Anatomy & Neurobiology
Physiology & Biophysics
Working to understand: (1) Mechanisms by which early life experience, including chronic stress influences adult learning and memory. (2) Mechanisms by which early-life enriched sensory input enhances cognitive and emotional outcomes. (3) Mechanisms by which the normal brain becomes epileptic.
Scientific Focus: Stress, epilepsy, development, "programming", gene expression, epigenetics, plasticity, learning/memory, depression, imaging, molecular biology.
Methods: (1) Transgenic and viral-mediated control of gene expression in time and space. (2) In vitro organotypic slice cultures(hippocampus, hypothalamus). (3) Live multiphoton imaging of spine and synapse dynamics. (4) In vivo, high-field rodent MR imaging, including DTI, fMRI. (5) Epigenetics: chromatin immunoprecipitation (ChIP), ChIP seq, RNA seq, gene network analyses, informatics. (6) Molecular: rtPCR, ISH, Co-IP, pulldowns, pharmacological pathway dissection. (7) Cognitive and emotional behavioral tasks.
Choy M, Dubé CM, Patterson K, Barnes SRS, Maras P, Blood AB, Hasso AN, Obenaus A, Baram TZ. A novel, non-invasive, predictive epilepsy biomarker with clinical potential. J Neurosci, 35:8672-84, 2014.
McClelland S, Brennan GP, Dube 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.
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, RichichiC, ZhaQQ, 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, 70:454-65, 2011.
Noam Y, Bernard C, Baram TZ. Towards an integrated view of HCN channel role in epilepsy. Curr Opin Neurobiol, 21:873-79, 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, 30:7484-94, 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 channels in hippocampal neurons J Biol Chem, 285:14724-36, 2010.
Richichi C, Brewster AL, Bender RA, Simeone TA, Zha Q, Yin HZ, Weiss JH, Baram TZ. Mechanisms of seizure-induced 'transcriptional channelopathy' of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Neurobiol Dis, 29:297-305, 2008.
Dube C, Brewster AL, Richichi, C, Zha QQ, Baram TZ. Fever, febrile seizures and epilepsy. Trends Neurosci, 30:490-96, 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, 27:4697-706, 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, 57:152-55, 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, 56:709-14, 2004.
Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ. Enhanced expression of specific HCN in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus. J Neurosci, 23:6826-36, 2003.
Santoro B, Baram TZ. The multiple personalities of the H Channels. Trends Neurosci, 26:550-54, 2003.
Brewster A, Bender RA, Chen Y, Eghbal-Ahmadi M, Dubé C, Baram TZ. Developmental febrile seizures modulate hippocampal gene expression of HCN channels in an isoform and cell-specific manner. J Neurosci, 22:4591-99, 2002.
Chen K, Aradi I, Eghbal-Ahmadi M, Baram TZ, Soltesz I. Persistently modified h-channels after complex febrile seizures convert seizure-induced enhancement of inhibition into hyperexcitability. Nature Medicine,73:331-77, 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, 47:336-44, 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, 5:888-94, 1999.
Baram TZ, Hatalski CG. Neuropeptide-mediated excitability: a key triggering mechanism for seizure generation in the developing brain. Trends Neurosci, 21:471-76, 1998.
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, 18:4285-94, 1998.
Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics, 97:375-9, 1996.
Maras PM, Molet J, Chen Y, Rice C, Ji SG, Solodkin A, Baram TZ. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress. Mol Psychiatry, 19:811-22, 2014. (IF = 15)
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.
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.
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, 169:907-15, 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 activation of CRH receptors. J Neurosci,30:13005-15, 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, 29:13123-28, 2010.
Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ. Early-life experience reduces excitation to stress-responsive hypothalamic neurons and re-programs the expression of corticotropin releasing hormone. J Neurosci, 30:703-13, 2010.
Joëls M, Baram TZ. The Neuro-symphony of Stress. Nature Reviews Neuroscience, 10:459-66, 2009. (IF = 34)
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, Chen Y, Baram TZ. Neuroplasticity of the hypothalamic-pituitary-adrenal (HPA) axis early in life requires recurrent recruitment of stress-regulating brain regions. J Neurosci, 26:2434-42, 2006.
Chen Y, Fenoglio KA, Dube 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, Kramár E, Lin B, Chen Y, Colgin LL, Yanagihara TL, 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 developing hippocampus. PNAS, 101:15782-87, 2004.
Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ. ‘Stressed out?’ Or in (utero). Trends Neurosci, 25:518-24, 2002.
Roozendaal B, Brunson KL, Holloway B, McGaugh JL, Baram TZ. Involvement of stress-released CRH in the basolateral amygdala in regulating memory consolidation. PNAS, 99:13908-13, 2002.
Brunson KL, Eghbal-Ahmadi M, Roland R, Chen Y, Baram TZ. Long-term progressive hippocampal cell loss and dysfunction induced by early-life stress. PNAS, 98:8856-61, 2001.
Brunson KL, Khan N, Eghbal-Ahmadi, Baram TZ. ACTH acts directly on amygdala neurons to down-regulate corticotropin releasing hormone gene expression. Ann Neurol, 49:304-13, 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, 21:7171-81, 2001.
Eghbal-Ahmadi M, Avishai-Eliner S, Hatalski CG, Baram TZ. Differential regulation of the expression of corticotropin releasing factor receptor type 2 (CRF2) in hypothalamus and amygdala of the immature rat by sensory input and food intake. 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, 21:471-76, 1998.
Baram T, Koch Y, Hazum E, Fridkin M. Gn-RH in milk. Science, 198:300-02, 1977.
Febrile Seizures. Baram TZ & Shinnar S, Eds. Academic Press, 2002.
NIH NIMH P50 MH 096889 (Conte center; PI: Baram) 06/17/2013 - 04/30/2018
Fragmented early life environment and emotional / cognitive vulnerabilities
NIH NINDS, R01 NS35439, (PI: Baram) (Javits merit award renewed as RO1) 04/01/1997 – 07/31/2019
Epileptogenesis following FSE: mechanisms, biomarkers, prevention
NIH NINDS R01 NS 28912 (PI: Baram) 03/01/1992 - 06/30/2015
CRH in stress-induced hippocampus neuroplasticity
NIH NIMH R01 MH 73136 (PI: Baram) 12/01/1999 - 02/28/2015
Effects of Early-life experience: Role of CRH
NIH/NINDS R01 NS078279 (MPIs: Holmes & Baram) 09/30/2011 - 06/30/2016
Cognitive deficits after experimental febrile seizures; neurobiology and biomarkers
NIH NINDS P20 NS 80185 (PI: McNamara, Baram, investigator) 09/20/2012 – 06/30/2015
Prevention of Temporal Lobe Epilepsy
NIH NINDS P01 NS 45260 (Gall CM, PI, Baram, Project 4) 10/01/2011 - 08/31/2016
BDNF and Spine-Related Disorders of Memory and Cognition
NIH NINDS T32 NS 45540: (Baram, PI) 07/01/2003 - 06/30/2019
Training grant for post-doctoral fellows focused on Epilepsy Research
Devin Binder, MD, PhD: K08. D. Bota, MD, PhD: K08. Jack Lin, MD: K23. Autumn Ivy, MSTP student: F30.
Katelin Patterson, EFA Predoctoral award; Gary Brennan, PhD, Hewitt Postdoctoral fellowship.
B151, C237 Med Sci I,
University of California
Irvine, California 92697-4475
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