Honors & Awards

  • T32 Postdoctoral Fellowship, National Institute of Mental Health (NIMH) (2018)
  • Martha Lucas Pate Award for Academic Excellence and Leadership, Board of Trustees, New York Medical College (2017)

Professional Education

  • Doctor of Philosophy, New York Medical College (2017)

All Publications

  • Pairing of neonatal phencyclidine exposure and acute adolescent stress in male rats as a novel developmental model of schizophrenia. Behavioural brain research Moghadam, A. A., Vose, L. R., Miry, O., Zhang, X., Stanton, P. K. 2021: 113308


    Improved understanding of the neurophysiological and neurochemical mechanisms underlying schizophrenia is essential for the identification of biological markers and developing new therapeutic targets. The development of behaviorally faithful, predictive animal models is crucial to this endeavor. We have developed a novel two-hit paradigm designed to recapitulate in rodents the developmental process leading to appearance of human schizophrenia symptomatology. The model pairs neonatal administration of the NMDA receptor (NMDAR) open-channel blocker phencyclidine (PCP 10mg/kg) to male rats at 7, 9 and 11 days of age, with later adolescent exposure (34 days of age) to a single prolonged stress paradigm consisting of 2h restraint, followed by 20minutes of forced swimming. Four experimental groups were examined: vehicle and no stress (VEH-NS), vehicle plus stress (VEH-S), PCP and no stress (PCP-NS), and PCP plus stress (PCP-S). Only pairing of neonatal PCP with single prolonged adolescent stress caused deficits in novel object recognition memory and increased anxiety-like behavior in the elevated plus maze task, without altering locomotor activity. In a separate cohort of animals, the PCP-S group showed significant reduction in magnitude of hippocampal long-term potentiation (LTP) at Schaffer collateral-CA1 synapses following a single pair of theta-burst stimuli (TBS), while LTP was diminished in both PCP treated groups when elicited by a second pair of TBS. These results suggest that the combination of neonatal PCP and acute adolescent stress are necessary for lasting cognitive impairment and anxiety-like phenotype, and that these behavioral impairments may be due to deficits in LTP in hippocampus, and perhaps elsewhere in the brain.

    View details for DOI 10.1016/j.bbr.2021.113308

    View details for PubMedID 33872663

  • Life-long brain compensatory responses to galactic cosmic radiation exposure. Scientific reports Miry, O., Zhang, X. L., Vose, L. R., Gopaul, K. R., Subah, G., Moncaster, J. A., Wojnarowicz, M. W., Fisher, A. M., Tagge, C. A., Goldstein, L. E., Stanton, P. K. 2021; 11 (1): 4292


    Galactic cosmic radiation (GCR) composed of high-energy, heavy particles (HZE) poses potentially serious hazards to long-duration crewed missions in deep space beyond earth's magnetosphere, including planned missions to Mars. Chronic effects of GCR exposure on brain structure and cognitive function are poorly understood, thereby limiting risk reduction and mitigation strategies to protect against sequelae from exposure during and after deep-space travel. Given the selective vulnerability of the hippocampus to neurotoxic insult and the importance of this brain region to learning and memory, we hypothesized that GCR-relevant HZE exposure may induce long-term alterations in adult hippocampal neurogenesis, synaptic plasticity, and hippocampal-dependent learning and memory. To test this hypothesis, we irradiated 3-month-old male and female mice with a single, whole-body dose of 10, 50, or 100 cGy 56Fe ions (600 MeV, 181 keV/μm) at Brookhaven National Laboratory. Our data reveal complex, dynamic, time-dependent effects of HZE exposure on the hippocampus. Two months post exposure, neurogenesis, synaptic plasticity and learning were impaired compared to sham-irradiated, age-matched controls. By six months post-exposure, deficits in spatial learning were absent in irradiated mice, and synaptic potentiation was enhanced. Enhanced performance in spatial learning and facilitation of synaptic plasticity in irradiated mice persisted 12 months post-exposure, concomitant with a dramatic rebound in adult-born neurons. Synaptic plasticity and spatial learning remained enhanced 20 months post-exposure, indicating a life-long influence on plasticity and cognition from a single exposure to HZE in young adulthood. These findings suggest that GCR-exposure can persistently alter brain health and cognitive function during and after long-duration travel in deep space.

    View details for DOI 10.1038/s41598-021-83447-y

    View details for PubMedID 33619310

    View details for PubMedCentralID PMC7900210

  • The Quest for the Hippocampal Memory Engram: From Theories to Experimental Evidence. Frontiers in behavioral neuroscience Miry, O., Li, J., Chen, L. 2020; 14: 632019


    More than a century after Richard Semon's theoretical proposal of the memory engram, technological advancements have finally enabled experimental access to engram cells and their functional contents. In this review, we summarize theories and their experimental support regarding hippocampal memory engram formation and function. Specifically, we discuss recent advances in the engram field which help to reconcile two main theories for how the hippocampus supports memory formation: The Memory Indexing and Cognitive Map theories. We also highlight the latest evidence for engram allocation mechanisms through which memories can be linked or separately encoded. Finally, we identify unanswered questions for future investigations, through which a more comprehensive understanding of memory formation and retrieval may be achieved.

    View details for DOI 10.3389/fnbeh.2020.632019

    View details for PubMedID 33519396

  • Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain : a journal of neurology Tagge, C. A., Fisher, A. M., Minaeva, O. V., Gaudreau-Balderrama, A., Moncaster, J. A., Zhang, X. L., Wojnarowicz, M. W., Casey, N., Lu, H., Kokiko-Cochran, O. N., Saman, S., Ericsson, M., Onos, K. D., Veksler, R., Senatorov, V. V., Kondo, A., Zhou, X. Z., Miry, O., Vose, L. R., Gopaul, K. R., Upreti, C., Nowinski, C. J., Cantu, R. C., Alvarez, V. E., Hildebrandt, A. M., Franz, E. S., Konrad, J., Hamilton, J. A., Hua, N., Tripodis, Y., Anderson, A. T., Howell, G. R., Kaufer, D., Hall, G. F., Lu, K. P., Ransohoff, R. M., Cleveland, R. O., Kowall, N. W., Stein, T. D., Lamb, B. T., Huber, B. R., Moss, W. C., Friedman, A., Stanton, P. K., McKee, A. C., Goldstein, L. E. 2018; 141 (2): 422-458


    The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.

    View details for DOI 10.1093/brain/awx350

    View details for PubMedID 29360998

    View details for PubMedCentralID PMC5837414

  • From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children. Toxicological sciences : an official journal of the Society of Toxicology Zhang, X. L., McGlothan, J. L., Miry, O., Stansfield, K. H., Loth, M. K., Stanton, P. K., Guilarte, T. R. 2018; 161 (1): 186-195


    Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children.

    View details for DOI 10.1093/toxsci/kfx210

    View details for PubMedID 29029315

    View details for PubMedCentralID PMC5837521