An emerging view of structure–function relations of synapses in central spiny neurons asserts that larger spines produce large synaptic currents and that these large spines are persistent (‘memory’) compared to small spines which are transient. Furthermore, ‘learning’ involves enlargement of small spine heads and their conversion to being large and stable. It is also assumed that the number of spines, hence the number of synapses, is reflected in the frequency of miniature excitatory postsynaptic currents (mEPSCs). Consequently, there is an assumption that the size and number of mEPSCs are closely correlated with, respectively, the physical size of synapses and number of spines. However, several recent observations do not conform to these generalizations, necessitating a reassessment of the model: spine dimension and synaptic responses are not always correlated. It is proposed that spines are formed and shaped by ongoing network activity, not necessarily by a ‘learning’ event, to the extent that, in the absence of such activity, new spines are not formed and existing ones disappear or convert into thin filopodia. In the absence of spines, neurons can still maintain synapses with afferent fibers, which can now terminate on its dendritic shaft. Shaft synapses are likely to produce larger synaptic currents than spine synapses. Following loss of their spines, neurons are less able to cope with the large synaptic inputs impinging on their dendritic shafts, and these inputs may lead to their eventual death. Thus, dendritic spines protect neurons from synaptic activity-induced rises in intracellular calcium concentrations.