Odors are thought to be represented by a distributed code across the glomerular modules in the olfactory bulb (OB). Here, we optically imaged presynaptic activity in glomerular modules of the zebrafish OB induced by a class of natural odorants (amino acids [AAs]) after labeling of primary afferents with a calcium-sensitive dye. AAs induce complex combinatorial patterns of active glomerular modules that are unique for different stimuli and concentrations. Quantitative analysis shows that defined molecular features of stimuli are correlated with activity in spatially confined groups of glomerular modules. These results provide direct evidence that identity and concentration of odorants are encoded by glomerular activity patterns and reveal a coarse chemotopic organization of the array of glomerular modules.

Abstract. The intact sciatic nerve contains levels of nerve growth factor (NGF) that are comparable to those of densely innervated peripheral target tissues of NGF-responsive (sympathetic and sensory) neurons. There, the high NGF levels are reflected by correspondingly high mRNA N~F levels. In the intact sciatic nerve, mRNA N~F levels were very low, thus indicating that the contribution of locally synthesized NGF by nonneuronal cells is small. However, after transection an increase of up to 15-fold in mRNA NC~ was measured in 4-mm segments collected both proximally and distally to the transection site. Distally to the transection site, augmented mRNA N~F levels occurred in all three 4-mm segments from 6 h to 2 wk after transection, the longest time period investigated. The augmented local NGF synthesis after transection was accompanied by a reexpression of NGF receptors by Schwann cells (NGF receptors normally disappear shortly after birth). Proximal to the transection site, the augmented NGF synthesis was restricted to the very end of the nerve stump that acts as a "substitute target organ" for the regenerating NGF-responsive nerve fibers. While the mRNA NCF levels in the nerve stump correspond to those of a densely innervated peripheral organ, the volume is too small to fully replace the lacking supply from the periphery. This is reflected by the fact that in the more proximal part of the transected sciatic nerve, where mRNA N~F remained unchanged, the NGF levels reached only 40% of control values. In situ hybridization experiments demonstrated that after transection all nonneuronal cells express mRNA NCF and not only those ensheathing the nerve fibers of NGF-responsive neurons. N'ERVE growth factor (NGF)', a well-characterized protein, is essential for the embryonic development and the maintenance of specialized properties of the sympathetic and neural crest-derived sensory neurons (9,23,38). The similarity of the effects resulting from the administration of anti-NGF antibodies and the interference with the retrograde axonal transport provided indirect evidence for NGF to act as a retrograde messenger, transferring information from the peripheral target tissues to the innervating neurons (12, 33). More recently this indirect evidence has been corroborated by the demonstration that while the density of sympathetic innervation of target tissues is correlated with the levels of NGF (18) and its mRNA (14, 34), the high levels of NGF in both sympathetic and sensory ganglia are not reflected by correspondingly high levels of mRNA N~F (5, 14), implying that NGF is accumulated in the ganglia by axonal transport from the periphery rather than by local synthesis. This interpretation was supported by the observation that the destruction of sympathetic nerve terminals by 6-hydroxydopamine or blockade of axonal transport S. Korsching's present address is California Institute of Technology, Division of Biology, 216-76, Pasadena, California 91125.

The neurotrophic factor concept in its basic form envisages that innervated tissues produce a signal for the innervating neurons for the selective limitation of neuronal death occurring during development (Purves, 1986; Oppenheim, 1991). This concept arose several decades ago on the basis of the observation that experimental manipulation of the amount of target tissue could modulate the size of neuronal populations. By making the survival of neurons dependent on their target, nature would provide a means to match neuron and target cell populations. NGF, discovered in the 1950s, represents the first known molecular realization of the neurotrophic factor concept. NGF was found to regulate survival, neurite growth, and neurotransmitter production of a particular neuronal type, the sympathetic neurons of the PNS. NGF produced by target cells is specifically bound and internalized by sympathetic neurons, followed by retrograde axonal transport of NGF to the cell soma, where NGF exerts its effects via the cotransported receptor molecule (Levi-Montalcini, 1987; Thoenen et al., 1987). Strictly speaking, increased neurite growth and neurotransmitter production are not trophic effects; however, I will use the term "neurotrophic" in the extended meaning of enhancing neuronal differentiation as well as neuronal survival. It was expected that these results could be generalized to a model of multiple, mutually independent, retrograde trophic messengers, which are synthesized in distinct target areas and act on restricted neuronal types (Fig. 1). This assumption leads to a conceptually simple way to arrange and maintain a variety of neuronal subsystems. One might call this a modular approach to the construction of the nervous system. The hypothesis of multiple retrograde signals has gained widespread experimental support in recent years. Originally proposed for the PNS, the model could be extended to the CNS, in which target neurons synthesize trophic factors for their afferent neurons (Ernfors et al., 1990b). In addition to NGF, a family of NGF-related molecules (now commonly called neurotrophins), which are thought to exert retrograde trophic influences (DiStefano et al., 1992), has been identified.

The levels of nerve growth factor (NGF) and its mRNA in the rat central nervous system were determined by two‐site enzyme immunoassay and quantitative Northern blots, respectively. Relatively high NGF levels (0.4‐1.4 ng NGF/g wet weight) were found both in the regions innervated by the magnocellular cholinergic neurons of the basal forebrain (hippocampus, olfactory bulb, neocortex) and in the regions containing the cell bodies of these neurons (septum, nucleus of the diagonal band of Broca, nucleus basalis of Meynert). Comparatively low, but significant NGF levels (0.07‐0.21 ng NGF/g wet weight) were found in various other brain regions. mRNANGF was found in the hippocampus and cortex but not in the septum. This suggests that magnocellular cholinergic neurons of the basal forebrain are supplied with NGF via retrograde axonal transport from their fields of innervation. These results, taken together with those of previous studies showing that these neurons are responsive to NGF, support the concept that NGF acts as trophic factor for magnocellular cholinergic neurons.