View source for Olfactory bulb

{{Short description|Neural structure}}
{{Infobox Brain
| Name        = Olfactory bulb
| Latin       = bulbus olfactorius
| Image       = 1543,Vesalius'OlfactoryBulbs.jpg
| Caption     = Human brain seen from below. [[Vesalius]]' ''Fabrica'', 1543. Olfactory bulbs and [[olfactory tracts]] outlined in red
| Image2      = Head olfactory nerve - olfactory bulb en.png
| Caption2    = Sagittal section of human head.
| IsPartOf    =
| System      = [[Olfactory system|Olfactory]]
| Components  =
| Artery      =
| Vein        =
| Acronym     =
}}
[[File:Mouse MOB three color.jpg|thumb| Coronal image of [[mouse]] main olfactory bulb cell nuclei.<BR/>'''Blue''' – Glomerular layer; <BR/>'''Red''' – External Plexiform and [[Mitral cell]] layer;<BR/>'''Green''' – Internal Plexiform and [[Granule cell]] layer.<BR/>Top of image is [[Dorsum (biology)|dorsal]] aspect, right of image is [[Human anatomical terms#Anatomical directions|lateral]] aspect.  Scale, ventral to dorsal, is approximately 2mm.]]
The '''olfactory bulb''' ([[Latin]]: ''bulbus olfactorius'') is a [[grey matter|neural structure]] of the [[vertebrate]] [[forebrain]] involved in [[olfaction]], the sense of [[odor|smell]]. It sends olfactory information to be further processed in the [[amygdala]], the [[orbitofrontal cortex]] (OFC) and the [[hippocampus]] 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]] of the [[primary olfactory cortex]] 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]] [[anosmia]], while irritative [[lesion]]s of the [[uncus]] can result in olfactory and [[gustatory]] hallucinations.

[[File:Early Olfactory System.svg|thumbnail|Flow of olfactory information from receptors to glomeruli layer]]

==Structure==
In most vertebrates, the olfactory bulb is the most [[Anatomical terms of location#Directional terms|rostral]] (forward) part of the brain, as seen in rats. In humans, however, the olfactory bulb is on the [[Anatomical terms of location#Superior and inferior|inferior]] (bottom) side of the brain. The olfactory bulb is supported and protected by the [[cribriform plate]] of the [[ethmoid bone]], which in mammals separates it from the [[olfactory epithelium]], 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 [[cytoarchitecture|cellular architecture]]. In order from surface to the center the layers are:
*[[Glomerulus (olfaction)|Glomerular]] layer
*External plexiform layer
*[[Mitral cell]] 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 nerve fiber|afferent nerves]], made up of the axons from approximately ten million [[olfactory receptor neuron]]s in the [[olfactory mucosa]], a region of the [[nasal cavity]]. The ends of the axons cluster in spherical structures known as [[glomerulus (olfaction)|glomeruli]] such that each glomerulus receives input primarily from olfactory receptor neurons that express the same [[olfactory receptor]]. The glomerular layer of the olfactory bulb is the first level of [[Synapses|synaptic processing]].<ref name="Hamilton Heinbockel 2005">{{cite journal|last1=Hamilton|first1=K.A.| last2=Heinbockel|first2=T.| last3=Ennis|first3=M.|last4=Szabó|first4=G.|last5=Erdélyi|first5=F.|last6=Hayar|first6=A.|title=Properties of external plexiform layer interneurons in mouse olfactory bulb slices|journal=Neuroscience| volume=133| issue=3|year=2005|pages=819–829|issn=0306-4522|doi=10.1016/j.neuroscience.2005.03.008|pmid=15896912| pmc=2383877}}</ref>

The glomerular 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 glomerular layer may be used for perception of odor in the olfactory cortex.<ref name="Mori 2006">{{cite journal |vauthors=Mori K, Takahashi YK, Igarashi KM, Yamaguchi M |title=Maps of odorant molecular features in the Mammalian olfactory bulb |journal=Physiol. Rev. |volume=86 |issue=2 |pages=409–33 |date=April 2006 |pmid=16601265 |doi=10.1152/physrev.00021.2005 }}</ref>

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]] and some mitral cells.  It does not contain many [[cell bodies]], rather mostly [[dendrites]] of mitral cells and GABAergic granule cells <ref name="Spors Albeanu 2012">{{cite journal|last1=Spors|first1=H.| last2=Albeanu| first2=D. F.| last3=Murthy|first3=V. N.|last4=Rinberg|first4=D.| last5=Uchida|first5=N.| last6=Wachowiak| first6=M.|last7=Friedrich|first7=R. W.|title=Illuminating Vertebrate Olfactory Processing|journal=Journal of Neuroscience|volume=32|issue=41| year=2012|pages=14102–14108a| doi=10.1523/JNEUROSCI.3328-12.2012|pmid=23055479|pmc=3752119}}</ref> are also permeated by dendrites from neurons called [[mitral cell]]s, which in turn output to the [[piriform cortex|olfactory cortex]]. Numerous interneuron types exist in the olfactory bulb including [[periglomerular cell]]s 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.<ref name="Scott 1993">{{cite journal |vauthors=Scott JW, Wellis DP, Riggott MJ, Buonviso N |title=Functional organization of the main olfactory bulb |journal=Microsc. Res. Tech. |volume=24 |issue=2 |pages=142–56 |date=February 1993 |pmid=8457726 |doi=10.1002/jemt.1070240206 |s2cid=6135866 }}</ref>

== 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 (signal processing)|filter]], 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 [[Primary olfactory cortex|olfactory cortex]],  [[amygdala]], [[neocortex]], [[hippocampus]], [[locus coeruleus]], and [[substantia nigra]].<ref>{{cite book|author1=Prof. Leon Zurawicki|title=Neuromarketing: Exploring the Brain of the Consumer|date=2 Sep 2010|publisher=Springer Science & Business Media|isbn=978-3-540-77828-8|page=22|url=https://books.google.com/books?id=gy45SfmuxK4C&q=However%2C+the+olfactory+bulb+also+receives+%22top-down%22+information+from+such+brain+areas+as+the+amygdala&pg=PA22|access-date=4 July 2015}}</ref>
Its potential functions can be placed into four non-exclusive categories:{{citation needed|date=December 2013}}

*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]], 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.<ref name="Mori 2006"/>

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.<ref name="Spors Albeanu 2012"/> Temporal patterns may have effect in later processing of spatial awareness of odorant.{{citation needed|date=December 2013}} For example, synchronized mitral cell spike trains appear to help to discriminate similar odors better than when those spike trains are not synchronized.<ref>{{cite book|last1=Linster|first1=Christiane|last2=Cleland|first2=Thomas|title=20 Years of Computational Neuroscience |chapter=Spatiotemporal Coding in the Olfactory System |date=17 June 2013|volume=9|pages=229–242|doi=10.1007/978-1-4614-1424-7_11|isbn=978-1-4614-1423-0}}</ref> A well known model<ref name=":0">{{Cite journal |last1=Li |first1=Zhaoping |last2=Hopfield |first2=J. J. |date=1989-09-01 |title=Modeling the olfactory bulb and its neural oscillatory processings |url=https://doi.org/10.1007/BF00200803 |journal=Biological Cybernetics |language=en |volume=61 |issue=5 |pages=379–392 |doi=10.1007/BF00200803 |pmid=2551392 |s2cid=7932310 |issn=1432-0770|url-access=subscription }}</ref> is that the bulbar neural circuit transforms the odor information in the receptors to a population pattern of neural oscillatory activities<ref>{{Cite journal |last=Freeman |first=Walter J |date=1978-05-01 |title=Spatial properties of an EEG event in the olfactory bulb and cortex |url=https://dx.doi.org/10.1016/0013-4694%2878%2990126-8 |journal=Electroencephalography and Clinical Neurophysiology |language=en |volume=44 |issue=5 |pages=586–605 |doi=10.1016/0013-4694(78)90126-8 |pmid=77765 |issn=0013-4694|url-access=subscription }}</ref> in the mitral cell population,<ref name=":0" /> and this pattern is then recognized by the associative memories of olfactory objects in the olfactory cortex.<ref>{{Cite journal |last1=Haberly |first1=Lewis B. |last2=Bower |first2=James M. |date=1989-01-01 |title=Olfactory cortex: model circuit for study of associative memory? |url=https://dx.doi.org/10.1016/0166-2236%2889%2990025-8 |journal=Trends in Neurosciences |language=en |volume=12 |issue=7 |pages=258–264 |doi=10.1016/0166-2236(89)90025-8 |pmid=2475938 |s2cid=3947494 |issn=0166-2236|url-access=subscription }}</ref><ref name=":1">{{Cite journal |last=Zhaoping |first=Li |date=2016-10-01 |title=Olfactory object recognition, segmentation, adaptation, target seeking, and discrimination by the network of the olfactory bulb and cortex: computational model and experimental data |url=https://www.sciencedirect.com/science/article/pii/S2352154616300766 |journal=Current Opinion in Behavioral Sciences |series=Computational modeling |language=en |volume=11 |pages=30–39 |doi=10.1016/j.cobeha.2016.03.009 |s2cid=27989941 |issn=2352-1546|url-access=subscription }}</ref> 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,<ref name=":1" /><ref>{{Cite journal |last1=Frank |first1=Marion E. |last2=Fletcher |first2=Dane B. |last3=Hettinger |first3=Thomas P. |date=2017-09-01 |title=Recognition of the Component Odors in Mixtures |journal=Chemical Senses |volume=42 |issue=7 |pages=537–546 |doi=10.1093/chemse/bjx031 |issn=1464-3553 |pmc=5863551 |pmid=28641388}}</ref> or can enhance sensitivity to a target odor during odor search.<ref>{{Cite journal |last1=Stevenson |first1=Richard J. |last2=Case |first2=Trevor I. |date=2005-04-01 |title=Olfactory imagery: A review |journal=Psychonomic Bulletin & Review |language=en |volume=12 |issue=2 |pages=244–264 |doi=10.3758/BF03196369 |pmid=16082803 |s2cid=43129982 |issn=1531-5320|doi-access=free }}</ref><ref name=":1" />

=== 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]] 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.<ref name="Hamilton Heinbockel 2005"/>  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.<ref name="Scott 1993"/>

There is little information regarding the function of the internal plexiform layer, which lies between the mitral cell layer and the granule cell layer.{{citation needed|date=December 2013}}

;Granule cell layer
The basal [[dendrites]] of [[mitral cells]] are connected to interneurons known as [[granule cells]], which may produce [[lateral inhibition]] between mitral cells.  The synapses between mitral and granule cells are of the rare "dendro-dendritic" class, with both sides of the synapse being 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 bidirectionality, 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.<ref name="Scott 1993"/>  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 aids in odor discrimination.<ref name="Hamilton Heinbockel 2005"/>  Other research suggests that the lateral inhibition contributes to differentiated odor responses, which aids in the processing and perception of distinct odors.<ref name="Scott 1993"/> There is also evidence of cholinergic effects on granule cells that enhance depolarization of granule cells, making them more excitable and increasing the inhibition of mitral cells.  This may contribute to an output from the olfactory bulb that would more closely resemble the glomerular odor map.<ref name="Pressler Inoue 2007">{{cite journal|last1=Pressler|first1=R. T.|last2=Inoue|first2=T.|last3=Strowbridge|first3=B. W.|title=Muscarinic Receptor Activation Modulates Granule Cell Excitability and Potentiates Inhibition onto Mitral Cells in the Rat Olfactory Bulb|journal=Journal of Neuroscience| volume=27| issue=41| year=2007| pages=10969–10981| doi=10.1523/JNEUROSCI.2961-07.2007 |pmid=17928438|pmc=6672850}}</ref><ref>{{cite journal|last1=Smith|first1=RS|last2=Hu|first2=R|last3=DeSouza|first3=A|last4=Eberly|first4=CL|last5=Krahe|first5=K|last6=Chan|first6=W|last7=Araneda|first7=RC|title=Differential Muscarinic Modulation in the Olfactory Bulb.|journal=The Journal of Neuroscience|date=29 July 2015|volume=35|issue=30|pages=10773–85|doi=10.1523/JNEUROSCI.0099-15.2015|pmid=26224860|pmc=4518052}}</ref>
Olfaction is distinct from the other [[sensory system]]s where peripheral [[sensory receptor]]s have a relay in the [[diencephalon]]. Therefore, the olfactory bulb plays this role for the [[olfactory system]].

=== 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#Evidence for existence in humans|vomeronasal organ]] sends projections to the accessory olfactory bulb<ref name="Taniguchi 2011">{{Cite journal  | last1 = Taniguchi | first1 = K. | last2 = Saito | first2 = S. | last3 = Taniguchi | first3 = K. | title = Phylogenic outline of the olfactory system in vertebrates. | journal = J Vet Med Sci | volume = 73 | issue = 2 | pages = 139–47 |date=Feb 2011 | pmid = 20877153 | doi=10.1292/jvms.10-0316| doi-access = free }}</ref><ref>{{cite book|last1=Carlson|first1=Neil R.|title=Physiology of behavior|date=2013|publisher=Pearson|location=Boston|isbn=978-0205239399|page=335|edition=11th}}</ref> 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 [[olfactory epithelium]] that detects chemical stimuli relevant for social and reproductive behaviors, but probably also generic odorants.<ref>{{cite journal|last=Trinh|first=K.|author2=Storm DR.|title=Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium.|journal=Nat Neurosci|year=2003|volume=6|issue=5|pages=519–25|pmid=12665798|doi=10.1038/nn1039|s2cid=8289755}}</ref> It has been hypothesized that, in order for the vomernasal pump to turn on, the main olfactory epithelium must first detect the appropriate odor.<ref name="Slotnick 2010">{{Cite journal  | last1 = Slotnick | first1 = B. | last2 = Restrepo | first2 = D. | last3 = Schellinck | first3 = H. | last4 = Archbold | first4 = G. | last5 = Price | first5 = S. | last6 = Lin | first6 = W. | title = Accessory olfactory bulb function is modulated by input from the main olfactory epithelium. | journal = Eur J Neurosci | volume = 31 | issue = 6 | pages = 1108–16 |date=Mar 2010 | doi = 10.1111/j.1460-9568.2010.07141.x | pmid = 20377623 | pmc = 3745274}}</ref> 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.<ref name="Hovis 2012">{{Cite journal  | last1 = Hovis | first1 = KR. | last2 = Ramnath | first2 = R. | last3 = Dahlen | first3 = JE. | last4 = Romanova | first4 = AL. | last5 = LaRocca | first5 = G. | last6 = Bier | first6 = ME. | last7 = Urban | first7 = NN. | title = Activity regulates functional connectivity from the vomeronasal organ to the accessory olfactory bulb. | journal = J Neurosci | volume = 32 | issue = 23 | pages = 7907–16 |date=Jun 2012 | doi = 10.1523/JNEUROSCI.2399-11.2012 | pmid = 22674266 | pmc = 3483887 }}</ref> These are transmitted to the [[amygdala]] and [[hypothalamus]] and therefore are directly involved in sex hormone activity and may influence aggressiveness and mating behavior.<ref name="Trotier 2011">{{Cite journal  | last1 = Trotier | first1 = D. | title = Vomeronasal organ and human pheromones. | journal = European Annals of Otorhinolaryngology, Head and Neck Diseases| volume = 128 | issue = 4 | pages = 184–90 |date=Sep 2011 | doi = 10.1016/j.anorl.2010.11.008 | pmid = 21377439 | doi-access = free }}</ref> 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 vomeronasal sensory neurons to mitral cells is precise, with mitral cell dendrites targeting the [[Glomerulus (olfaction)|glomeruli]].<ref name="Hovis 2012"/> There is evidence against the presence of a functional accessory olfactory bulb in humans and other higher primates.<ref name="Brennan 2006">{{cite journal |vauthors=Brennan PA, Zufall F |title=Pheromonal communication in vertebrates |journal=Nature |volume=444 |issue=7117 |pages=308–15 |date=November 2006 |pmid=17108955 |doi=10.1038/nature05404 |bibcode=2006Natur.444..308B |s2cid=4431624 }}</ref>

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 types and molecular weights. However, it does not 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 connect through apical dendritic processes of the 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 subject to a different and probably more complex level of elaboration. Accordingly, AOB mitral cells show different firing patterns compared to other bulbar projection neurons.<ref name=Shpak>{{cite journal|year=2012|doi=10.1523/JNEUROSCI.4397-11.2012|pmid=22553031|pmc=6622135|title=Calcium-Activated Sustained Firing Responses Distinguish Accessory from Main Olfactory Bulb Mitral Cells|journal=Journal of Neuroscience|volume=32|issue=18|pages=6251–62|last1=Shpak|first1=G.|last2=Zylbertal|first2=A.|last3=Yarom|first3=Y.|last4=Wagner|first4=S.}}</ref> Additionally, top down input to the olfactory bulb differentially affects olfactory outputs.<ref>{{cite journal|last1=Smith|first1=RS|last2=Hu|first2=R|last3=DeSouza|first3=A|last4=Eberly|first4=CL|last5=Krahe|first5=K|last6=Chan|first6=W|last7=Araneda|first7=RC|title=Differential Muscarinic Modulation in the Olfactory Bulb.|journal=The Journal of Neuroscience|date=29 July 2015|volume=35|issue=30|pages=10773–85|doi=10.1523/JNEUROSCI.0099-15.2015|pmid=26224860|pmc=4518052}}</ref>

=== Further processing===
The olfactory bulb sends olfactory information to be further processed in the [[amygdala]], the [[orbitofrontal cortex]] (OFC) and the [[hippocampus]] where it plays a role in emotion, memory and learning.  The main olfactory bulb connects to the amygdala via the [[piriform cortex]] of the [[primary olfactory cortex]] and directly projects from the main olfactory bulb to specific amygdala areas.<ref name="Royet 2004">{{cite journal |vauthors=Royet JP, Plailly J |title=Lateralization of olfactory processes |journal=Chem. Senses |volume=29 |issue=8 |pages=731–45 |date=October 2004 |pmid=15466819 |doi=10.1093/chemse/bjh067 |doi-access=free }}</ref> The amygdala passes olfactory information on to the [[hippocampus]].  The orbitofrontal cortex, amygdala, hippocampus, [[thalamus]], 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.<ref name="Royet 2004" />

==== Amygdala ====
[[Associative learning]] 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.<ref name="Kadohisa 2013">{{cite journal |author=Kadohisa M |title=Effects of odor on emotion, with implications |journal=Front Syst Neurosci |volume=7 |pages=66 |year=2013 |pmid=24124415 |pmc=3794443 |doi=10.3389/fnsys.2013.00066|doi-access=free }}</ref> 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.<ref name="Kadohisa 2013" />

==== Hippocampus ====
The [[hippocampus]] also aids in olfactory memory and learning.  Several olfaction-memory processes occur in the hippocampus.  Similar to the process in the amygdala, an odor is associated with a particular reward, such as the smell of food and receiving sustenance.<ref name="Rolls 2010">{{cite journal |author=Rolls ET |title=A computational theory of episodic memory formation in the hippocampus |journal=Behav. Brain Res. |volume=215 |issue=2 |pages=180–96 |date=December 2010 |pmid=20307583 |doi=10.1016/j.bbr.2010.03.027|s2cid=13605251 }}</ref>  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 with a stimulus such as an odor.  Presentation of the odor at a different time may cause recall of the memory, so that odor aids in recall of episodic memories.<ref name="Rolls 2010" />

==== Olfactory coding in the habenula ====
In lower vertebrates (lampreys and teleost fishes), mitral cell (principal olfactory neurons) axons project exclusively to the right hemisphere of the [[habenula]]. Dorsal habenulae (Hb) are functionally asymmetric with predominant odor responses in the right hemisphere. Hb neurons are spontaneously active even in the absence of olfactory stimulation. These spontaneously active Hb neurons are organized into functional clusters, which may govern olfactory responses.<ref>Jetti, SK. et al. 2014, Current Biology</ref>

;Depression models 
Further evidence of the link between the olfactory bulb and emotion and memory is shown through [[Animal models of depression|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.<ref name="Song 2005">{{Cite journal | last1 = Song | first1 = C. | last2 = Leonard | first2 = BE. | title = The olfactory bulbectomised rat as a model of depression | journal = Neuroscience & Biobehavioral Reviews | volume = 29 | issue = 4–5 | pages = 627–47 | year = 2005 | doi = 10.1016/j.neubiorev.2005.03.010 | pmid = 15925697 | s2cid = 42450349 }}</ref> Removal of the olfactory bulb in rats leads to [[dendrite]] reorganization, disrupted cell growth in the hippocampus, and decreased [[neuroplasticity]] 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.<ref name="Morales-Medina 2013">{{Cite journal | last1 = Morales-Medina | first1 = JC. | last2 = Juarez | first2 = I. | last3 = Venancio-García | first3 = E. | last4 = Cabrera | first4 = SN. | last5 = Menard | first5 = C. | last6 = Yu | first6 = W. | last7 = Flores | first7 = G. | last8 = Mechawar | first8 = N. | last9 = Quirion | first9 = R. | title = Impaired structural hippocampal plasticity is associated with emotional and memory deficits in the olfactory bulbectomized rat | journal = Neuroscience | volume = 236 | pages = 233–43 |date=Apr 2013 | doi = 10.1016/j.neuroscience.2013.01.037 | pmid = 23357118 | s2cid = 32020391 }}</ref> 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 stimulus with the reward of eating.<ref name="Kadohisa 2013" />

==== Orbitofrontal cortex ====
Olfactory information is sent to the primary olfactory cortex, where projections are sent to the [[orbitofrontal cortex]]. The OFC contributes to this odor-reward association as well as it assesses the nutritional value of food.  The OFC receives projections from the [[piriform cortex]], amygdala, and parahippocampal cortices.<ref name="Kadohisa 2013" /> 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]].<ref name="Rolls 2012">{{cite journal |last=Rolls |first=ET |title= Taste, olfactory and food texture reward processing in the brain and the control of appetite. |journal=The Proceedings of the Nutrition Society |date= November 2012 |volume=71 |issue=4 |pages= 488–501 |doi= 10.1017/S0029665112000821 |pmid= 22989943|doi-access=free }}</ref>  The OFC also associates odors with other stimuli, such as taste.<ref name="Kadohisa 2013" /> Odor perception and discrimination also involve the OFC.  The spatial odor map in the glomerular layer of the olfactory bulb may contribute to these functions.  The odor map begins processing of olfactory information by spatially organizing the glomeruli.  This organisation aids the olfactory cortices in perceiving and discriminating odors.<ref name="Mori 2006"/>

===Adult neurogenesis===
The olfactory bulb is, along with both the [[subventricular 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.{{citation needed|date=March 2017}} In most mammals, new neurons are born from neural stem cells in the sub-ventricular zone and migrate rostrally towards the main <ref name="Lazarini 2011">{{Cite journal  | last1 = Lazarini | first1 = F. | last2 = Lledo | first2 = PM. | title = Is adult neurogenesis essential for olfaction? | journal = Trends in Neurosciences | volume = 34 | issue = 1 | pages = 20–30 |date=Jan 2011 | doi = 10.1016/j.tins.2010.09.006 | pmid = 20980064 | s2cid = 40745757 | url = https://hal-pasteur.archives-ouvertes.fr/pasteur-01300437/file/Box2%20%20Fig.I.pdf }}</ref> and accessory<ref>{{cite journal|last=Oboti|first=L|author2=Savalli G |author3=Giachino C |author4=De Marchis S |author5=Panzica GC |author6=Fasolo A |author7=Peretto P |title=Integration and sensory experience-dependent survival of newly-generated neurons in the accessory olfactory bulb of female mice.|journal=Eur J Neurosci|year=2009|volume=29|issue=4|pages=679–92|doi=10.1111/j.1460-9568.2009.06614.x|pmid=19200078|s2cid=36990333}}</ref> 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.{{citation needed|date=December 2013}}

{{As of|2013}} 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.<ref name="Lepousez 2013">{{Cite journal  | last1 = Lepousez | first1 = G. | last2 = Valley | first2 = MT. | last3 = Lledo | first3 = PM. | title = The impact of adult neurogenesis on olfactory bulb circuits and computations. | journal = Annual Review of Physiology | volume = 75 | pages = 339–63 | year = 2013 | doi = 10.1146/annurev-physiol-030212-183731 | pmid = 23190074 }}</ref>  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.{{citation needed|date=December 2013}}

==Clinical significance==
Destruction of the olfactory bulb results in [[ipsilateral]] [[anosmia]] while irritative [[lesion]]s of the [[uncus]] can result in olfactory and [[gustatory]] hallucinations.{{citation needed|date=November 2020}}

==Other animals==

===Evolution===
[[File:Tyrannosaurus brain aus.jpg|thumb|right|Fossil [[endocast]] of a ''[[Tyrannosaurus]]'' cranial vault, showing extensive olfactory bulb (structure to the left). Tyrannosaur dinosaurs, as well as carnivorous animals in general, have highly developed olfactory bulbs to seek out prey.]]
Comparing the structure of the olfactory bulb among vertebrate species, such as the [[rana pipiens|leopard frog]] and the [[mus musculus|lab mouse]], 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]] experienced by all olfactory systems and thus may have evolved independently in different phyla – a phenomenon generally known as [[convergent evolution]].<ref name="Ache-2010">{{Cite journal  | last1 = Ache | first1 = BW. | title = Odorant-specific modes of signaling in mammalian olfaction | journal = Chem Senses | volume = 35 | issue = 7 | pages = 533–9 |date=Sep 2010 | doi = 10.1093/chemse/bjq045 | pmid = 20519266 | pmc=2924424}}</ref><ref name="Wang-2012">{{Cite journal  | last1 = Wang | first1 = JW. | title = Presynaptic modulation of early olfactory processing in Drosophila | journal = Dev Neurobiol | volume = 72 | issue = 1 | pages = 87–99 |date=Jan 2012 | doi = 10.1002/dneu.20936 | pmid = 21688402 | pmc=3246013}}</ref>

<blockquote>"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]]''. 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."<ref name="Bastir 2011">{{Cite journal  | last1 = Bastir | first1 = M. | last2 = Rosas | first2 = A. | last3 = Gunz | first3 = P. | last4 = Peña-Melian | first4 = A. | last5 = Manzi | first5 = G. | last6 = Harvati | first6 = K. | last7 = Kruszynski | first7 = R. | last8 = Stringer | first8 = C. | last9 = Hublin | first9 = JJ. | title = Evolution of the base of the brain in highly encephalized human species | journal = Nat Commun | volume = 2 |  pages = 588 | year = 2011 | doi = 10.1038/ncomms1593 | pmid = 22158443  | bibcode = 2011NatCo...2..588B | url = https://digital.csic.es/bitstream/10261/123641/1/Nature%20Communications%202%20588%20%282011%29.pdf | doi-access = free }}</ref></blockquote>

==See also==
*[[Olfactory ensheathing glia]]
*[[Phantosmia]]
*[[Nobiletin]]

==References==
{{Reflist}}
<!-- inserted by a newbie, doesn't footnote anything specific: 25. SK Jetti, N Vendrell-Llopis, E Yaksi. Spontaneous activity governs olfactory representations in spatially organized habenular microcircuits. Current Biology 24 (4), 434-439-->

==Further reading==
*Shepherd, G. ''The Synaptic Organization of the Brain'', Oxford University Press, 5th edition (November, 2003).  {{ISBN|0-19-515956-X}}
*{{cite journal | pmid = 12951145 | year = 2003 | last1 = Halpern | first1 = M | last2 = Martínez-Marcos | first2 = A | title = Structure and function of the vomeronasal system: An update | volume = 70 | issue = 3 | pages = 245–318 | journal = Progress in Neurobiology | doi = 10.1016/S0301-0082(03)00103-5| s2cid = 31122845 | url = https://pdfs.semanticscholar.org/22f2/53336dbce6de5378b9733023db8a4ed70aa4.pdf | archive-url = https://web.archive.org/web/20171107010214/https://pdfs.semanticscholar.org/22f2/53336dbce6de5378b9733023db8a4ed70aa4.pdf | url-status = dead | archive-date = 2017-11-07 }}
*{{cite journal | pmid = 16269360 | year = 2005 | last1 = Ache | first1 = BW | last2 = Young | first2 = JM | title = Olfaction: Diverse species, conserved principles | volume = 48 | issue = 3 | pages = 417–30 | doi = 10.1016/j.neuron.2005.10.022 | journal = Neuron | s2cid = 12078554 | doi-access = free }}

==External links==
{{Commons category|Olfactory bulb}}
* {{cite web|url=http://www.tk.de/rochelexikon/pics/s13048.000-1.html|title=Anatomy diagram: 13048.000-1|work= Roche Lexicon – illustrated navigator|publisher= Elsevier|archive-url=https://web.archive.org/web/20141107120933/http://www.tk.de/rochelexikon/pics/s13048.000-1.html|archive-date=2014-11-07}}

{{Cranial nerves}}
{{Olfactory system}}
{{Basal forebrain}}
{{Authority control}}

[[Category:Olfactory system]]
[[Category:Cerebrum]]
[[Category:Limbic system]]
[[Category:Otorhinolaryngology]]