1962). Indeed, the two membranes are separated by a Calcium plays an important role in regulating a great fuzzy material with a distinct periodicity reminiscent of variety of neuronal processes. Like other cells, neurons the triadic junction of muscle cells (Henkart et al., 1976). use both extracellular and intracellular sources of cal-In the axonal initial segment of certain neurons (eg, cium. The mechanisms responsible for regulating the cortical principal cells, spiny stellate cells, and dentate influx of external calcium are well established (Figure granule cells) the subsurface cisternae appear as multi-1). For example, voltage-operated channels are used layered structures called cisternal organelles (Peters et to trigger the release of neurotransmitter at synaptic al., 1968; Kosaka, 1980; Takei et al., 1992; Benedeczky junctions and they contribute to dendritic action potenet al., 1994). In the case of the initial segment of CA3 tials. In addition, neurotransmitters can induce an influx hippocampal neurons, both subsurface cisternae and cisof calcium using receptor-operated channels such as ternal organelles coexist (Kosaka, 1980). These subsurthe NMDA receptors located primarily at postsynaptic face cisternae and cisternal organs may play an imporsites. While much is known about these influx pathways, tant role in regulating neuronal excitability (see below). there is less information on the mechanism and role Within the axon, the endoplasmic reticulum consists of the intracellular supply of calcium stored within the of connecting tubules running parallel with the axon endoplasmic reticulum of neurons. Inositol 1, 4, 5-tris-(Droz et al., 1975; Broadwell and Cataldo, 1984; Lindsay phosphate receptors (InsP3Rs) or ryanodine receptors and Ellisman, 1985). Occasionally the tubules connect (RYRs) distributed throughout the endoplasmic reticu- to hypolemmal cisternae, which are flattened sheets that lum are responsible for releasing Ca2+ from this internal lie close to the plasma membrane and thus resemble store (Figure 1). Since the endoplasmic reticulum is a the subsurface cisternae. This axonal endoplasmic recontinuous network distributed throughout the cell, it ticulum network extends into the synapse where it is may be considered as a neuron-within-a-neuron, a con- often closely associated with a mitochondrion (Bird, cept that becomes all the more interesting because the 1978; McGraw et al., 1980; Westrum and Gray, 1986). endoplasmic reticulum, like the plasma membrane, has At the opposite end of the cell, the endoplasmic reticuboth integrative and regenerative properties that could lum network extends throughout the dendritic tree and into the spines, where it finally terminates as the spine play important roles in neural signaling. This review exapparatus (Figure 2)(Harris and Stevens, 1988; Mignery plores the idea that the endoplasmic reticulum and the et al., 1989; Satoh et al., 1990; Martone et al., 1993; plasmamembrane forma binary membrane systemthat Spacek and Harris, 1997). As indicated by Spacek and functions to regulate a variety of neuronal processes Harris (1997), 50% of the spines contain a spine appaincluding excitability, associativity, neurotransmitter reratus. The latter consists of closely stacked plates of lease, synaptic plasticity, and gene transcription. endoplasmic reticulum separated by a densely staining material. The important point to stress is that the den-