Activity-dependent modulations of synaptic transmission are important mechanisms of information processing and storage in neuronal circuits. A variety of related but mechanistically distinct forms of synaptic plasticity have been described in in vitro preparations of brain slices.

A major goal of my laboratory is to elucidate the underlying molecular events, leading to and regulating changes in synaptic efficacy. Newly developed techniques of molecular replacement, using mouse genetics and/or viral-mediated gene transfer allow us to manipulate the molecular composition of single neurons in a spatial and temporal controlled manner.

In particular, we are able to investigate the effects of heterologously expressed proteins on the background of wild-type neurons, or neurons, in which the endogenous protein expression is diminished. We combine this technique with simultaneous dual whole cell patch clamp recordings from rodent brain slices to monitor changes in synaptic efficacy in the manipulated cell in comparison to the neighboring control cell.

Knowledge gained from the understanding of molecular mechanisms of synaptic transmission and plasticity will ultimately provide important clues for the function of neuronal ircuits and potentially the functioning of the brain.

1.    Brown TE, Lee BR, Mu P, Ferguson D, Dietz D, Ohnishi YN, Lin Y, Suska A, Ishikawa M, Huang YH, Shen H, Kalivas PW, Sorg BA, Zukin RS, Nestler EJ, Dong Y, Schlüter OM (2011) A silent synapse-based mechanism for cocaine-induced locomotor sensitization. J Neurosci. 31(22):8163-74.

2.    Mu P, Neumann PA, Panksepp J, Schlüter OM, Dong Y (2011) Exposure to Cocaine Alters Dynorphin-Mediated Regulation of Excitatory Synaptic Transmission in Nucleus Accumbens Neurons. Biol Psychiatry., 69(3):228-35.

3.    Huang YH, Schlüter OM, Dong Y (2011) Cocaine-induced homeostatic regulation and dysregulation of nucleus accumbens neurons. Behav Brain Res., 216(1):9-18.

4.    Fiala A, Suska A, Schlüter OM (2010) Optogenetic Approaches in Neuroscience. Cur Biol. 20(20):R897-903.

5.    Schonn JS, van Weering JR, Mohrmann R, Schlüter OM, Südhof TC, de Wit H, Verhage M, Sørensen JB (2010) Rab3 Proteins Involved in Vesicle Biogenesis and Priming in Embryonic Mouse Chromaffin Cells. Traffic, 11(11):1415-28.

6.    Siebert H, Kahle PJ, Kramer ML, Isik T, Schlüter OM, Schulz-Schaeffer WJ, Brück W (2010) Over-expression of alpha-synuclein in the nervous system enhances axonal degeneration after peripheral nerve lesion in a transgenic mouse strain. J Neurochem. 114(4):1007-18.

7.    Mu P, Moyer JT, Ishikawa M., Zhang Y., Panksepp J., Sorg BA, Schlüter OM, Dong Y (2010) Exposure to Cocaine Dynamically Regulates the Intrinsic Membrane Excitability of Nucleus Accumbens Neurons. J Neurosci. 30(10):3689-99.

8.    Huang YH, Lin Y, Mu P, Lee BR, Brown TE, Wayman G, Marie H, Liu W, Yan Z, Sorg BA, Schlüter OM, Zukin RS, Dong Y (2009) In vivo cocaine experience generates silent synapses. Neuron 63(1):40-7.

9.    Ishikawa M, Moyer J, Wolf J, Mu P, Quock R, Davies N, Hu X-T, Schlüter OM, Dong Y (2009) Homeostatic Synapse-driven Membrane Plasticity in Nucleus Accumbens Neurons. J Neurosci, 29(18):5820-31.

10.  Bhattacharyya S, Biou V, Xu W, Schlüter O, Malenka RC (2009) A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nat Neurosci; 12(2):172-81.

11.  Gallardo G., Schlüter OM, Südhof TC (2008) A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides. Nat Neurosci; 11(3):301-8.

12.  Xu* W, Schlüter* OM, Steiner P, Czervionke BL, Sabatini B, Malenka RC (2008) Molecular Dissociation of the Role of PSD-95 in Regulating Synaptic Strength and LTD. Neuron; 57(2):248-62.

13.  Schlüter* OM, Xu* W, Malenka RC (2006) Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent regulation of synaptic AMPA receptor function. Neuron; 51(1):99-111.

14.  Schlüter OM, Basu J, Südhof TC, Rosenmund C (2006) Rab3 superprimes synaptic vesicles for release: implications for short-term synaptic plasticity. J Neurosci; 26(4):1239-46.

15.  Chandra S, Gallardo G, Fernandez-Chacon R, Schlüter OM, Südhof TC (2005) Alpha-synuclein cooperates with CSPa in preventing neurodegeneration. Cell; 123(3):383-96.

16.  Fornai, F, Schlüter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G, Pellegrini A, Nicoletti F, Ruggieri S, Paparelli A, Südhof TC (2005) Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and a-synuclein. PNAS; 102(9):3413-18.

17.  Schlüter OM, Schmitz F, Jahn R, Rosenmund C, Südhof TC. A complete genetic analysis of neuronal Rab3 function. (2004) J Neurosci. 24(29):6629-37.

18.  Schlüter OM, Fornai F, Alessandrí MG, Takamori S, Geppert M, Jahn R, Südhof TC. (2003) Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience. 118(4):985-1002.

19.  Schlüter OM, Khvotchev M, Jahn R, Südhof TC. (2002) Localization versus function of Rab3 proteins. Evidence for a common regulatory role in controlling fusion. J Biol Chem. 277(43):40919-29.

20.  Schlüter OM, Schnell E, Verhage M, Tzonopoulos T, Nicoll RA, Janz R, Malenka RC, Geppert M, Südhof TC. (1999) Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release. J Neurosci. 19(14)5834-46