The olfactory bulb in vertebrates lies at the very front of the brain, and is responsible for processing information from olfactory receptors in the nose. The bulb has two parts, the ‘’main olfactory bulb’’ and the ‘’accessory olfactory bulb’’. Nerve fibres from the vomeronasal organ (Jacobson’s organ), a chemosensitive organ at the base of the nasal cavity, innervate the accessory olfactory bulb whereas the olfactory nerves terminate in the main olfactory bulb. The cellular architecture and synaptic organisation are similar in the two parts of the bulb, but the laminar organisation in the accessory olfactory bulb is less distinct. The output from the olfactory bulb is carried by the axons of the "principal neurones", the mitral and tufted cells, in the lateral olfactory tract.
Inputs to the olfactory bulb
The olfactory sensory neurones are bipolar cells; each has a dendrite that extends to the mucosal surface where it gives rise to cilia that allow odours to interact with the cell, and an axon that projects to the olfactory bulb. There is a large gene family that encodes for seven transmembrane domain receptor proteins, whose expression is restricted to the olfactory epithelium; these encode individual odorant receptors. Individual sensory neurones express one or a few types of these receptors.
The main olfactory bulb has five distinct layers (laminae). The axons of the olfactory nerve terminate exclusively in the glomeruli.
- The glomerular layer is comprised of the olfactory glomeruli, large spherical structures up to 0.2 mm or more in diameter, surrounded by glial sheaths that separate them from surrounding neuronal somata. The glomeruli contain no neuronal cell bodies, they mainly consist of olfactory nerve terminals and the dendrites of the principal neurones (mitral/tufted cells) and interneurones (periglomerular and short-axon cells). No cells in the granule cell layer send dendrites into the glomeruli. There is a huge convergence of axons onto individual glomeruli. Inside the glomeruli the olfactory nerve terminals make axodendritic synapses onto the dendrites of the mitral and tufted cells and the periglomerular cells. Activity in one glomerulus can affect other glomeruli through interglomerular connections via the periglomerular cells.
- The external plexiform layer consists mainly of mitral cell primary dendrites that are coursing upward toward the glomeruli and many lateral dendrites belonging to both mitral/tufted cells and granule cells. The mitral cells have branching, lateral dendrites that can be 0.8-1 mm long; they are orientated horizontally to the axis of the primary dendrite, and end within the external plexiform layer. The dominant type of synaptic interaction is a pair of reciprocal contacts between the secondary dendrite of a mitral/tufted cell and the spine of a granule cell dendrite. In the reciprocal pair, the mitral-to-granule synapse is Type 1 (excitatory) whereas, the granule-to-mitral synapse is Type 2 (inhibitory). Over 80% of the synapses in the external plexiform layer are involved in such reciprocal pairs. At the level of output control in this layer, each type of principal neurone is dominated by different subpopulations of granule cells: superficial granule cells control superficial and middle tufted cells, and deep granule cells control mitral cells. As well as synapses made by the dendrites, the external plexiform layer also contains axon terminals from intrinsic short axon cells and centrifugal fibres (from the locus coeruleus and horizontal limb of the diagonal band of Broca). These terminals make Type 1 synapses mainly onto the granule cells.
- The mitral cell layer is a narrow band (2-3 cells wide) of mitral cell bodies. Each mitral cell sends its primary dendrite to the glomerular layer where it forms a tuft within the glomerulus and synapses with the primary olfactory nerve axons. The mitral cell also has secondary dendrites within the external plexiform layer that can reach lengths of 0.4-0.5 mm, travelling almost the circumference of the bulb. Mitral cells are the largest neurones in the bulb; they are up to 0.3 mm in diameter and have a characteristic pyramidal shape. The primary dendrite is directed radially outwards towards the glomeruli. Each mitral cell also has several secondary dendrites; these are laterally directed and terminate in the external plexiform layer. The primary and secondary dendrites have generally smooth surfaces, thus mitral cells are "aspiny" neurones. The mitral cell axons proceed deep into the olfactory bulb, through the granule cell layer, and pass caudally to gather at the posterolateral surface to form the lateral olfactory tract (LOT). The fibres from the accessory olfactory bulb collect into the accessory olfactory tract, which runs with the LOT. The secondary dendrites of mitral cells extend across large regions of the olfactory bulb and the influence of a single mitral cell may extend further, as single granule cells contact many mitral cells. This may be the anatomical substrate for lateral inhibition within the olfactory bulb, which is believed to play an important role in odour discrimination.
- Between the mitral cell layer and the granule cell layer is a narrow layer relatively free of cell bodies - the internal plexiform layer - which mainly consists of granule cell dendrites passing through on their way to the EPL. Some axons and dendritic processes of short-axon cells and terminations of centrifugal fibres are also found in this region. The external tufted cells send their axons into the internal plexiform layer, where they form a dense tract and travel within this layer to the opposite side of the bulb where they terminate on the apical branches of granule cells. Hence the activity on one side of the bulb can influence the activity on the opposite side.
- The granule cell layer contains the cell bodies of many interneurones: the granule cells and the short-axon cells. Axon terminals are found on both the shafts and spines of the granule cell dendrites; these derive from both intrinsic (axon collaterals of mitral/tufted cells and the axons of deep short-axon cells) and centrifugal inputs. Fibres from the pars medialis of the anterior olfactory nucleus terminate in the deep half of the granule cell layer; while the pars posterior, ventralis, dorsalis and lateralis of the anterior olfactory nucleus terminate in the superficial granule cell layer.
The output of the accessory olfactory bulb is to the medial anterior, medial posterior, and posterior cortical nuclei of the amygdala. These amygdaloid nuclei project to the medial preoptic area and the medial hypothalamus, which are involved in regulating reproduction and aggression. These pathways are thought to be involved in the perception of chemical stimuli of a social nature, stimuli which can induce hormonal changes, affect the success of pregnancy, alter the course of puberty, modulate female cyclicity and ovulation, and elicit courtship behaviour.
By contrast, the main olfactory bulb projects the anterior cortical and posterolateral cortical nuclei of the amygdala. Efferents from these parts of the amygdala project to the mediobasal hypothalamus and the bed nucleus of the stria terminalis via the stria terminalis. The main olfactory bulb also projects to the amygdalo-hippocampal area and the primary olfactory cortex The olfactory cortex has relatively little radial or columnar organisation and relies on its associational areas, a collection of structures including the piriform cortex, the anterior olfactory nucleus, the entorhinal cortex, the infralimbic cortex and the olfactory tubercle, for processing olfactory information.
The olfactory bulb is under extensive control by the brain. Extensive connections are made by fibres from the anterior olfactory nucleus, and also by axon collaterals from pyramidal neurones in the olfactory cortex, all of which terminate within the granule cell layer. Axons from the rostral regions of the piriform cortex terminate on the superficial layer of granule cells, whereas more caudal regions send afferents to the deep portion of the granule cell layer. Centrifugal afferents also arise from the nucleus of the horizontal limb of the diagonal band; the locus coeruleus and the raphe nucleus all of which terminate within both the granule cell layer and the periglomerular regions of the glomerular layer.
In addition, mitral/tufted cells project to the pars externa of the anterior olfactory nucleus, whose cells project via the anterior commisure to a region of the contralateral bulb homotopic to the region of the ipsilateral bulb from which they received their input. Corresponding regions of the two bulbs can thus influence each other. Activation of the commissural pathways by electrical stimulation of the anterior olfactory nucleus or the contralateral olfactory bulb produces strong inhibition of mitral/tufted cells, mediated through granule cells. A second bilateral pathway involves olfactory information being transferred to the contralateral hemisphere at the level of the piriform cortex.
Output cells like mitral cells, but which are distributed throughout the external plexiform layer, are called "tufted cells". The tufted cells are a heterogeneous group, classified into subsets according to the location of their somata. The main population, middle tufted cells, lie in the middle of the external plexiform layer and are slightly smaller than mitral cells. The primary dendrite terminates as a "tuft" of branches in a glomerulus, and the axon collaterals are mostly confined within the internal plexiform layer and granule cell layer. Many of their axons join the LOT but have different projection patterns to the central olfactory areas than mitral cells. External tufted cells are found in the glomerular layer and have the shortest secondary dendrites; the length of the secondary dendrites increases progressively with the depth of the cell body in the external plexiform layer. External tufted cells give rise to extensive axon collaterals in the internal plexiform and granule cell layers; some send an axon into the LOT, whereas others are intrinsic neurones. The internal tufted cells have cell bodies in the deep external plexiform layer close to the border with the mitral cell layer.
Intrinsic neurones of the olfactory bulb
The periglomerular cells are mostly found at the deep border of the glomerular layer, surrounding the glomeruli. These have small cell bodies (8-10m in diameter) and send a dendritic tuft into one (sometimes two) glomeruli. The dendritic branches intermingle with the terminals of olfactory axons and the branches of mitral and tufted cells. The branching axons of periglomerular cells course laterally and end in or near neighbouring glomeruli.
Granule cells are small (0.08-0.1 mm in diameter) and are by far the most numerous cell type in the bulb. The cell bodies lie in sheets below the internal plexiform layer and their dendrites radiate upwards and ramify in the external plexiform layer, but do not enter the glomeruli. There is also a deep process that branches sparingly in the granule cell layer. A characteristic feature of granule cells is the spines that cover the dendritic processes. Gap junctions are found between adjacent cell bodies in the granule cell layer, indicating that they are electrically coupled.
Terminations of the projections, running through the anterior commisure from the pars externa, are found in the superficial layers of the granule cell layer in the contralateral bulb. However, the projections from medial and ventral parts of the anterior olfactory nucleus end both in the deep zone of the granule layer and in the glomerular layer. This segregation of extrinsic inputs to the granule cells is consistent with the idea that distinct populations of granule cells are involved in local circuits and output pathways, working in parallel with each other.
Short-axon cells Short-axon cells are a diverse group found throughout the granule, periglomerular and external plexiform layers. They do not receive olfactory nerve inputs nor do they make synaptic contact with mitral/tufted dendrites, although they may receive some mitral/tufted axon synapses; they are involved primarily in interglomerular communication. Short-axon cell dendrites are contacted by the axons of periglomerular cells and they in turn, send axons to contact the extraglomerular dendrites of adjacent periglomerular cells. Short-axon cells are also connected axodendritically with other short axon cells. The axons of superficial short-axon cells can reach all levels of the external plexiform layer as well as the periglomerular region.
All of the synaptic connections in which the granule cell takes part are orientated toward the granule cell, with the sole exception of the dendrodendritic synapses from the granule spines onto the mitral dendrites in the external plexiform layer. The latter are therefore the only outputs from the granule cell.