A. Kimberley McAllister, Ph.D.

Cellular and molecular mechanisms of synapse formation and plasticity in cortical development and disease

Research in my laboratory focuses on understanding the cellular and molecular mechanisms of synapse formation and refinement during development and in disease. We use an arsenal of approaches, including development of new techniques, to address these questions both in vivo and in vitro. We have pioneered time-lapse imaging approaches to study protein transport before and during synapse formation and, most recently, synapse dynamics using a novel long-term imaging assay.

My laboratory is also one of only a few labs that study how “immune” molecules, such as MHCI and cytokines, regulate the initial establishment of cortical connections. We have found that MHCI molecules and interleukin-1 receptors are present at developing synapses, where they negatively regulate synapses.  Ongoing efforts aim to identify the molecular mechanisms that underlie these effects and identify the signaling molecules that act upstream of these synaptic immune molecules to cause synapse loss in development and in disease models.  Finally, we recently launched a new research direction into Alzheimer’s disease research focusing on the role for MHCI molecules in neurodegeneration. We have found that MHCI mediates Ab-induced synapse loss and cognitive deficits both in vivo and in vitro.

Since these immune molecules are implicated in several neurodevelopmental disorders, including autism and schizophrenia, MHCI molecules could mediate the effects of the environment on cortical connectivity both during normal development and in disease. Indeed, we have found that MHCI and cytokines mediate the effects of maternal infection in causing behavioral alterations in offspring.  In parallel to our basic research in neuroimmunology, we also work in translational neuroscience through leading a multi-disciplinary collaboration between eight groups at UC Davis, funded initially by a UC Davis RISE Pilot Center grant and transformed into an NIMH Conte Center, which was recently renewed. Through this center, we have identified proteins in female mice before pregnancy and following maternal immune activation that predict susceptibility and resilience to schizophrenia- and autism-related behavioral and neurochemical alterations in offspring. We are currently using this information to test biomarkers and new treatments to identify susceptible pregnancies and prevent the effects of maternal infection on brain development and behavior in offspring.

Prendergast K, McAllister AK. Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring. J Vis Exp. 2022 Aug 17;(186). doi: 10.3791/64095. PMID: 36063000.

Page NF, Gandal MJ, Estes ML, Cameron S, Buth J, Parhami S, Ramaswami G, Murray K, Amaral DG, Van de Water JA, Schumann CM, Carter CS, Bauman MD, McAllister AK, Geschwind DH. Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates. Biol Psychiatry. 2021 May 1;89(9):896-910. doi: 10.1016/j.biopsych.2020.10.016. Epub 2020 Nov 2. PMID: 33386132; PMCID: PMC8052273.

Canales CP, Estes ML, Cichewicz K, Angara K, Aboubechara JP, Cameron S, Prendergast K, Su-Feher L, Zdilar I, Kreun EJ, Connolly EC, Seo JM, Goon JB, Farrelly K, Stradleigh TW, van der List D, Haapanen L, Van de Water J, Vogt D, McAllister AK, Nord AS. Sequential perturbations to mouse corticogenesis following in utero maternal immune activation. Elife. 2021 Mar 5;10:e60100. doi: 10.7554/eLife.60100. PMID: 33666173; PMCID: PMC7979158.

Vlasova RM, Iosif AM, Ryan AM, Funk LH, Murai T, Chen S, Lesh TA, Rowland DJ, Bennett J, Hogrefe CE, Maddock RJ, Gandal MJ, Geschwind DH, Schumann CM, Van de Water J, McAllister AK, Carter CS, Styner MA, Amaral DG, Bauman MD. Maternal Immune Activation during Pregnancy Alters Postnatal Brain Growth and Cognitive Development in Nonhuman Primate Offspring. J Neurosci. 2021 Dec 1;41(48):9971-9987. doi: 10.1523/JNEUROSCI.0378-21.2021. Epub 2021 Oct 4. PMID: 34607967; PMCID: PMC8638691.

Estes ML, Prendergast K, MacMahon JA, Cameron S, Aboubechara JP, Farrelly K, Sell GL, Haapanen L, Schauer JD, Horta A, Shaffer IC, Le CT, Kincheloe GN, Tan DJ, van der List D, Bauman MD, Carter CS, Van de Water J, McAllister AK. Baseline immunoreactivity before pregnancy and poly(I:C) dose combine to dictate susceptibility and resilience of offspring to maternal immune activation. Brain Behav Immun. 2020 Aug;88:619-630. doi: 10.1016/j.bbi.2020.04.061. Epub 2020 Apr 23. PMID: 32335198; PMCID: PMC7415552.

Bauman MD, Lesh TA, Rowland DJ, Schumann CM, Smucny J, Kukis DL, Cherry SR, McAllister AK, Carter CS. Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation. Transl Psychiatry. 2019 Apr 12;9(1):135. doi: 10.1038/s41398-019-0449-y. PMID: 30979867; PMCID: PMC6461624.

Kentner AC, Bilbo SD, Brown AS, Hsiao EY, McAllister AK, Meyer U, Pearce BD, Pletnikov MV, Yolken RH, Bauman MD. Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model. Neuropsychopharmacology. 2019 Jan;44(2):245-258. doi: 10.1038/s41386-018-0185-7. Epub 2018 Aug 21. PMID: 30188509; PMCID: PMC6300528.

Estes ML, McAllister AK. Maternal immune activation: Implications for neuropsychiatric disorders. Science. 2016 Aug 19;353(6301):772-7. doi: 10.1126/science.aag3194. PMID: 27540164; PMCID: PMC5650490.

Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci. 2015 Aug;16(8):469-86. doi: 10.1038/nrn3978. PMID: 26189694; PMCID: PMC5650494.

Estes ML, McAllister AK. Alterations in immune cells and mediators in the brain: it's not always neuroinflammation! Brain Pathol. 2014 Nov;24(6):623-30. doi: 10.1111/bpa.12198. PMID: 25345893; PMCID: PMC4365495.

Elmer BM, Estes ML, Barrow SL, McAllister AK. MHCI requires MEF2 transcription factors to negatively regulate synapse density during development and in disease. J Neurosci. 2013 Aug 21;33(34):13791-804. doi: 10.1523/JNEUROSCI.2366-13.2013. PMID: 23966700; PMCID: PMC3755720.

Elmer BM, McAllister AK. Major histocompatibility complex class I proteins in brain development and plasticity. Trends Neurosci. 2012 Nov;35(11):660-70. doi: 10.1016/j.tins.2012.08.001. Epub 2012 Aug 30. PMID: 22939644; PMCID: PMC3493469.

Garay PA, Hsiao EY, Patterson PH, McAllister AK. Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain Behav Immun. 2013 Jul;31:54-68. doi: 10.1016/j.bbi.2012.07.008. Epub 2012 Jul 25. PMID: 22841693; PMCID: PMC3529133.

Glynn MW, Elmer BM, Garay PA, Liu XB, Needleman LA, El-Sabeawy F, McAllister AK. MHCI negatively regulates synapse density during the establishment of cortical connections. Nat Neurosci. 2011 Apr;14(4):442-51. doi: 10.1038/nn.2764. Epub 2011 Feb 27. PMID: 21358642; PMCID: PMC3251641.

Needleman LA, Liu XB, El-Sabeawy F, Jones EG, McAllister AK. MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16999-7004. doi: 10.1073/pnas.1006087107. Epub 2010 Sep 13. PMID: 20837535; PMCID: PMC2947898

Barrow SL, Constable JR, Clark E, El-Sabeawy F, McAllister AK*, and Washbourne PW* (2009) Neuroligin 1: a cell adhesion molecule that recruits PSD-95 and NMDA receptors by distinct mechanisms during synaptogenesis. Neural Development May 18; 4:17.

McAllister AK (2007) Molecular mechanisms of CNS synapse formation. Annual Reviews of Neuroscience 30:425-450.

Gomes R, Hampton C, and McAllister AK. (2006) TrkB and synaptic proteins are colocalized and transported together during development of cortical neurons. Journal of Neuroscience 26: 11487-500.

Sabo SL, Gomes RG, and McAllister AK. (2006) Selective formation of synapses at defined sites along the axon shaft. Journal of Neuroscience 26: 10813- 10825.

Washbourne PW, Liu X-B, Jones EG, and McAllister AK (2004) Exo/endocytic cycling of NMDA receptors during trafficking in neurons before synapse formation. Journal of Neuroscience, 24:8253-8264.

Sabo SL and McAllister AK (2003) Mobility and cycling of synaptic protein-containing vesicles in axonal growth cone filopodia, Nature Neuroscience 6: 1264-1269.

Washbourne P, Bennett JE, and McAllister AK (2002) Rapid recruitment of NMDA receptor transport packets to nascent synapses. Nature Neuroscience 5: 751-759.

• Department of Neurology
• Neurobiology, Physiology and Behavior
• Center for Neuroengineering and Medicine
• MIND Institute
• Institute for Psychedelics and Neurotherapeutics
• Neuroscience Graduate Group