The brain transduces sensory stimuli, processes information and stores memory within large networks of neurons linked together by synaptic connections. Our laboratory is working to understand what particular features of synapses affect their strength, reliability and independence, and how these attributes contribute to their role in the function of the network. Specifically, we study how the relative location and number of calcium channels and vesicle release sites in the presynaptic terminals of CA1 synapses may influence short-term plasticity of synaptic transmission. We find that depletion shapes the relative size of response pairs even at low-probability synapses, due to uneven recruitment of release sites within single active zones. This work has been published in the Journal of Neuroscience. We also have forged a collaboration with David Cook at the University of Washington to measure quantitatively the time course of glutamate uptake in a mouse model of Alzheimer's Disease. We find that A beta peptide, a critical molecular component of the disease, reduces glutamate transport by inducing internalization, ubiquitination and aggregation of the glutamate transporter GLT-1. Furthermore, this effect is inhibited by antioxidants, including Vitamin E analogs. A manuscript has been published in the Journal of Neuroscience. Finally, we have begin to collaborate with Stephen Traynelis at Emory University to examine the role of protease-activated receptor 1 (PAR-1) on synaptic transmission, particularly on synaptic ultrastructure and glutamate uptake. We find that PAR-1 speeds the clearance of synaptically released glutamate. Interestingly, this does not appear to reflect an increase in uptake capacity, suggesting that PAR-1 may have effects on synaptic ultrastructure. A manuscript is in preparation.
|Scimemi, Annalisa; Meabon, James S; Woltjer, Randall L et al. (2013) Amyloid-Î²1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. J Neurosci 33:5312-8|
|Scimemi, Annalisa; Diamond, Jeffrey S (2013) Deriving the time course of glutamate clearance with a deconvolution analysis of astrocytic transporter currents. J Vis Exp :|
|Scimemi, Annalisa; Diamond, Jeffrey S (2012) The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from Schaffer collateral synapses. J Neurosci 32:18157-76|