The olfactory bulb (

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

: ''bulbus olfactorius'') is a neural structure of the

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...

forebrain In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hindbrain (rhombencephalon) are the three primary ...

involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the

orbitofrontal cortex The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 1 ...

(OFC) and the

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

where it plays a role in emotion, memory and learning. The bulb is divided into two distinct structures: the main olfactory bulb and the accessory olfactory bulb. The main olfactory bulb connects to the amygdala via the

piriform cortex The piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell. Structure The piriform cortex is part of the rhinencepha ...

of the

primary olfactory cortex The primary olfactory cortex (POC) is a portion of the cerebral cortex. It is found in the inferior part of the temporal lobe of the brain. It receives input from the olfactory tract. It is involved in the sense of smell (olfaction). Structure ...

and directly projects from the main olfactory bulb to specific amygdala areas. The accessory olfactory bulb resides on the dorsal-posterior region of the main olfactory bulb and forms a parallel pathway. Destruction of the olfactory bulb results in

ipsilateral Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a nu ...

, while irritative lesions of the uncus can result in olfactory and

gustatory The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

hallucinations. Early Olfactory System

Structure

In most vertebrates, the olfactory bulb is the most rostral (forward) part of the brain, as seen in rats. In humans, however, the olfactory bulb is on the inferior (bottom) side of the brain. The olfactory bulb is supported and protected by the

cribriform plate In mammalian anatomy, the cribriform plate (Latin for lit. ''sieve-shaped''), horizontal lamina or lamina cribrosa is part of the ethmoid bone. It is received into the ethmoidal notch of the frontal bone and roofs in the nasal cavities. It supp ...

of the ethmoid bone, which in mammals separates it from the

olfactory epithelium The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, it measures 9 cm2 and lies on the roof of the nasal cavity about 7 cm above and behind the nostrils. The olfactory ...

, and which is perforated by olfactory nerve axons. The bulb is divided into two distinct structures: the main olfactory bulb and the accessory olfactory bulb.

Layers

The main olfactory bulb has a multi-layered cellular architecture. In order from surface to the center the layers are: * Glomerular layer *External plexiform layer *

Mitral cell Mitral cells are neurons that are part of the olfactory system. They are located in the olfactory bulb in the mammalian central nervous system. They receive information from the axons of olfactory receptor neurons, forming synapses in neuropils ca ...

layer *Internal plexiform layer *Granule cell layer The olfactory bulb transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell. As a neural circuit, the glomerular layer receives direct input from

afferent nerves A sensory nerve, or afferent nerve, is a general anatomic term for a nerve which contains predominantly somatic afferent nerve fibers. Afferent nerve fibers in a sensory nerve carry sensory information toward the central nervous system (CNS) from ...

, made up of the axons from approximately ten million olfactory receptor neurons in the olfactory mucosa, a region of the nasal cavity. The ends of the axons cluster in spherical structures known as

glomeruli ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...

such that each glomerulus receives input primarily from olfactory receptor neurons that express the same

olfactory receptor Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give r ...

. The glomeruli layer of the olfactory bulb is the first level of synaptic processing. The glomeruli layer represents a spatial odor map organized by chemical structure of odorants like functional group and carbon chain length. This spatial map is divided into zones and clusters, which represent similar glomeruli and therefore similar odors. One cluster in particular is associated with rank, spoiled smells which are represented by certain chemical characteristics. This classification may be evolutionary to help identify food that is no longer good to eat. The spatial map of the glomeruli layer may be used for perception of odor in the olfactory cortex. The next level of synaptic processing in the olfactory bulb occurs in the external plexiform layer, between the glomerular layer and the mitral cell layer. The external plexiform layer contains astrocytes,

interneurons Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...

and some mitral cells. It does not contain many cell bodies, rather mostly

dendrites Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the ...

of mitral cells and GABAergic granule cells are also permeated by dendrites from neurons called

mitral cell Mitral cells are neurons that are part of the olfactory system. They are located in the olfactory bulb in the mammalian central nervous system. They receive information from the axons of olfactory receptor neurons, forming synapses in neuropils ca ...

s, which in turn output to the olfactory cortex. Numerous interneuron types exist in the olfactory bulb including periglomerular cells which synapse within and between glomeruli, and granule cells which synapse with mitral cells. The granule cell layer is the deepest layer in the olfactory bulb. It is made up of dendrodendritic granule cells that synapse to the mitral cell layer.

Function

This part of the brain receives sensations of smell. As a neural circuit, the olfactory bulb has one source of sensory input (axons from olfactory receptor neurons of the olfactory epithelium), and one output (mitral cell axons). As a result, it is generally assumed that it functions as a

filter Filter, filtering or filters may refer to: Science and technology Computing * Filter (higher-order function), in functional programming * Filter (software), a computer program to process a data stream * Filter (video), a software component tha ...

, as opposed to an associative circuit that has many inputs and many outputs. However, the olfactory bulb also receives "top-down" information from such brain areas as the olfactory cortex, amygdala, neocortex,

, locus coeruleus, and substantia nigra. Its potential functions can be placed into four non-exclusive categories: *discriminating among odors *enhancing sensitivity of odor detection *filtering out many background odors to enhance the transmission of a few select odors *permitting higher brain areas involved in arousal and attention to modify the detection or the discrimination of odors. While all of these functions could theoretically arise from the olfactory bulb's circuit layout, it is unclear which, if any, of these functions are performed exclusively by the olfactory bulb. By analogy to similar parts of the brain such as the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

, many researchers have focused on how the olfactory bulb filters incoming information from receptor neurons in space, or how it filters incoming information in time. At the core of these proposed filters are the two classes of interneurons; the periglomerular cells, and the granule cells. Processing occurs at each level of the main olfactory bulb, beginning with the spatial maps that categorize odors in the glomeruli layer. Interneurons in the external plexiform layer are responsive to pre-synaptic action potentials and exhibit both excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Neural firing varies temporally, there are periods of fast, spontaneous firing and slow modulation of firing. These patterns may be related to sniffing or change in intensity and concentration of odorant. Temporal patterns may have effect in later processing of spatial awareness of odorant. For example, synchronized mitral cell spike trains appear to help to discriminate similar odors better than when those spike trains are not synchronized. A well known model is that the bulbar neural circuit transforms the odor information in the receptors to a population pattern of neural oscillatory activities in the mitral cell population, and this pattern is then recognized by the associative memories of olfactory objects in the olfactory cortex. Top-down feedback from the olfactory cortex to the olfactory bulb modulates the bulbar responses, so that, for example, the bulb can adapt to a pre-existing olfactory background to single out a foreground odor from an odor mixture for recognition, or can enhance sensitivity to a target odor during odor search. Destruction to the olfactory bulb results in

while irritative lesion of the uncus can result in olfactory and

hallucinations.

Lateral inhibition

;External plexiform layer The interneurons in the external plexiform layer perform feedback inhibition on the mitral cells to control back propagation. They also participate in

lateral inhibition In neurobiology, lateral inhibition is the capacity of an excited neuron to reduce the activity of its neighbors. Lateral inhibition disables the spreading of action potentials from excited neurons to neighboring neurons in the lateral direction ...

of the mitral cells. This inhibition is an important part of olfaction as it aids in odor discrimination by decreasing firing in response to background odors and differentiating the responses of olfactory nerve inputs in the mitral cell layer. Inhibition of the mitral cell layer by the other layers contributes to odor discrimination and higher level processing by modulating the output from the olfactory bulb. These hyperpolarizations during odor stimulation shape the responses of the mitral cells to make them more specific to an odor. There is a lack of information regarding the function of the internal plexiform layer which lies between the mitral cell layer and the granule cell layer. ;Granule cell layer The basal

of mitral cells are connected to interneurons known as granule cells, which by some theories produce

between mitral cells. The synapse between mitral and granule cells is of a rare class of synapses that are "dendro-dendritic" which means that both sides of the synapse are dendrites that release neurotransmitter. In this specific case, mitral cells release the excitatory neurotransmitter glutamate, and granule cells release the inhibitory neurotransmitter Gamma-aminobutyric acid (GABA). As a result of its bi-directionality, the dendro-dendritic synapse can cause mitral cells to inhibit themselves (auto-inhibition), as well as neighboring mitral cells (lateral inhibition). More specifically, the granule cell layer receives excitatory glutamate signals from the basal dendrites of the mitral and tufted cells. The granule cell in turn releases GABA to cause an inhibitory effect on the mitral cell. More neurotransmitter is released from the activated mitral cell to the connected dendrite of the granule cell, making the inhibitory effect from the granule cell to the activated mitral cell stronger than the surrounding mitral cells. It is not clear what the functional role of lateral inhibition would be, though it may be involved in boosting the signal-to-noise ratio of odor signals by silencing the basal firing rate of surrounding non-activated neurons. This in turn aids in odor discrimination. Other research suggest that the lateral inhibition contributes to differentiated odor responses, which aids in the processing and perception of distinct odors. There is also evidence of cholinergic effects on granule cells that enhance depolarization of granule cells making them more excitable which in turn increases inhibition of mitral cells. This may contribute to a more specific output from the olfactory bulb that would closer resemble the glomerular odor map. Olfaction is distinct from the other

sensory system The sensory nervous system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory neurons (including the sensory receptor cells), neural pathways, and parts of the brain involved i ...

s where peripheral sensory receptors have a relay in the diencephalon. Therefore, the olfactory bulb plays this role for the

olfactory system The olfactory system, or sense of smell, is the sensory system used for smelling ( olfaction). Olfaction is one of the special senses, that have directly associated specific organs. Most mammals and reptiles have a main olfactory system and an ...

Accessory olfactory bulb

In vertebrates, the accessory olfactory bulb (AOB), which resides on the dorsal-posterior region of the main olfactory bulb, forms a parallel pathway independent from the main olfactory bulb. The vomeronasal organ sends projections to the accessory olfactory bulb making it the second processing stage of the accessory olfactory system. As in the main olfactory bulb, axonal input to the accessory olfactory bulb forms synapses with mitral cells within glomeruli. The accessory olfactory bulb receives axonal input from the vomeronasal organ, a distinct sensory epithelium from the main

that detects chemical stimuli relevant for social and reproductive behaviors, but probably also generic odorants. It has been hypothesized that, in order for the vomernasal pump to turn on, the main olfactory epithelium must first detect the appropriate odor. However, the possibility that the vomeronasal system works in parallel or independently from generic olfactory inputs has not been ruled out yet. Vomeronasal sensory neurons provide direct excitatory inputs to AOB principle neurons called mitral cells which are transmitted to the amygdala and

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

and therefore are directly involved in sex hormone activity and may influence aggressiveness and mating behavior. Axons of the vomeronasal sensory neurons express a given receptor type which, differently from what occurs in the main olfactory bulb, diverge between 6 and 30 AOB glomeruli. Mitral cell dendritic endings go through a dramatic period of targeting and clustering just after presynaptic unification of the sensory neuron axons. The connectivity of the vomernasal sensorglomery neurons to mitral cells is precise, with mitral cell dendrites targeting the

. There is evidence against the presence of a functional accessory olfactory bulb in humans and other higher primates. The AOB is divided into two main subregions, anterior and posterior, which receive segregated synaptic inputs from two main categories of vomeronasal sensory neurons, V1R and V2R, respectively. This appears as a clear functional specialization, given the differential role of the two populations of sensory neurons in detecting chemical stimuli of different type and molecular weight. Although it doesn't seem to be maintained centrally, where mitral cell projections from both sides of the AOB converge. A clear difference of the AOB circuitry, compared to the rest of the bulb, is its heterogeneous connectivity between mitral cells and vomeronasal sensory afferents within neuropil glomeruli. AOB mitral cells indeed contact through apical dendritic processes glomeruli formed by afferents of different receptor neurons, thus breaking the one-receptor-one-neuron rule which generally holds for the main olfactory system. This implies that stimuli sensed through the VNO and elaborated in the AOB are subjected to a different and probably more complex level of elaboration. Accordingly, AOB mitral cells show clearly different firing patterns compared to other bulbar projection neurons. Additionally, top down input to the olfactory bulb differentially affects olfactory outputs.

Further processing

The olfactory bulb sends olfactory information to be further processed in the amygdala, the

(OFC) and the

where it plays a role in emotion, memory and learning. The main olfactory bulb connects to the amygdala via the

of the

and directly projects from the main olfactory bulb to specific amygdala areas. The amygdala passes olfactory information on to the

. The orbitofrontal cortex, amygdala, hippocampus,

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

, and olfactory bulb have many interconnections directly and indirectly through the cortices of the primary olfactory cortex. These connections are indicative of the association between the olfactory bulb and higher areas of processing, specifically those related to emotion and memory.

Amygdala

Associative learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machines; there is also evidence for some kind of l ...

between odors and behavioral responses takes place in the amygdala. The odors serve as the reinforcers or the punishers during the associative learning process; odors that occur with positive states reinforce the behavior that resulted in the positive state while odors that occur with negative states do the opposite. Odor cues are coded by neurons in the amygdala with the behavioral effect or emotion that they produce. In this way odors reflect certain emotions or physiological states. Odors become associated with pleasant and unpleasant responses, and eventually the odor becomes a cue and can cause an emotional response. These odor associations contribute to emotional states such as fear. Brain imaging shows amygdala activation correlated with pleasant and unpleasant odors, reflecting the association between odors and emotions.

Hippocampus

The

aids in olfactory memory and learning as well. Several olfaction-memory processes occur in the hippocampus. Similar to the process in the amygdala, an odor is associated with a particular reward, i.e. the smell of food with receiving sustenance. Odor in the hippocampus also contributes to the formation of episodic memory; the memories of events at a specific place or time. The time at which certain neurons fire in the hippocampus is associated by neurons with a stimulus such as an odor. Presentation of the odor at a different time may cause recall of the memory, therefore odor aids in recall of episodic memories.

Olfactory coding in Habenula

In lower vertebrates (lampreys and teleost fishes), mitral cell (principal olfactory neurons) axons project exclusively to the right hemisphere of Habenula in an asymmetric manner. It is reported that dorsal Habenula (Hb) are functional asymmetric with predominant odor responses in right hemisphere. It was also shown that Hb neurons are spontaneous active even in absence of olfactory stimulation. These spontaneous active Hb neurons are organized into functional clusters which were proposed to govern olfactory responses. (Jetti, SK. et al. 2014, Current Biology) ;Depression models Further evidence of the link between the olfactory bulb and emotion and memory is shown through animal depression models. Olfactory bulb removal in rats effectively causes structural changes in the amygdala and hippocampus and behavioral changes similar to that of a person with depression. Researchers use rats with olfactory bulbectomies to research antidepressants. Research has shown that removal of the olfactory bulb in rats leads to dendrite reorganization, disrupted cell growth in the hippocampus, and decreased

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...

in the hippocampus. These hippocampal changes due to olfactory bulb removal are associated with behavioral changes characteristic of depression, demonstrating the correlation between the olfactory bulb and emotion. The hippocampus and amygdala affect odor perception. During certain physiological states such as hunger a food odor may seem more pleasant and rewarding due to the associations in the amygdala and hippocampus of the food odor stimulus with the reward of eating.

Orbitofrontal cortex

Olfactory information is sent to the primary olfactory cortex, where projections are sent to the

. The OFC contributes to this odor-reward association as well as it assesses the value of a reward, i.e. the nutritional value of a food. The OFC receives projections from the

, amygdala, and parahippocampal cortices. Neurons in the OFC that encode food reward information activate the reward system when stimulated, associating the act of eating with reward. The OFC further projects to the anterior cingulate cortex where it plays a role in appetite. The OFC also associates odors with other stimuli, such as taste. Odor perception and discrimination also involve the OFC. The spatial odor map in the glomeruli layer of the olfactory bulb may contribute to these functions. The odor map begins processing of olfactory information by spatially organizing the glomeruli. This organizing aids the olfactory cortices in its functions of perceiving and discriminating odors.

Adult neurogenesis

The olfactory bulb is, along with both the

subventricular zone The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...

and the subgranular zone of the dentate gyrus of the hippocampus, one of only three structures in the brain observed to undergo continuing neurogenesis in adult mammals. In most mammals, new neurons are born from neural stem cells in the sub-ventricular zone and migrate rostrally towards the main and accessory olfactory bulbs. Within the olfactory bulb these immature neuroblasts develop into fully functional granule cell interneurons and periglomerular cell interneurons that reside in the granule cell layer and glomerular layers, respectively. The olfactory sensory neuron axons that form synapses in olfactory bulb glomeruli are also capable of regeneration following regrowth of an olfactory sensory neuron residing in the olfactory epithelium. Despite dynamic turnover of sensory axons and interneurons, the projection neurons (mitral and tufted neurons) that form synapses with these axons are not structurally plastic. The function of adult neurogenesis in this region remains a matter of study. The survival of immature neurons as they enter the circuit is highly sensitive to olfactory activity and in particular associative learning tasks. This has led to the hypothesis that new neurons participate in learning processes. No definitive behavioral effect has been observed in loss-of-function experiments suggesting that the function of this process, if at all related to olfactory processing, may be subtle.

Clinical significance

The olfactory lobe is a structure of the vertebrate forebrain involved in olfaction, or sense of smell. Destruction of the olfactory bulb results in ipsilateral

Other animals

Evolution

Comparing the structure of the olfactory bulb among vertebrate species, such as the leopard frog and the

lab mouse The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species '' Mus musculus''. They are the most commonly ...

, reveals that they all share the same fundamental layout (five layers containing the nuclei of three major cell types; see "Anatomy" for details), despite being dissimilar in shape and size. A similar structure is shared by the analogous olfactory center in the fruit fly '' Drosophila melanogaster'', the antennal lobe. One possibility is that vertebrate olfactory bulb and insect antennal lobe structure may be similar because they contain an optimal solution to a

computational problem In theoretical computer science, a computational problem is a problem that may be solved by an algorithm. For example, the problem of factoring :"Given a positive integer ''n'', find a nontrivial prime factor of ''n''." is a computational probl ...

experienced by all olfactory systems and thus may have evolved independently in different phyla – a phenomenon generally known as

convergent evolution Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last com ...

"The increase of brain size relative to body size— encephalization—is intimately linked with human evolution. However, two genetically different evolutionary lineages, Neanderthals and modern humans, have produced similarly large-brained human species. Thus, understanding human brain evolution should include research into specific cerebral reorganization, possibly reflected by brain shape changes. Here we exploit developmental integration between the brain and its underlying skeletal base to test hypotheses about brain evolution in ''
Homo ''Homo'' () is the genus that emerged in the (otherwise extinct) genus '' Australopithecus'' that encompasses the extant species ''Homo sapiens'' ( modern humans), plus several extinct species classified as either ancestral to or closely relat ...
''. Three-dimensional geometric morphometric analyses of endobasicranial shape reveal previously undocumented details of evolutionary changes in '' Homo sapiens''. Larger olfactory bulbs, relatively wider orbitofrontal cortex, relatively increased and forward projecting temporal lobe poles appear unique to modern humans. Such brain reorganization, beside physical consequences for overall skull shape, might have contributed to the evolution of ''H. sapiens learning and social capacities, in which higher olfactory functions and its cognitive, neurological behavioral implications could have been hitherto underestimated factors."

References

External links

* {{Authority control Olfactory system Cerebrum Limbic system