciernia A, Barrett RM, Matheos DP, Kramár E, Azzawi S, Chen Y, Magnan CN, Zeller M, Sylvain A, Haettig J, Jia Y, Tran A, Dang R, Post RJ, Chabrier M, Babayan A, Wu JI, Crabtree GR, Baldi P, Baram TZ, Lynch G, Wood MA. The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory. Nat Neurosci, 16:552-61, 2013.
Andres AL, Regev L, Phi L, Seese RR, Chen Y, Gall CM, Baram TZ. NMDA Receptor Activation and Calpain Contribute to Disruption of Dendritic Spines by the Stress Neuropeptide CRH. J Neurosci, 33:16945-60, 2013.
Chen Y, Kramár EA, Chen LY, Babayan AH, Andres AL, Gall CM, Lynch G, Baram TZ. Impairment of synaptic plasticity by the stress mediator CRH involves selective destruction of thin dendritic spines via RhoA signaling. Mol Psychiatry, 18:485-96, 2013.
Baram TZ, Davis EP, Obenaus A, Sandman CA, Small SL, Solodkin A, Stern H. Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders. Am J Psychiatry, 169:907-915, 2012.
Maras, PM, Baram TZ. Sculpting the Hippocampus from within: Stress, Spines, and CRH. Trends Neurosci, 35:315-24, 2012.
Ivy A, Rex C, Chen Y, Dubé C, Maras P, Grigoriadis D, Gall C, Lynch G, Baram TZ. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors. J Neurosci, 30:13005-13015, 2010.
Chen Y, Rex CS, Rice CJ, Dubé CM, Gall CM, Lynch G, Baram TZ. Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling. PNAS, 29:13123-13128, 2010.
Korosi A, Shanabrough M, McClelland S, Liu ZW, Borak E, Gao XB, Horvath TL, Baram TZ. Early-life experience reduces excitation to stress-responsive hypothalamic neurons and reprograms the expression of corticotropin-releasing hormone. J Neurosci, 30:703-713, 2010.
Joëls M, Baram TZ. The neuro-symphony of stress. Nature Reviews Neuroscience, 6:459-466, 2009.
Chen Y, Dubé C, Rice CJ, Baram TZ. Rapid loss of dendritic spines after stress involves derangement of spine dynamics by corticotropin-releasing hormone. J Neurosci, 28:2903-11, 2008.
Fenoglio KA, Brunson KL, Baram TZ. Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects. Front Neuroendocrinol, 27:180-92, 2006.
Chen Y, Fenoglio KA, Dubé CM, Grigoriadis DE, Baram TZ. Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent. Mol Psychiatry, 11:992-1002, 2006.
Brunson KL, Kramar E, Bin L, Chen Y, Colgin LL, Yanagihara TK, Lynch G, Baram TZ. Mechanisms of late onset cognitive decline after early life stress. J Neurosci, 25:9328-38, 2005.
Chen Y, Bender RA, Brunson KL, Pomper J, Grigoriadis DE, Wurst W, Baram TZ Modulation of dendritic differentiation by corticotropin releasing factor in the developing hippocampus. PNAS, 101:15782-15787, 2004.
Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ Stressed out? Or in (utero) Trends Neurosci, 25:518-524, 2002.
Roozendaal B, Brunson KL, Holloway B, McGaugh JL, Baram TZ. Involvement of stress-released Corticotropin-Releasing Hormone in the Basolateral Amygdala in Regulating Memory Consolidation. PNAS, 99:13908-13, 2002.
Brunson KL, Eghbal-Ahmadi M, Bender RA, Chen Y, BaramTZ. Long-term progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin releasing hormone reproduce the effects of early-life stress. PNAS, 98:8856-8861, 2001.
Brunson KL, Khan N, Eghbal-Ahmadi Baram TZ. Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression. Ann Neurol, 49:304-312, 2001.
Chen Y, Bender R, Frotscher M, Baram TZ. Novel and transient populations of corticotropin-releasing hormone-expressing neurons in developing hippocampus suggest unique functional roles: a quantitative spatiotemporal analysis. J Neurosci, 21:7171-7181, 2001.
Eghbal-Ahmadi M, Avishai-Eliner S, Hatalski CG, Baram TZ. Regulation of the expression of corticotropin releasing factor receptor type 2 (CRF2) in the hypothalamus and amygdala of the immature rat. J Neurosci, 19:3982-91, 1999.
Baram TZ, Hatalski CG Neuropeptide-mediated excitability: A key triggering mechanism for seizure generation in the developing brain. Trends Neurosci, 21:471-476, 1998.
EPILEPSY, SEIZURES, EPILEPTOGENESIS AND UNDERLYING MECHANISMS
Barry JM Sakkaki S, Barriere SJ, Patterson KP, Lenck-Santini P, Scott RC, Baram TZ, Holmes GL. Temporal Coordination of hippocampal neurons reflects cognitive outcome post-febrile status epilepticus. EBioMedicine, 7:175-190, 2016.
Brennan GP, Dey D, Chen Y, Patterson KP, Magnetta E, Hall AM, Dube CM, Mei Y-T, Baram TZ. Dual and opposing roles of microRNA-124 in the generation of epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Reports, 14:2402-12, 2016.
Patterson KP, Brennan GP, Curran M, Kinney-Lang E, Dubé C, Rashid F, Ly C, Obenaus A, Baram TZ. Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis. eNeuro, 2:e0034-15.2015, 2015.
Choy M, Dubé CM, Patterson K, Barnes SRS, Maras P, Blood AB, Hasso AN, Obenaus A, Baram TZ. A novel, noninvasive, predictive epilepsy biomarker with clinical potential. J Neurosci, 34:8672-84, 2014.
McClelland S, Brennan GP, Dubé C, Rajpara S, Iyer S, Richichi C, Bernard C, Baram TZ. The transcription factor NRSF: contributes to epileptogenesis by selective repression of a subset of target genes. eLife, 3:e01267, 2014.
Noam Y, Ehrengruber MU, Koh A, Feyen P, Manders EM, Abbott GW, Wadman WJ, Baram TZ. Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons. J Biol Chem, 289:5889-903, 2014.
Marcelin B, Liu Z, Chen Y, Lewis AS, Becker A, McClelland S, Chetkovich DM, Migliore M, Baram TZ, Esclapez M, Bernard C. Dorsoventral Differences in Intrinsic Properties in Developing CA1 Pyramidal Cells. J Neurosci, 32:3736-3747, 2012.
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol, 7:31-40, 2011.
McClelland S, Flynn C, Dubé C, Richichi C, Zha QQ, Ghestem A, Esclapez M, Bernard C Baram TZ Neuron-restrictive silencer factor-mediated hyperpolarization activated, cyclic nucleotide gated channelopathy in experimental temporal lobe epilepsy. Ann Neurol, 70:454-465, 2011.
Noam Y, Bernard C, Baram TZ. Towards an integrated view of HCN channel role in epilepsy. Curr Opin Neurobiol, 21:873-879, 2011.
Dubé CM, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci, 30:7484-7494, 2010.
Noam Y, Zha Q, Phan L, Wu RL, Chetkovich DM, Wadman WJ, Baram, TZ. Trafficking and surface expression of the hyperpolarization-activated nucleotide-gated (HCN) channels in hippocampal neurons. J Biol Chem, 285:14724-14736, 2010.
Lewis A, Schwartz E, Chan S, Noam Y, Shin M, Wadman W, Surmeier D, Baram TZ, Macdonald R, Chetkovich D. Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. J Neurosci, 19:6250-6265, 2009.
Dube C, Brewster AL, Richichi, C, Zha QQ, Baram TZ. Fever, febrile seizures and epilepsy. Trends Neurosci, 30:490-496, 2007.
Bender RA, Kirschstein T, Kretz O, Brewster AL, Richichi C, Rüschenschmidt C, Shigemoto R, Beck H, Frotscher M, Baram TZ. Localization of HCN1 channels to presynaptic compartments: novel plasticity that may contribute to hippocampal maturation. J Neurosci, 27:4697-4706, 2007.
Dubé C, Richichi C, Bender RA, Chung G, Litt B, Baram TZ. Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain, 129:911-22, 2006.
Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ. Interleukin 1? contributes to the generation of experimental febrile seizures. Ann Neurol, 57:152-155, 2005.
Dubé C, Yu H, Nalcioglu O, Baram TZ. Serial magnetic resonance imaging (MRI) after experimental febrile seizures: altered T2 signal does not signify neuronal death. Ann Neurol, 56:709-714, 2004.
Baram TZ. Long-term neuroplasticity and functional consequences of single versus recurrent early-life seizures. Ann Neurol, 54; 701-705, 2003.
Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ. Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus. J Neurosci, 23:6826-6836, 2003.
Santoro B, Baram TZ. The multiple personalities of the H Channels. Trends Neurosci, 26:550-554, 2003.
Sullivan PG, Dubé C, Dorenbos K, Steward O, Baram TZ. Mitochondrial uncoupling protein-2 contributes crucially to the resistance of immature brain to excitotoxic neuronal death. Ann Neurol, 53:711-717, 2003.
Brewster A, Bender RA, Chen Y, Eghbal-Ahmadi M, Dubé C, Baram TZ. Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform and cell-specific manner. J Neurosci, 22:4591-4599, 2002.
Chen K, Aradi I, Eghbal-Ahmadi M, Baram TZ, Soltesz I. Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition into hyperexcitability. Nature Medicine, 73:331-337, 2001.
Dubé C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long-term. Ann Neurol, 47:336-344, 2000.
Chen K, Baram TZ, Soltesz I. Febrile Seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nature Medicine, 5:888-894, 1999.
Toth Z, Yan XX, Heftoglu S, Ribak CE, Baram TZ. Seizure-induced neuronal injury: vulnerability to febrile seizures in an immature rat model. J Neurosci, 18:4285-4294, 1998.
Baram T, Koch Y, Hazum E, Fridkin M. Gonadotropin- releasing hormone in milk. Science, 198:300-302, 1977.
|Grants||NIH NIMH MH 96889 (P50, PI: Baram), 06/17/2013-04/30/2018, Fragmented early life environment and emotional/cognitive vulnerabilities.|
|NIH NINDS NS 35439 (R01, PI: Baram), 4/01/1997-07/31/2019, Epileptogenesis following FSE: mechanisms, biomarkers, prevention. (Senator Javits Career Merit award, R37; 2006-2014)|
|NIH NINDS NS 45540 (T32, PI: Baram), 7/01/2003 - 6/30/2019, Training grant for post-doctoral fellows focused on Epilepsy Research. (One of only two such grants in the U.S.)|
|NIH NIMH MH 73136 (R01, PI: Baram), 12/01/1999-05/31/2021, Effects of early life experience: Role of CRH.|
|NIH NINDS NS 78279 (R01, Multiple PIs: Gregory Holmes & Baram), 07/01/2011-06/30/2017, Cognitive deficits after experimental febrile seizures: neurobiology & biomarkers.|
|NIH PPG NS 45260 (P01, PI: Christine Gall, Project 4 PI: Baram), 09/01/2011-08/31/2016, BDNF and Spine-Related Disorders of Memory and Cognition.|
|Hewitt fellowship, Jessica Bolton, PhD (Sponsor: Baram), 10/01/2015-09/30/2018|
American College of Neuropsychopharmacology (elected)
American Neurological Association (elected)
International Society of Neuroendocrinology
American Epilepsy Society
Society for Neuroscience
American Association for Advancement of Science
American Academy of Neurology
Child Neurology Society
NIH NIMH Study Section for Conte Center Review
NIH CSR Special emphasis panel, BDCN R(02)
Chair, NIH NIMH P50 Conte Center Study Section
NIH CSR special emphasis panel, BDCN-N(02)
Interdepartmental Neuroscience Program
Cellular and Molecular Biosciences
|Research Centers||Epilepsy Research Center|
|Conte Center @ UCI|
|Center for Learning and Memory|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=4479|