Annalisa Scimemi

Associate Professor
Department of Biological Sciences
Department of Nanoscale Science & Engineering
Annalisa Scimemi
Education

PhD, International School for Advanced Studies (SISSA/ISAS), Trieste

About

Research

The brain regulates every aspect of our daily life, yet many of the fundamental mechanisms underlying its function remain unclear. How do neurons in the brain exchange information among each other? How is their activity conveyed across neurons in different brain regions and how is it shaped by astrocytes?

In our lab, we are interested in understanding the functional properties of central synapses, the specialized structures that convert the electrical activity of a neuron into a chemical signal for its target cells. We want to understand how individual molecules are distributed within the synapse and how their spatial arrangement influences the properties of neurotransmitter release. We want to know how neurotransmitters diffuse outside of the synapse and generate long-distance signals to different cells. Our ultimate goal is to gain insights into the functional consequences of changes in synaptic function associated with the onset of different neuropsychiatric and neurodenegerative disorders.

To perform our studies, we use a combination of experimental and theoretical approaches, including electrophysiology, optogenetics, two-photon imaging and reaction-diffusion computer simulations. We are also eager to learn and develop novel experimental approaches and research tools.

 

Research Interests

Research currently designed to address the following questions:

  • How are individual molecules are distributed within presynaptic terminals and how does their distribution influences the properties of neurotransmitter release from small central synapses?
  • How do astrocytes regulate the spread of synaptic signals in the brain?
  • How do changes in the activity of cortical synaptic circuits lead to the onset of neuropsychiatric and neurodegenerative diseases?
Publications
  • Dopamine-Glutamate and Dopamine-GABA Co-release, Scimemi A. Adv Neurobiol. 2025;46:197-214. doi: 10.1007/978-3-031-96364-3_8. PMID: 41051711
  • An increased excitation and inhibition onto CA1 pyramidal cells sets the path to Alzheimer's disease, Wehrle PH, Rathwell TJ, Petroccione MA, Caiazza ED, Manning AK, Frasson Dos Reis L, Todd GC, Affinnih N, Ahmad S, Mehdi H, Tschang IL, Hassan U, Tsakh BR, Lauffer MC, Rosenberg PA, Darvas M, Cook DG, Scimemi A. bioRxiv [Preprint]. 2025 Jun 27:2025.05.27.656417. doi: 10.1101/2025.05.27.656417. PMID: 40501909
  • An unsuspected physiological role for mGluRIII glutamate receptors in hippocampal area CA1, Petroccione MA, Melone M, Rathwell TJ, Dwivedi N, Grienberger C, Conti F, Scimemi A. bioRxiv [Preprint]. 2025 Mar 31:2025.03.31.646479. doi: 10.1101/2025.03.31.646479. PMID: 40236245
  • Neuronal glutamate transporters control reciprocal inhibition and gain modulation in D1 medium spiny neurons, Petroccione MA, D'Brant LY, Affinnih N, Wehrle PH, Todd GC, Zahid S, Chesbro HE, Tschang IL, Scimemi A. Elife. 2023 Jul 12;12:e81830. doi: 10.7554/eLife.81830. PMID: 37435808
  • NRN-EZ: an application to streamline biophysical modeling of synaptic integration using NEURON, Cobb EAW, Petroccione MA, Scimemi A. Sci Rep. 2023 Jan 10;13(1):464. doi: 10.1038/s41598-022-27302-8. PMID: 36627356
  • Editorial: Biology of brain disorders-Cellular substrates for disrupted synaptic function and experience-dependent plasticity, Tropea D, Scimemi A, Banerjee A. Front Cell Neurosci. 2022 Aug 10;16:947926. doi: 10.3389/fncel.2022.947926. eCollection 2022. PMID: 36035263
  • Control of complex behavior by astrocytes and microglia, Ortinski PI, Reissner KJ, Turner J, Anderson TA, Scimemi A. Neurosci Biobehav Rev. 2022 Jun;137:104651. doi: 10.1016/j.neubiorev.2022.104651. Epub 2022 Apr 1. PMID: 35367512
  • Estimating the glutamate transporter surface density in distinct sub-cellular compartments of mouse hippocampal astrocytes, Rǎdulescu AR, Todd GC, Williams CL, Bennink BA, Lemus AA, Chesbro HE, Bourgeois JR, Kopec AM, Zuloaga DG, Scimemi A. PLoS Comput Biol. 2022 Feb 4;18(2):e1009845. doi: 10.1371/journal.pcbi.1009845. eCollection 2022 Feb. PMID: 35120128
  • Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A, Wilson CS, Dohare P, Orbeta S, Nalwalk JW, Huang Y, Ferland RJ, Sah R, Scimemi A, Mongin AA. FASEB J. 2021 Oct;35(10):e21869. doi: 10.1096/fj.202002745R. PMID: 34469026
  • Transplantable human motor networks as a neuron-directed strategy for spinal cord injury, Olmsted ZT, Stigliano C, Scimemi A, Wolfe T, Cibelli J, Horner PJ, Paluh JL. iScience. 2021 Jul 10;24(8):102827. doi: 10.1016/j.isci.2021.102827. eCollection 2021 Aug 20. PMID: 34381965
  • Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression, Ryan RM, Ingram SL, Scimemi A. Front Cell Neurosci. 2021 Apr 13;15:670346. doi: 10.3389/fncel.2021.670346. eCollection 2021. PMID: 33927596
  • Current knowledge of SLC6A1-related neurodevelopmental disorders, Goodspeed K, Pérez-Palma E, Iqbal S, Cooper D, Scimemi A, Johannesen KM, Stefanski A, Demarest S, Helbig KL, Kang J, Shaffo FC, Prentice B, Brownstein CA, Lim B, Helbig I, De Los Reyes E, McKnight D, Crunelli V, Campbell AJ, Møller RS, Freed A, Lal D. Brain Commun. 2020 Oct 13;2(2):fcaa170. doi: 10.1093/braincomms/fcaa170. eCollection 2020. PMID: 33241211
  • Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1, McCauley JP, Petroccione MA, D'Brant LY, Todd GC, Affinnih N, Wisnoski JJ, Zahid S, Shree S, Sousa AA, De Guzman RM, Migliore R, Brazhe A, Leapman RD, Khmaladze A, Semyanov A, Zuloaga DG, Migliore M, Scimemi A. Cell Rep. 2020 Oct 13;33(2):108255. doi: 10.1016/j.celrep.2020.108255. PMID: 33053337
  • Astrocytic Coverage of Dendritic Spines, Dendritic Shafts, and Axonal Boutons in Hippocampal Neuropil, Gavrilov N, Golyagina I, Brazhe A, Scimemi A, Turlapov V, Semyanov A. Front Cell Neurosci. 2018 Aug 17;12:248. doi: 10.3389/fncel.2018.00248. eCollection 2018. PMID: 30174590
  • NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate, Bhattacharya S, Ma Y, Dunn AR, Bradner JM, Scimemi A, Miller GW, Traynelis SF, Wichmann T. J Neurosci Res. 2018 Jul;96(7):1324-1335. doi: 10.1002/jnr.24230. Epub 2018 Mar 25. PMID: 29577359
  • Astrocytes and the Warning Signs of Intracerebral Hemorrhagic Stroke, Scimemi A. Neural Plast. 2018 Feb 4;2018:7301623. doi: 10.1155/2018/7301623. eCollection 2018. PMID: 29531526
  • Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates, Singh A, Jenkins MA, Burke KJ Jr, Beck G, Jenkins A, Scimemi A, Traynelis SF, Papa SM. Cell Rep. 2018 Jan 23;22(4):941-952. doi: 10.1016/j.celrep.2017.12.095. Epub 2018 Jan 28. PMID: 29386136
  • Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors, Bellini S, Fleming KE, De M, McCauley JP, Petroccione MA, D'Brant LY, Tkachenko A, Kwon S, Jones LA, Scimemi A. J Neurosci. 2018 Jan 24;38(4):937-961. doi: 10.1523/JNEUROSCI.1906-17.2017. Epub 2017 Dec 11. PMID: 29229708
  • Global and local excitation and inhibition shape the dynamics of the cortico-striatal-thalamo-cortical pathway, Rădulescu A, Herron J, Kennedy C, Scimemi A. Sci Rep. 2017 Aug 8;7(1):7608. doi: 10.1038/s41598-017-07527-8. PMID: 28790376 
    PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology, Sweeney AM, Fleming KE, McCauley JP, Rodriguez MF, Martin ET, Sousa AA, Leapman RD, Scimemi A. Sci Rep. 2017 Mar 3;7:43606. doi: 10.1038/srep43606. PMID: 28256580
  • M-Track: A New Software for Automated Detection of Grooming Trajectories in Mice, Reeves SL, Fleming KE, Zhang L, Scimemi A. PLoS Comput Biol. 2016 Sep 16;12(9):e1005115. doi: 10.1371/journal.pcbi.1005115. eCollection 2016 Sep. PMID: 27636358
  • Structure, function, and plasticity of GABA transporters, Scimemi A. Front Cell Neurosci. 2014 Jun 17;8:161. doi: 10.3389/fncel.2014.00161. eCollection 2014. PMID: 24987330
  • Plasticity of GABA transporters: an unconventional route to shape inhibitory synaptic transmission, Scimemi A. Front Cell Neurosci. 2014 May 13;8:128. doi: 10.3389/fncel.2014.00128. eCollection 2014. PMID: 24860430
  • Deriving the time course of glutamate clearance with a deconvolution analysis of astrocytic transporter currents, Scimemi A, Diamond JS. J Vis Exp. 2013 Aug 7;(78):50708. doi: 10.3791/50708. PMID: 23963023
  • Amyloid-β1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1, Scimemi A, Meabon JS, Woltjer RL, Sullivan JM, Diamond JS, Cook DG. J Neurosci. 2013 Mar 20;33(12):5312-8. doi: 10.1523/JNEUROSCI.5274-12.2013. PMID: 23516295
  • The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from Schaffer collateral synapses, Scimemi A, Diamond JS. J Neurosci. 2012 Dec 12;32(50):18157-76. doi: 10.1523/JNEUROSCI.3827-12.2012. PMID: 23238730
  • A TRP among the astrocytes, Scimemi A. J Physiol. 2013 Jan 1;591(1):9-15. doi: 10.1113/jphysiol.2012.237883. Epub 2012 Oct 8. PMID: 23045334
  • Building and breaking interfaces: how a receptor takes shape, Chaudhry C, Scimemi A, Kumar J. J Neurosci. 2011 Jul 27;31(30):10749-51. doi: 10.1523/JNEUROSCI.2312-11.2011. PMID: 21795526
  • I(h)-mediated depolarization enhances the temporal precision of neuronal integration, Pavlov I, Scimemi A, Savtchenko L, Kullmann DM, Walker MC. Nat Commun. 2011 Feb 15;2:199. doi: 10.1038/ncomms1202. PMID: 21326231
  • Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus, Scimemi A, Tian H, Diamond JS. J Neurosci. 2009 Nov 18;29(46):14581-95. doi: 10.1523/JNEUROSCI.4845-09.2009. PMID: 19923291
  • Determining the neurotransmitter concentration profile at active synapses, Scimemi A, Beato M. Mol Neurobiol. 2009 Dec;40(3):289-306. doi: 10.1007/s12035-009-8087-7. Epub 2009 Oct 22. PMID: 19844813
  • The interrelated lives of NMDA receptors and glycine transporters, Scimemi A. J Physiol. 2009 Jul 1;587(Pt 13):3061-2. doi: 10.1113/jphysiol.2009.175976. PMID: 19567742 No abstract available.
  • Anchors aweigh: NMDA receptors set sail from their presynaptic port, Scimemi A. J Physiol. 2008 Oct 15;586(20):4787. doi: 10.1113/jphysiol.2008.162784. PMID: 18854432 No abstract available.
  • Receptor actions of synaptically released glutamate: the role of transporters on the scale from nanometers to microns, Zheng K, Scimemi A, Rusakov DA. Biophys J. 2008 Nov 15;95(10):4584-96. doi: 10.1529/biophysj.108.129874. Epub 2008 Aug 8. PMID: 18689452
  • Getting hot under the calyx, Plested AJ, Ashby MC, Scimemi A. J Physiol. 2007 Apr 1;580(Pt 1):13-4. doi: 10.1113/jphysiol.2007.129502. Epub 2007 Feb 15. PMID: 17303634 No abstract available.
  • Tonic GABA(A) receptor-mediated currents in human brain, Scimemi A, Andersson A, Heeroma JH, Strandberg J, Rydenhag B, McEvoy AW, Thom M, Asztely F, Walker MC. Eur J Neurosci. 2006 Aug;24(4):1157-60. doi: 10.1111/j.1460-9568.2006.04989.x. PMID: 16930441
  • Epileptogenesis is associated with enhanced glutamatergic transmission in the perforant path, Scimemi A, Schorge S, Kullmann DM, Walker MC. J Neurophysiol. 2006 Feb;95(2):1213-20. doi: 10.1152/jn.00680.2005. Epub 2005 Nov 9. PMID: 16282203.
  • Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus, Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC. J Neurosci. 2005 Oct 26;25(43):10016-24. doi: 10.1523/JNEUROSCI.2520-05.2005. PMID: 16251450
  • Comment on "Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity", Rusakov DA, Scimemi A, Walker MC, Kullmann DM. Science. 2004 Sep 24;305(5692):1912; author reply. doi: 10.1126/science.1102399. PMID: 15448254
  • NR2B-containing receptors mediate cross talk among hippocampal synapses, Scimemi A, Fine A, Kullmann DM, Rusakov DA. J Neurosci. 2004 May 19;24(20):4767-77. doi: 10.1523/JNEUROSCI.0364-04.2004. PMID: 15152037
  • Properties of Ca2+-activated K+ channels in erythrocytes from patients with myotonic muscular dystrophy, Pellegrino M, Pellegrini M, Bigini P, Scimemi A. Muscle Nerve. 1998 Nov;21(11):1465-72. doi: 10.1002/(sici)1097-4598(199811)21:11<1465::aid-mus15>3.0.co;2-#. PMID: 9771671