Current Topics of Research in the Lab Include 

a) How early-life adversity/stress provokes anhedonia, and the underlying perturbations of the maturation of reward/pleasure circuitry.

b) How early-life adversity/stress provokes spatial memory deficits and the transcriptional / epigenomic mechanisms that re-program hippocampal neurons and circuits

c) How prolonged early-life seizures, especially those associated with fever, disrupt the maturation of hippocampal circuits and memory processes

d) Intra-individual methylomics in rodents and humans as predictive biomarkers of early-life adversity-induced cognitive and emotional problems

e) How multiple concurrent acute stresses, such as occur in mass shootings and natural disasters, impact memory processes in males and females.

Tallie Z. Baram

Tallie Z. Baram, MD, PhD is the Danette Shepard, Bren and distinguished professor at UCI School of Medicine. She is a developmental neuroscientist and child neurologist who has focused her research efforts on the influence of early-life experiences on brain maturation and the underlying mechanisms. Throughout her career, Baram has studied this topic in two broad contexts, pertaining, respectively, to stress-related and activity-dependent plasticity: a) How early-life experiences including adversity/stress promote enduring vulnerability to cognitive and emotional disorders; and b) how early-life seizures, especially those associated with fever, can convert a normal brain into an epileptic one.

A common thread of Baram’s research program is the use of multiple and trans-disciplinary technologies and levels of analysis including molecular, cellular and circuit methods and cross-species studies. She employed these to uncover how adverse early-life experiences sculpt memory-, stress- and reward-related circuit maturation. In this context, she has uncovered novel types of adversity in humans and rodents (unpredictable sequences of sensory signals) that contributes to aberrant circuit maturation (e.g., Birnie & Baram, Science, 2022). Additionally, she has focused on the overarching hypothesis that neuronal populations and projections expressing the stress-related peptide CRH may be particularly vulnerable to early-life adversity, resulting in disrupted operations of networks that include them. This notion has led to identification of novel CRH+ reward-circuit projections, and assessments of established CRH-cell populations using single-cell transcriptomics.

The Baram lab has pioneered naturalistic, translationally-relevant paradigms of early-life adversity (ELA) that have been embraced world-wide, and demonstrated the causal influence of ELA on cognitive and emotional health via convergent actions of multiple mediators (including locally-synthesized CRH). More recently, through collaborative work in her NIH funded Conte Center and a recent collaborative award with CHOC from the California Initiative to Advance Precision Medicine, she is translating her discoveries back to the clinic. Her work has been published in leading journals (e.g., Science, Nature Rev Neurosci, Nature Medicine, Nature Neurosci) and cited over 30,000 times (H = 96, google scholar). Baram’s discoveries have been universally recognized, apparent from awards including the NIH NINDS Javits Merit Award, premier Research Awards of the AES (2005), CNS (2013), ANA (2014) and AAN (2018), and a Public Impact Award (CNLM, 2022). 

Baram strives to contribute to the scientific community by, for examples, chairing NIH study sections and involvement in editorial boards and professional organizations, including ACNP. She is passionate and committed to mentoring, with emphasis on scientific rigor and inclusivity: Baram is PI of one of only two NIH-funded T32s focused on Epilepsy, and mentor of several recent K99 and F30 awardees. Many of her trainees, from diverse racial and geographical backgrounds are now contributing independently and successfully to our understanding of the brain in health and disease.

Lab News: 

DECEMBER 2025 | Congratulations to Lara for being awarded the Dr. Lorna Carlin Scholar Award!

Congratulations to Samantha & Izza for being awarded the UROP Research Experience Fellowship for their project “Investigating the Effect of Estrogen and Stress on Age-related Memory Loss” under the supervision of Rachael and Dr. Baram!

In this preprint, Dr. Baram & collaborators examined, in mice, the effects of a limited bedding and nesting (LBN) model of Early life stress on pup ultrasonic vocalizations (USVs). During adolescence they assessed social behavior as well as thymus involution and adrenal hypertrophy, both biomarkers of stress. They found reductions in USVs and adolescent mice had smaller thymus and adrenal glands with some mice produced signs of precocious puberty in both sexes, especially those in cohorts of LBN-exposed offspring bred to create second-generation LBN offspring. Together, these data suggest that stress in early life has distinct and diverse effects, including accelerating several processes, and that some of these effects persist intergenerationally. This preprint is available in bioRxiv: Early life stress induces social behavioral deficits and peripheral biomarker alterations in adolescence that perpetuate intergenerationally (link to preprint).

NOVEMBER 2025 | Lara, Dr. Chen, Matt, Anamika & Amanda probe the sex-specific role of the CRH/GABA BLA-NAc projection in reward behaviors. Chemogenetic manipulations in adult male mice demonstrated inhibitory effects of the projection on reward behaviors, whereas neither excitation nor inhibition influenced female behaviors. Molecular and electrophysiological cell-identities of the projection did not vary by sex. By contrast, whole-brain mapping uncovered significant differences in NAc innervation patterns that were both sex and ELA-dependent, as well as selective changes of innervation of other brain regions. This paper is available in J Neurosci: Sex and stress govern the function and innervation of a basolateral amygdala to nucleus accumbens corticotropin releasing hormone/GABA expressing projection (link to paper).

OCTOBER 2025 | Congratulations to Lara on receiving the Stanley Behrens Health Sciences Research Award!

Congratulations to Isabelle for being awarded Excellence in Research and a UROP fellowship for her project “How Early Life Adversity Shapes Motivation and Brain Function” under the supervision of Mason and Dr. Baram!

In this publication, co-first authors Madi and Bianca address discrepancies in the location and extent of the human PVT utilizing high-power MRI and histological studies of a post-mortem human brain. They found that the human PVT includes more posterior area than previously appreciated by MRI studies, but that this has minimal impact on functional connectivity. The increased posterior area of the human PVT introduces important opportunities to examine the posterior in human behavioral fMRI paradigms. This paper is available in Hum Brain Mapp: A combined neuroantaomy, ex vivo imaging and immunohistochemistry defined MRI mask for the human paraventricular nucleus of the thalamus (link to paper).

SEPTEMBER 2025 | In this collaboration, Ryan and Amalia discuss the potential molecular mechanisms through which early life adversity (ELA) changes the brain enduringly, with implications for mental health in adulthood. First, they discuss human and animal studies that focus on ELA-induced changes in the brain’s gene expression programs. Next, they explore recent technological advances that allow permanent genetic access to neurons that were activated during ELA. Specifically, they discuss how Targeted Recombination in Active Populations (TRAP) is used to discover, manipulate and study brain areas that might encode the ELA experience. Coupled with the appropriate tools, TRAP can help identify transcriptional programs in specific cells and circuits that might directly contribute to the long-lasting effects of ELA. This paper is available in Front Neurosci: Probing the roles of developmentally active neurons, in early-life adversity induced disruptions of adult behaviors (link to paper).

AUGUST 2025 | Congratulations to Mason on his Advancement!

In this recent pre-print, co-first authors Madi and Bianca address discrepancies in the location and extent of the human PVT utilizing high-power MRI and histological studies of a post-mortem human brain. They found that the human PVT includes more posterior area than previously appreciated by MRI studies, but that this has minimal impact on functional connectivity. The increased posterior area of the human PVT introduces important opportunities to examine the posterior in human behavioral fMRI paradigms. This paper is available in bioRxiv: A combined neuroantaomy, ex vivo imaging and immunohistochemistry defined MRI mask for the human paraventricular nucleus of the thalamus (link to paper).

JULY 2025 | In this collaboration, early-life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC) and participants engaged in 1 or more task-fMRI scans. Exposure to early-life unpredictability was associated with BOLD contrast (novel vs. familiar) in a sex-specific manner. For boys, but not girls, higher QUIC scores were associated with lower BOLD activation in response to novel versus familiar stimuli in the hippocampal head and amygdala. Furthermore, impacts of early-life unpredictability were independent of other risk factors. This paper is available in Biol Psychiatry Glob Open Sci: Sex-specific effects of early-life unpredictability on hippocampal and amygdala responses to novelty in adolescents (link to paper).

MAY 2025 | Congratulations to Brinda for being awarded 1st place for her UROP poster and on being named a Finalist on her Excellence in Research project “Testing the role of estrogen receptors in hippocampus-dependent memory using inducible male and female estrogen receptor knockout mice”, under the supervision of Rachael and Dr. Baram!

MARCH 2025 | Congratulations to Rachael on receiving the CNLM Director’s Excellence Award!

Congratulations to Lara on receiving the Norman M. Weinberger Award!

Rachael, Dr. Chen, Annabel & Brinda found that high physiological hippocampal estrogen levels were required for ATS-induced episodic memory disruption and the concurrent sensitization and generalization of fear memories in both male and female mice. Pharmacological and transgenic approaches demonstrated signaling via estrogen reception (ER)α in males and, in contrast, ERβ in females, as the mechanisms for these memory problems. This paper is available in bioRxiv: Unexpected mechanisms of sex-specific memory vulnerabilities to acute traumatic stress (link to paper).

FEBRUARY 2025 | In this collaboration, researchers found that combining screening with the QUIC-5 and an adverse early life experiences (ACEs) measure in the real-world setting significantly improved prediction of child health outcomes. For both screeners, increasing exposures were associated with a high probability of mental or physical health diagnosis. Across most diagnoses, PEARLS and QUIC provided unique predictive contributions. Importantly, for three outcomes (depression, obesity, sleep disorders) QUIC-5 identified vulnerable individuals that were missed by PEARLs alone. This paper is available in medRxiv: Contribution of an under-recognized adversity to child health risk: large-scale, population-based ACEs screening (link to paper).