, 2003). A pivotal issue, that has only recently begun to be addressed systematically, concerns the contribution of spine size and length to the charge produced at the synapse and recorded at the dendrite or soma. While theoretical assumption was that the spine was not a barrier to the transfer of the synaptic potential to the parent dendrite (Segev et al., 1995), experimental evidence for this issue is rather scarce, for the simple reason that such a comparison is difficult to obtain in view of the many different factors that contribute to the size of the synaptic current. However, tentative evidence suggests
that a shaft synapse makes a larger synaptic current recorded at the soma than a spine synapse. In our experiments (Fishbein & Segal, 2007), exposure of cultured cortical neurons to TTX for a period of 7–10 days caused dendritic spine pruning selleck inhibitor although synapses on the dendritic shafts were retained (Fig. 1).
In such cases miniature excitatory synaptic currents are nearly twice as large as those of controls. In a similar set of experiments (Segal et al., 2003), treatment of striatal–cortical cultures with TTX prevented the appearance of dendritic spines on striatal neurons, yet caused an almost two-fold increase in miniature excitatory postsynaptic current (mEPSC) amplitudes in these neurons compared to this website innervated control striatal–cortical cultures. Finally, transfection of cultured hippocampal neurons with DNA Damage inhibitor constitutively active Rho GTPase caused elimination of spines and shrinkage of dendrites, yet synapses were still present on dendrites of these neurons and they produced larger mEPSCs
than did controls (Pilpel & Segal, 2004). These experiments indicate that shaft synapses are likely to produce larger synaptic currents than spine synapses. In other series of experiments, we (Korkotian & Segal, 2007) and others (Araya et al., 2006) found that long spines produce smaller EPSCs evoked by local flash photolysis of caged glutamate than do short ones (Fig. 2). Similar studies also indicate that the spine neck may act as a barrier for the delivery of synaptic current from the synapse on the spine head to the parent dendrite (Ashby et al., 2006), which may explain the reduction in the synaptic current with distance from the spine head, and the observation that synapses on filopodia are less effective than spine synapses. A major impetus for the proposal that spines are the locus of synaptic plasticity originates in the early observations that spines constitute unique calcium compartments, able to raise [Ca2+]i levels locally to high concentrations that are not ‘seen’ in the parent dendrite and that such [Ca2+]i rises cannot be reached in an open-ended dendritic compartment. These high concentrations are probably needed for activation of calcium-dependent, plasticity-related kinases.