**3. The glomerulus in olfaction**

The structural unit of organization in the AL or OB is the glomerulus [24, 31–37], that is, the neuropil is arranged into discrete areas ensheathed by a glial envelope [38, 39]. In *M. sexta*, glial cells play an important role in the sculpturing of glomeruli, since early removal of glial cells results in an absence of these subunits [38]. Glomeruli are the sites of synaptic interaction between primary olfactory axons and dendritic arborizations of central olfactory neurons [40]. Unlike that observed in vertebrates, evidence for moths and cockroaches suggests that in insects, few or no synaptic interactions take place in the neuropil outside the glomeruli [41, 42].

The brain and nervous system can be considered as arrangements of modular structures. Glomeruli are a prime example of such modular structures that are repeated in a specific brain region. It was Camillo Golgi (1874, cited in [34]) who first noted glomeruli. Since his early discovery, other modular structures have been described. Examples include columns, barrels, barreloids, and blobs [33, 34]. Considerable variation has been described for these modular structures in different species. In closely related species, one of them can lacks such an iterated module of brain organization but still achieves the same behavioral functions as the species that has them [34].

Glomeruli have also been found in the cerebellar cortex and the thalamic regions of vertebrates [25, 43]. Olfactory glomeruli have a long evolutionary history as they have been described in phylogenetically old animal groups. These groups include marine crustacea, fishes, onychophora, myriapoda, and mollusca. Glomeruli appeared before animals transitioned from marine to terrestrial life forms [25].

Glomeruli are not only structural modules but also functional units [33, 44]. 2-deoxyglucose (2-DG) studies in neonatal rat pups established a focal point in the dorsal part of the olfactory bulb, the modified glomerular complex. This is a small group of glomeruli involved in processing of suckling odor cues. In *Drosophila melanogaster*, 2-DG mapping of odor-induced neuronal activity in the ALs labeled distinct and histologically identified glomeruli [45, 46]. In insects, the macroglomerular complex has been established as the first central site where information about the female sex pheromone is processed [6, 47]. During odor stimulation of the rat olfactory epithelium, neighboring mitral/tufted cells, that is, the output neurons of the olfactory bulb that innervate the same glomerulus in the olfactory bulb, were frequently simultaneously excited or inhibited compared to cells that innervated different glomeruli [48].

The existing data indicates that glomeruli are functional units such that information about odorants is represented in a spatial manner among glomeruli. When the olfactory epithelium is stimulated with most odorants, the resulting responses in the AL or olfactory bulb are spatial gradients or patterns of activity in more than one glomerulus [23, 45, 46, 49–51]. Three measures of neural activation (voltage-sensitive dyes, the 2-DG method, and *c-fos* expression) have revealed that in mammals, different odors elicit overlapping but distinctly different patterns of glomerular activity [51–54]. In the cockroach *Periplaneta americana*, stimulation with the female sex pheromone evokes responses in a very limited number of neurons and glomeruli, whereas general odorants result in responses in different output neurons representing more than 10 out of 130 glomeruli [55]. In *D. melanogaster*, stimulation with complex odors as well as with individual odors results in a spatial pattern of 2-DG activity in different specific subsets of antennal lobe glomeruli [45, 46].

A synthesis of the diffuse as well as specific aspects of the primary olfactory projections to central sites came from Ken Mori et al. [56, 57]. They characterized individual mitral/tufted cells based on the range of odor molecules effective in activating each cell. Individual mitral/tufted cells showed excitatory responses to groups of molecules with similar chemical structure [57]. Imamura et al. [56] developed a model for the activation of individual mitral/tufted cells by a range of odor molecules. In the model that takes into account work in different research groups, an olfactory sensory neuron expresses one or, at most, a few different types of receptor proteins. Subsequently, a neuron is activated by odor molecules with similar structure. The olfactory pathway is thought to work with a one cell-one receptor rule [58] such that a sensory cell expresses only one among hundreds of possible molecular receptors [59]. Neurons with the same or similar receptor proteins send one axon each to one or a few glomeruli and thus define glomerular function [60, 61]. The tuning specificity of the mitral/tufted cells thus reflects the specificity of the receptor protein [54, 56]. Recent studies have indicated that individual receptor probes hybridize to a small number of olfactory glomeruli. This suggests that axons of sensory neurons expressing the same olfactory receptor protein converge on only a small number of glomeruli [60, 61]. Together with the notion that individual mitral/tufted cells arborizing in single glomeruli have similar response specificities, the resulting picture is that each glomerulus appears to have a unique mixture of inputs [52]. This input, in turn, limits its odor specificity, also known as its molecular receptive range.
