Consistent with this, voltage-gated conductances can be differentially activated in the spine and the dendritic shaft, something that should not occur if both compartments are isopotential (Araya et al., 2007 and Bloodgood et al., 2009). Also, under synaptic stimulation, some spines apparently sustain substantially higher voltages than their neighboring dendritic shafts (Palmer and Stuart, 2009). These results indicate that the spine may not be isopotential with its

parent dendrite. The simplest explanation for this is that the spine neck resistance must be high enough to filter membrane potential and cause this electrical compartmentalization. Indeed, uncaging glutamate experiments, activating one spine at compound screening assay a time, reveal an inverse relation between selleck kinase inhibitor the spine neck length and the amplitude of the uncaging potential, when measured at the soma (Araya et al., 2006b). These results indicate that the spine

neck could significantly attenuate the membrane potential as it passes to the dendritic shaft. The exact mechanisms behind this filtering, whether it is due to passive features of the electrical structure of the spine neck (like physical constrictions, clogging by small organelles or abnormal flow of current), or to active conductances, such as potassium channels, in the spine neck membrane, remain unknown. Attenuating a synaptic

potential makes little functional sense: why would a neuron diminish the amplitude of a synaptic signal it has worked so hard to generate? As suggested, filtering synaptic potentials would electrically isolate inputs from one another, preventing their interaction and preserving their independent integration. This would occur by reducing the average effective conductance of each input and by making synapses current-injecting devices. Both mechanisms could help generate a linear input integration regime (Jack et al., 1975, Llinás and Hillman, 1969 and Rall, 1974b; Rall and Rinzel, 1971). If this is the case, linear integration because must be so important that a neuron is willing to pay the price of reducing synaptic voltages to maintain it. But is input integration actually linear? Indeed, in pyramidal neurons, when several excitatory inputs, or several dendritic spines, are stimulated simultaneously, one observes a linear summation of their potentials, even when inputs are in close proximity to each other (Araya et al., 2006a, Cash and Yuste, 1998 and Cash and Yuste, 1999). Similar results have been reported among inputs from connected pairs of excitatory neurons (A.D. Reyes and B. Sakmann, 1996, Soc. Neurosci. Abstr. 22, 792). In experiments when inputs were activated with various delays, linear integration in time was also found ( Cash and Yuste, 1999).