Fig. 2

Neuron versus synaptic maps of memory. The Golgi method used by Ramon y Cajal at the turn of the 19th century revealed that the brain consisted of individual nerve cells, leading to the formulation of the neuron doctrine. In modern neurobiology, expression of soluble fluorescent proteins allows visualization of individual neurons in the brain or, as shown here, in a hippocampal pyramidal neuron in dissociated culture (blue) (a). Identification of immediate early genes, such as cFos, provides a means of labeling the nuclei of individual neurons that are activated to undergo transcription following neuronal activity (violet) (b). This provides a neuron-level map of activity. However, each neuron forms thousands of synapses, shown in c by labeling a single neuron with presynaptic (green) and postsynaptic (red) markers (yellow where the pre- and post-synaptic elements are adjacent to one another). Note that this neuron is connected to other neurons in the culture that are not shown. Developing a synaptic rather than a neuron-wide map of memory requires obtaining activity-dependent markers that label the activated synapses rather than nuclei. Understanding synaptic maps will not only require understanding the identity of individual neurons but also the details of their cell-to-cell interactions