This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dendritic spines have traditionally been thought to serve primarily for biochemical compartmentalization but recent findings also attribute electrical compartmentalization to their morphology and possibly active ionic conductances (1 &2). The spine neck filters membrane potentials and such electrical isolation of dendritic spines from one another has been suggested to be the basis for linear integration of excitatory inputs (3). Using NEURON we investigate the effect of different morphological features of spines in an unbranched, cylindrical cable model as well as a morphologically realistic multi-compartmental model based on the reconstruction of an L5 pyramidal cell. We use morphological features described in recent electron microscopy (4) studies to constrain the parameters of synaptic spines and systematically test the impact of different spine features on dendritic and somatic excitatory postsynaptic potentials. Voltage filtering across the spine neck depends largely on the diameter and length of the spine neck as well as on the amplitude and duration of the synaptic event, but the experimentally observed effects cannot be explained easily from passive properties of the spine. In our model we explore the effect of different active conductances placed in the spine head and neck. With the help of high-dimensional data visualization techniques such as clutter based dimension re-ordering (5), we conduct exhaustive, multi-dimensional parameter searches (hopefully on teragrid) to predict the range of physiological parameters that can allow for the electrical properties as observed in experiments. 1 Araya R, Jiang J, Eisenthal KB, Yuste R (2006) The spine neck filters membrane potentials. PNAS. 103:17961-6 2 Araya R, Nikolenko V, Eisenthal KB, Yuste R. (2007) Sodium channels amplify spine potentials. PNAS 104(30):12347-52 3 Araya R, Eisenthal KB, Yuste R (2006b) Dendritic spines linearize the summation of excitatory potentials. PNAS. 103:18799-804 4 Arellano J, Benavides-Piccione R, DeFelipe J, Yuste R (2007) Ultrastructure of dendritic spines: correlation between synaptic and spine morphologies. Front. Neurosci. 1,1:131-143 5. Taylor AL, Hickey TJ, Prinz AA, Marder E (2006) Structure and visualization of high-dimensional conductance spaces. J Neurophysiol. 96(2):891-905