Education

B.S. Neuroscience - College of William and Mary

Ph.D. Neuroscience - Wake Forest University

Post Doctoral Fellowship in Age-Related Memory Loss - University of Florida

Research

Research Focus:

The unifying goal of research in our laboratory is to elucidate fundamental processes affiliated with neural aging and to determine their interactions with environmental, health and physiological factors that can precipitate memory loss and increase susceptibility to related neurological disorders, such as Alzheimer’s disease (AD).

How does chronic stress influence risk for memory loss and disease in aging? 

Stress is an ever-present, unpredictable and, often, unavoidable feature of daily life. The hypothalamic-pituitary-adrenal (HPA) axis coordinates behavioral and cellular responses to stressful experiences via secretion of glucocorticoids. The prefrontal cortex and hippocampus collectively express high levels of glucocorticoid receptors that impart regulatory influences upon HPA axis activity, but also render these structures susceptible to dysregulated glucocorticoid secretion that accompanies normal aging or following chronic stress. We are investigating whether stress increases susceptibility to memory loss in aging through glucocorticoid-mediated epigenetic modifications and examining the protective effects of attenuating glucocorticoid signaling during stressful experiences across the lifespan.

Can diet build neural resilience and cognitive reserve against aging and stress? 

While age-associated insulin resistance induces an overabundance of circulating glucose, the chief energy source fueling cellular respiration, glucose utilization is depressed in the aging and AD brain. However, the capacity of the brain to metabolize fat-derived ketones does not decline with age or in AD and consumption of a high fat/low carbohydrate “ketogenic” diet normalizes expression of synaptic proteins and improves cognition in aging. We are now testing the hypothesis that diet-based strategies to induce ketosis improve cognition in aging by rejuvenating synaptic mitochondria and increasing the efficiency of oxidative phosphorylation. Additionally, we are exploring whether such dietary interventions are effective in regulating glucose signaling stimulated by glucocorticoid secretion and protect against the effects of stress on brain aging and metabolic health.

Can we optimize existing pharmacotherapies for treatment of age- and stress-related impairments? 

NMDA receptor (NMDAR) antagonists such as NAMENDA and esketamine are prescribed for treatment of AD and stress-related mental health disorders. However, their therapeutic mechanisms are unclear, their benefits are often temporary, and their side effects can be considerable. NMDARs are tetrameric ion channels comprised of variable subunits that determine channel properties, subcellular localization and coupling with other signaling proteins. Our lab is developing new approaches to investigate the interactions among NMDAR subunits with the goal of defining the spectrum of normal functions accomplished by various receptor configurations and to develop precision ligands that will correct NMDAR dysfunction that emerges in aging, AD, and neuropsychiatric disorders.

Recent Publications:

Braunstein PW, Horovitz DJ, Hampton AM, Hollis F, Newman LA, Enos RT, McQuail JA. Daily fluctuations in blood glucose with normal aging are inversely related to hippocampal synaptic mitochondrial proteins. Aging Brain. 2024 Apr 5;5:100116. doi: 10.1016/j.nbas.2024.100116. PMID: 38596458; PMCID: PMC11002859.

Gandy HM, Hollis F, Hernandez CM, McQuail JA. Aging or chronic stress impairs working memory and modulates GABA and glutamate gene expression in prelimbic cortex. Front Aging Neurosci. 2024 Jan 8;15:1306496. doi: 10.3389/fnagi.2023.1306496. PMID: 38259638; PMCID: PMC10800675.

Burzynski HE, Ayala KE, Frick MA, Dufala HA, Woodruff JL, Macht VA, Eberl BR, Hollis F, McQuail JA, Grillo CA, Fadel JR, Reagan LP. Delayed cognitive impairments in a rat model of Gulf War Illness are stimulus-dependent. Brain Behav Immun. 2023 Oct;113:248-258. doi: 10.1016/j.bbi.2023.07.003. Epub 2023 Jul 10. PMID: 37437820; PMCID: PMC10530066.

Hernandez CM, McQuail JA, Ten Eyck TW, Wheeler AR, Labiste CC, Setlow B, Bizon JL. GABAB receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age. Neuropharmacology. 2022 May 15;209:109001. doi: 10.1016/j.neuropharm.2022.109001. Epub 2022 Feb 19. PMID: 35189132; PMCID: PMC9297337.

McQuail JA, Beas BS, Kelly KB, Hernandez CM 3rd, Bizon JL, Frazier CJ. Attenuated NMDAR signaling on fast-spiking interneurons in prefrontal cortex contributes to age-related decline of cognitive flexibility. Neuropharmacology. 2021 Oct 1;197:108720. doi: 10.1016/j.neuropharm.2021.108720. Epub 2021 Jul 15. PMID: 34273386; PMCID: PMC8478839.

McQuail JA, Dunn AR, Stern Y, Barnes CA, Kempermann G, Rapp PR, Kaczorowski CC, Foster TC. Cognitive Reserve in Model Systems for Mechanistic Discovery: The Importance of Longitudinal Studies. Front Aging Neurosci. 2021 Jan 21;12:607685. doi: 10.3389/fnagi.2020.607685. PMID: 33551788; PMCID: PMC7859530.

Hernandez AR, Hernandez CM, Truckenbrod LM, Campos KT, McQuail JA, Bizon JL, Burke SN. Age and Ketogenic Diet Have Dissociable Effects on Synapse-Related Gene Expression Between Hippocampal Subregions. Front Aging Neurosci. 2019 Sep 13;11:239. doi: 10.3389/fnagi.2019.00239. PMID: 31607897; PMCID: PMC6755342.

Hernandez AR, Hernandez CM, Campos K, Truckenbrod L, Federico Q, Moon B, McQuail JA, Maurer AP, Bizon JL, Burke SN. A Ketogenic Diet Improves Cognition and Has Biochemical Effects in Prefrontal Cortex That Are Dissociable From Hippocampus. Front Aging Neurosci. 2018 Dec 3;10:391. doi: 10.3389/fnagi.2018.00391. PMID: 30559660; PMCID: PMC6286979.

McQuail JA, Krause EG, Setlow B, Scheuer DA, Bizon JL. Stress-induced corticosterone secretion covaries with working memory in aging. Neurobiol Aging. 2018 Nov;71:156-160. doi: 10.1016/j.neurobiolaging.2018.07.015. Epub 2018 Jul 30. PMID: 30144648; PMCID: PMC6162104.

Hernandez CM, McQuail JA, Schwabe MR, Burke SN, Setlow B, Bizon JL. Age-Related Declines in Prefrontal Cortical Expression of Metabotropic Glutamate Receptors that Support Working Memory. eNeuro. 2018 Jun 28;5(3):ENEURO.0164-18.2018. doi: 10.1523/ENEURO.0164-18.2018. PMID: 29971246; PMCID: PMC6026020.

Hernandez AR, Hernandez CM, Campos KT, Truckenbrod LM, Sakarya Y, McQuail JA, Carter CS, Bizon JL, Maurer AP, Burke SN. The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats. J Gerontol A Biol Sci Med Sci. 2018 Mar 14;73(4):450-458. doi: 10.1093/gerona/glx193. PMID: 29040389; PMCID: PMC5861916.

Hernandez CM, Vetere LM, Orsini CA, McQuail JA, Maurer AP, Burke SN, Setlow B, Bizon JL. Decline of prefrontal cortical-mediated executive functions but attenuated delay discounting in aged Fischer 344 × Brown Norway hybrid rats. Neurobiol Aging. 2017 Dec;60:141-152. doi: 10.1016/j.neurobiolaging.2017.08.025. Epub 2017 Sep 5. PMID: 28946018; PMCID: PMC5669385.

McQuail JA, Beas BS, Kelly KB, Simpson KL, Frazier CJ, Setlow B, Bizon JL. NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline. J Neurosci. 2016 Dec 14;36(50):12537-12548. doi: 10.1523/JNEUROSCI.2332-16.2016. Epub 2016 Nov 2. PMID: 27807032; PMCID: PMC5157101.

Beas BS, McQuail JA, Banuelos C, Setlow B, Bizon JL. Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats. Neuroscience. 2017 Mar 14;345:274-286. doi: 10.1016/j.neuroscience.2016.02.014. Epub 2016 Feb 9. PMID: 26873002; PMCID: PMC5333995.

McQuail JA, Frazier CJ, Bizon JL. Molecular aspects of age-related cognitive decline: the role of GABA signaling. Trends Mol Med. 2015 Jul;21(7):450-60. doi: 10.1016/j.molmed.2015.05.002. Epub 2015 Jun 9. PMID: 26070271; PMCID: PMC4500156.

McQuail JA, Nicolle MM. Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats. Neurobiol Aging. 2015 Jan;36(1):323-33. doi: 10.1016/j.neurobiolaging.2014.06.030. Epub 2014 Jul 3. PMID: 25086838; PMCID: PMC4268167.

Complete list of Dr. McQuail's Published Work can be found on PubMed

Join the Lab

USC Undergraduates

Our lab is an ideal site to launch your career in neuroscience! Students in our lab receive hands-on training, participate in regular scientific discussions, and hone professional skills. Students can fulfill independent research requirements (i.e., 399) in the lab, apply for and win undergraduate and national research fellowships, write an honors thesis (i.e., 499), and make scientific presentations at local and international meetings. Alumni from our lab advance to training in graduate or medical school or find employment in academia or industry. Interested USC undergraduates can use this link to contact Dr. McQuail.

Current or Prospective Graduate Students

• Motivated and qualified M.S. or Ph.D. candidates should apply to the School of Medicine’s Biomedical Sciences Program. In your personal statement, please expand on your specific interests in connection with our research program and how training within our lab/department/program will help you to achieve your professional goals. Candidates may contact Dr. McQuail directly by email during the preparation of their application or at any point throughout the application process to improve your knowledge of the lab and its role in the training program.
• Interested post-baccalaureate students should apply via USC PREP. Again, please clearly indicate your interest in our lab in your personal statement to facilitate the review process.
• First-year medical students interested in our research may apply to the SOAR Program. Please contact Dr. McQuail prior to submitting any application so we can collaborate to identify a suitable research project. We also train students in the combined M.D./Ph.D. program; applications are considered from current second-year medical students after acquiring research experience in the lab via SOAR.

Postdoctoral Candidates

Highly qualified Ph.D. recipients or advanced Ph.D. students with demonstrated scientific contributions in the areas of behavioral neuroscience, cognitive aging, stress neurobiology, and/or AD pathogenesis are welcome to send their CV by email to Dr. McQuail for consideration. Any consideration is contingent upon initial availability of grant funds and a clear and credible plan to acquire individual funding that supports continued training at the post-doctoral or mentored faculty levels (i.e., NIH F32, K99, or K01).