8 Cohen and pfaff Fig4Electron micrograph of a hypothalamic neuron actively Fig. 5. Electron micrograph of a Golgi apparatus of a teins. Many cisternae of rough endoplasmic reticulum(er) apparatus on all sides. The cis face is located near the rough and associated dense-cored vesicles(arrowheads)are also visi- the trans Golgi network(TGN). Secretory material is detected ble(From Cohen RS. Pfaff Dw. Ultrastructure of neurons in within the peripheral portions of the cisternae(arrowheads)of he ventromedial nucleus of the hypothalamus with or without the tgN. a dense-cored vesicle(arrow)containing material of estrogen treatment. Cell Tissue Res 1981: 217: 463. similar density is seen at the periphery of the TGN reticulum vary and appear to depend on the prevail- The secretory material is later detected within the ing demands for secretory protein synthesis in a cisternae occupying the trans-Golgi network. Often, functional group of neurons In nerve cells that are at the periphery of the sacs, the membranes appear to quiescent in regard to the production of exportable constrict around a dense granule, which is the con proteins, cisternae of the rough endoplasmic reticu- centrated precursor protein(Fig. 5). The granule- lum appear as discrete sacs and seem to occupy only a containing membranous compartment is pinched small fraction of the cellular space. Neurons actively off, forming a dense-cored vesicle. Although the engaged in secretory protein synthesis contain large details of protein processing within the Golgi appa stacks of elongated cisternae that fill a considerable ratus have not yet been elucidated, its overall function portion of the perikaryon. is known: the preparation and packaging of the secre- 2.2.1.2. Packaging and Modification ot Exporta- to the axon terminal for storage or release<ransport tory protein, still in its precursor form, fo ble Neuropeptides in the Golgi Apparatus. The Golgi apparatus is composed of a series of flattened, smooth-surfaced, membranous sacs and a variety of 2.2.1.3. Formation of the Active Neuropeptide associated small vesicles, which encompass the Golgi Within the Neurosecretory Vesicle. The actual apparatus on all sides(Fig. 5). The Golgi cisternae enzymatic processing of the precursor and generation are arranged in a polarized fashion, reflecting their of individual biologically active peptides appear to morphology and function. The forming or cis face occur distal to the golgi apparatus as the secretory approaches the rough endoplasmic reticulum; the vesicle makes its way down the axon. Conditions, opposite side is designated as the maturing or trans such as pH, necessary for the maximal activity of face or trans-Golgi network. Vesicles bud off from the processing enzymes, are optimal. The relatively the smooth transitional portion of the rough endo- simple structure of the secretory vesicle-a dense core plasmic reticulum and transport their contents to surrounded by a single membrane-belies its dynamic Golgi sacs on the cis face. Here, they deliver the role in generating active neuropeptides. Various enzy- newly synthesized precursor protein by fusion of matic activities have been located in neurosecretory the vesicle membrane with the Golgi membrane. vesicles, and some have been purified and characterizedreticulum vary and appear to depend on the prevail￾ing demands for secretory protein synthesis in a functional group of neurons. In nerve cells that are quiescent in regard to the production of exportable proteins, cisternae of the rough endoplasmic reticu￾lum appear as discrete sacs and seem to occupy only a small fraction of the cellular space. Neurons actively engaged in secretory protein synthesis contain large stacks of elongated cisternae that fill a considerable portion of the perikaryon. 2.2.1.2. Packaging and Modification of Exporta￾ble Neuropeptides in the Golgi Apparatus. The Golgi apparatus is composed of a series of flattened, smooth-surfaced, membranous sacs and a variety of associated small vesicles, which encompass the Golgi apparatus on all sides (Fig. 5). The Golgi cisternae are arranged in a polarized fashion, reflecting their morphology and function. The forming or cis face approaches the rough endoplasmic reticulum; the opposite side is designated as the maturing or trans face or trans-Golgi network. Vesicles bud off from the smooth transitional portion of the rough endo￾plasmic reticulum and transport their contents to Golgi sacs on the cis face. Here, they deliver the newly synthesized precursor protein by fusion of the vesicle membrane with the Golgi membrane. The secretory material is later detected within the cisternae occupying the trans-Golgi network. Often, at the periphery of the sacs, the membranes appear to constrict around a dense granule, which is the con￾centrated precursor protein (Fig. 5). The granule￾containing membranous compartment is pinched off, forming a dense-cored vesicle. Although the details of protein processing within the Golgi appa￾ratus have not yet been elucidated, its overall function is known: the preparation and packaging of the secre￾tory protein, still in its precursor form, for transport to the axon terminal for storage or release. 2.2.1.3. Formation of the Active Neuropeptide Within the Neurosecretory Vesicle. The actual enzymatic processing of the precursor and generation of individual biologically active peptides appear to occur distal to the Golgi apparatus as the secretory vesicle makes its way down the axon. Conditions, such as pH, necessary for the maximal activity of the processing enzymes, are optimal. The relatively simple structure of the secretory vesicle—a dense core surrounded by a single membrane—belies its dynamic role in generating active neuropeptides. Various enzy￾matic activities have been located in neurosecretory vesicles, and some have been purified and characterized. Fig. 4. Electron micrograph of a hypothalamic neuron actively engaged in the synthesis and packaging of exportable pro￾teins. Many cisternae of rough endoplasmic reticulum (er) are arranged in parallel stacks. The Golgi apparatus (GA) and associated dense-cored vesicles (arrowheads) are also visi￾ble. (From Cohen RS, Pfaff DW. Ultrastructure of neurons in the ventromedial nucleus of the hypothalamus with or without estrogen treatment. Cell Tissue Res 1981;217:463.) Fig. 5. Electron micrograph of a Golgi apparatus of a hypothalamic neuron. Small vesicles surround the Golgi apparatus on all sides. The cis face is located near the rough endoplasmic reticulum (er); the opposite side is designated as the trans Golgi network (TGN). Secretory material is detected within the peripheral portions of the cisternae (arrowheads) of the TGN. A dense-cored vesicle (arrow) containing material of similar density is seen at the periphery of the TGN. 8 Cohen and Pfaff