Areas of Interest
- Synaptic structure and function
- Astrocyte control of synaptic transmission
- Synaptic basis of neuropsychiatric disorders
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 in the lab is 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?
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
Regulation of glutamate, GABA and dopamine transporters’ uptake, surface mobility and expression. Ryan RM, Ingram SL, Scimemi A. Front Cell Neurosci. 2021 Apr 13. PMID: 33927596
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 Sep 18. PMID: 33053337. In the news (1): Times Union (July 14, 2020), (2): Congressman Paul Tonko press release (July 13, 2020), On the radio: WAMC-NPR
Current knowledge of Slc6a1-related disorders: GABA transporter (GAT1) mediated disorders. Goodspeed K, Pérez-Palma E, Iqbal S, Cooper D, Scimemi A, Johannesen KM, Stefanski A, Demarest S, Helbig K, Kang J, Prentice B, Brownsteint C, Byung CL, Helbig I, De Los Reyes E, McKnight D, Crunelli V, Campbell AJ, Møller RS, Freed A, Lal D. Brain Comm. 2020 Sep 15. PMID: 33241211
- 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 Free PMC Article
- 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. PMID: 29229708
- Rădulescu A, Heron J, Kennedy C, Scimemi A (2017) Global and local excitation and inhibition shape the dynamics of the cortico-striatal-thalamo-cortical pathway, Sci Rep. 2017 Aug 8;7(1):7608. doi: 10.1038/s41598-017-07527-8. PMID: 28790376.
- Sweeney AM, Fleming KE, McCauley JP, Rodriguez MF, Martin ET, Sousa AA, Leapman RD, Scimemi A (2017) PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology, Sci Rep. 2017 Mar 3;7:43606. doi: 10.1038/srep43606. PMID: 28256580.
- Reeves SL, Fleming KE, Zhang L, Scimemi A (2016) M-Track: A New Softwarefor Automated Detection of Grooming Trajectories in Mice, PLoS Comput Biol. Sep. 16; 12(9):e1005115. doi: 10:1371/journal.pcbi.1005115. PMID: 27636358.
- Scimemi A. (2014) Structure, function and plasticity of GABA transporters Front Cell Neurosci.8:161.
- Scimemi A. (2014) Plasticity of GABA transporters: an unconventional route to shape inhibitory synaptic transmission. . Front Cell Neurosci. 8:128.
- Scimemi A, Diamond JS (2013). Deriving the time course of glutamate clearance with a deconvolution analysis of astrocytic transporter currents. J Vis Exp. (78).
- Scimemi A, Meabon JS, Woltjer RL, Sullivan JM, Diamond JS, Cook DG (2013). Amyloid-β1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. J Neurosci33(12):5312-5318.
- Scimemi A (2013). A TRP among the astrocytes. J Physiol 591(Pt 1):9-15.
- Scimemi A, Diamond JS (2012).The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from Schaffer collateral synapses. J Neurosci 32(50):18157-76.
- Chaudhry C, Scimemi A, Kumar J (2011). Building and breaking interfaces: how a receptor takes shape. J Neurosci 31(30):10749-51.
- Pavlov I, Scimemi A, Savtchenko L, Kullmann DM, Walker MC (2011). I(h)-mediated depolarization enhances the temporal precision of neuronal integration. Nat Commun 2:199.
- Scimemi A, Tian H, Diamond JS (2009). Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus. J Neurosci 29(46):14581-95.
- Scimemi A, Beato M (2009). Determining the neurotransmitter concentration profile at active synapses. Mol Neurobiol 40(3):289-306.
- Scimemi A (2009). The interrelated lives of NMDA receptors and glycine transporters. J Physiol587(Pt 13):3061-2.
- Scimemi A (2008). Anchors aweigh: NMDA receptors set sail from their presynaptic port. J Physiol586(Pt 20):4787.
- Zheng K, Scimemi A, Rusakov DA (2008). Receptor actions of synaptically released glutamate: the role of transporters on the scale from nanometers to microns. Biophys J 95(10):4584-96.
- Plested AJ, Ashby MC, Scimemi A (2007). Getting hot under the calyx. J Physiol 580(Pt 1):13-4.
- Scimemi A, Andersson A, Heeroma JH, Strandberg J, Rydenhag B, McEvoy AW, Thom M, Asztely F, Walker MC (2006). Tonic GABA(A) receptor-mediated currents in human brain. Eur J Neurosci24(4):1157-60.
- Scimemi A, Schorge S, Kullmann DM, Walker MC (2006). Epileptogenesis is associated with enhanced glutamatergic transmission in the perforant path. J Neurophysiol 95(2):1213-20.
- Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC (2005). Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 25(43):10016-24.
- Rusakov DA, Scimemi A, Walker MC, Kullmann DM (2004). Comment on "Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity". Science 305(5692):1912
- Scimemi A, Fine A, Kullmann DM, Rusakov DA (2004). NR2B-containing receptors mediate cross talk among hippocampal synapses. J Neurosci 24(20):4767-77.
- Pellegrino M, Pellegrini M, Bigini P, Scimemi A (1998). Properties of Ca2+-activated K+ channels in erythrocytes from patients with myotonic muscular dystrophy. Muscle & Nerve 21(11):1465-72.