Editing Amygdala (section)

== Function ==

===Connections===
Variability in amygdala connectivity has been related to a variety of behaviors and outcomes such as fear recognition<ref>{{Cite journal |last1=McFadyen |first1=Jessica |year=2019 |title=An afferent white matter pathway from the pulvinar to the amygdala facilitates fear recognition |journal=eLife |volume=8 |doi=10.7554/eLife.40766 |pmc=6335057 |pmid=30648533 |doi-access=free}}</ref> and social network size.<ref name="ReferenceB">{{Cite journal |last1=Hampton |first1=WH |last2=Unger |first2=A |last3=Von Der Heide |first3=RJ |last4=Olson |first4=IR |year=2016 |title=Neural connections foster social connections: a diffusion-weighted imaging study of social networks |journal=Social Cognitive and Affective Neuroscience |volume=11 |issue=5 |pages=721–727 |doi=10.1093/scan/nsv153 |pmc=4847692 |pmid=26755769 |doi-access=free}}</ref> A simple view of the information processing through the amygdala follows as: the amygdala sends projections to the [[hypothalamus]], [[Septal area|septal nuclei]] and [[Stria terminalis|BNST]] (via the [[Amygdalofugal pathway|amygdalofugal tract]]), the dorsomedial thalamus (via the amygdalothalamic tract), the nuclei of the [[trigeminal nerve]] and the [[facial nerve]], the [[ventral tegmental area]], the [[locus coeruleus]], and the [[laterodorsal tegmental nucleus]].<ref name="emotion"/>

The basolateral amygdala projects to the [[nucleus accumbens]], including the medial shell.<ref name="Lalumiere2014">{{cite journal | vauthors = Lalumiere RT | title = Optogenetic dissection of amygdala functioning | journal = Frontiers in Behavioral Neuroscience | volume = 8 | pages = 107 | date = 2014 | pmid = 24723867 | pmc = 3972463 | doi = 10.3389/fnbeh.2014.00107 | doi-access = free }}</ref><ref name="Nieh2014">{{cite journal | vauthors = Nieh EH, Kim SY, Namburi P, Tye KM | title = Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors | journal = Brain Research | volume = 1511 | pages = 73–92 | date = May 2013 | pmid = 23142759 | pmc = 4099056 | doi = 10.1016/j.brainres.2012.11.001 }}</ref><ref>{{Cite journal |last1=Kamali |first1=A. |last2=Sair |first2=H. I. |last3=Blitz |first3=A. M. |last4=Riascos |first4=R. F. |last5=Mirbagheri |first5=S. |last6=Keser |first6=Z. |last7=Hasan |first7=K. M. |date=2016 |title=Revealing the ventral amygdalofugal pathway of the human limbic system using high spatial resolution diffusion tensor tractography |journal=Brain Structure & Function |volume=221 |issue=7 |pages=3561–3569 |doi=10.1007/s00429-015-1119-3 |pmid=26454651 |s2cid=253982337}}</ref><ref>{{Cite journal |pmid=29607550 |date=2018 |last1=Kamali |first1=A. |last2=Riascos |first2=R. F. |last3=Pillai |first3=J. J. |last4=Sair |first4=H. I. |last5=Patel |first5=R. |last6=Nelson |first6=F. M. |last7=Lincoln |first7=J. A. |last8=Tandon |first8=N. |last9=Mirbagheri |first9=S. |last10=Rabiei |first10=P. |last11=Keser |first11=Z. |last12=Hasan |first12=K. M. |title=Mapping the trajectory of the amygdalothalamic tract in the human brain |journal=Journal of Neuroscience Research |volume=96 |issue=7 |pages=1176–1185 |doi=10.1002/jnr.24235 |s2cid=4565237 }}</ref><ref>{{Cite journal |pmid=37148369 |date=2023 |last1=Kamali |first1=A. |last2=Milosavljevic |first2=S. |last3=Gandhi |first3=A. |last4=Lano |first4=K. R. |last5=Shobeiri |first5=P. |last6=Sherbaf |first6=F. G. |last7=Sair |first7=H. I. |last8=Riascos |first8=R. F. |last9=Hasan |first9=K. M. |title=The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System |journal=Brain Topography |volume=36 |issue=3 |pages=371–389 |doi=10.1007/s10548-023-00955-y |pmc=10164017 }}</ref> [[Glutamate (neurotransmitter)|Glutamatergic]] neurons in the basolateral amygdala send projections to the [[nucleus accumbens]] shell and core. Activation of these projections drive [[motivational salience]]. The ability of these projections to drives [[incentive salience]] is dependent upon [[dopamine receptor D1]].<ref name="Lalumiere2014" /><ref name="Nieh2014" /> The [[endocannabinoid system]] that produces lipoid neuromodulators has its specific receptors ([[Cannabinoid receptor 1|CB1]]) found in amygdalae.<ref>{{Cite journal |last=Calabrò |first=Rocco S. |last2=Cacciola |first2=Alberto |last3=Bruschetta |first3=Daniele |last4=Milardi |first4=Demetrio |last5=Quattrini |first5=Fabrizio |last6=Sciarrone |first6=Francesca |last7=la Rosa |first7=Gianluca |last8=Bramanti |first8=Placido |last9=Anastasi |first9=Giuseppe |date=2019-09-30 |title=Neuroanatomy and function of human sexual behavior: A neglected or unknown issue? |url=https://doi.org/10.1002/brb3.1389 |journal=Brain and Behavior |volume=9 |issue=12 |doi=10.1002/brb3.1389 |issn=2162-3279|pmc=6908863 }}</ref>

[[File:Gray 718-amygdala.png|thumb|[[Coronal plane|Coronal]] section of brain through intermediate mass of [[third ventricle]]. Amygdala is shown in purple.]]
The medial nucleus is involved in the sense of smell and [[pheromone]]-processing. It receives input from the [[olfactory bulb]] and [[olfactory cortex]].<ref>{{cite book |last=Carlson |first=Neil | name-list-style = vanc |title=Physiology of behavior|url=https://archive.org/details/physiologybehavi00carl_811 |url-access=limited |date=12 January 2012|publisher=Pearson|isbn=978-0205239399|page=[https://archive.org/details/physiologybehavi00carl_811/page/n356 336]}}</ref> The lateral amygdalae, which send impulses to the rest of the basolateral complexes and to the centromedial nuclei, receive input from the sensory systems. The centromedial nuclei are the main outputs for the basolateral complexes, and are involved in emotional arousal in rats and cats.<ref name="emotion" /><ref name="Solano-Castiella" /><ref>{{cite journal | vauthors = Groshek F, Kerfoot E, McKenna V, Polackwich AS, Gallagher M, Holland PC | title = Amygdala central nucleus function is necessary for learning, but not expression, of conditioned auditory orienting | journal = Behavioral Neuroscience | volume = 119 | issue = 1 | pages = 202–12 | date = February 2005 | pmid = 15727525 | pmc = 1255918 | doi = 10.1037/0735-7044.119.1.202 }}</ref>

===Emotional learning===
{{Main |Emotion and memory}}

In complex vertebrates, including humans, the amygdalae perform primary roles in the formation and storage of memories associated with emotional events. Research indicates that, during [[fear conditioning]], sensory stimuli reach the basolateral complexes of the amygdalae, particularly the lateral nuclei, where they form associations with memories of the stimuli. The association between stimuli and the aversive events they predict may be mediated by [[long-term potentiation]],<ref name="Maren 561–7">{{cite journal | vauthors = Maren S | title = Long-term potentiation in the amygdala: a mechanism for emotional learning and memory | journal = Trends in Neurosciences | volume = 22 | issue = 12 | pages = 561–7 | date = December 1999 | pmid = 10542437 | doi = 10.1016/S0166-2236(99)01465-4 | hdl = 2027.42/56238 | s2cid = 18787168 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/56238/1/marenTINS99.pdf | hdl-access = free }}</ref><ref name="ReferenceA">{{cite journal | vauthors = Blair HT, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE | title = Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning | journal = Learning & Memory | volume = 8 | issue = 5 | pages = 229–42 | year = 2001 | pmid = 11584069 | doi = 10.1101/lm.30901 | doi-access = free }}</ref> a sustained enhancement of signaling between affected neurons.<ref name='rd'>{{cite journal | vauthors = Ressler K, Davis M | title = Genetics of childhood disorders: L. Learning and memory, part 3: fear conditioning | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 42 | issue = 5 | pages = 612–5 | date = May 2003 | pmid = 12707566 | doi = 10.1097/01.CHI.0000046835.90931.32 }}</ref> There have been studies that show that damage to the amygdala can interfere with memory that is strengthened by emotion. One study examined a patient with bilateral degeneration of the amygdala. He was told a violent story accompanied by matching pictures and was observed based on how much he could recall from the story. The patient had less recollection of the story than patients with functional amygdala, showing that the amygdala has a strong connection with emotional learning.<ref>{{cite book|last=Carlson|first=Neil R. | name-list-style = vanc |title=Physiology of Behavior|url=https://archive.org/details/physiologybehavi00carl_811|url-access=limited|date=12 January 2012|publisher=Pearson|isbn=978-0205239399|page=[https://archive.org/details/physiologybehavi00carl_811/page/n384 364]}}</ref>

Emotional memories are thought to be stored in [[synapses]] throughout the brain. Fear memories, for example, are considered to be stored in the neuronal connections from the lateral nuclei to the central nucleus of the amygdalae and the [[stria terminalis|bed nuclei of the stria terminalis]] (part of the [[extended amygdala]]). These connections are not the sole site of fear memories given that the nuclei of the amygdala receive and send information to other brain regions that are important for memory such as the hippocampus. Some [[sensory neurons]] project their [[axon terminals]] to the central nucleus.<ref>{{cite book|last=Carlson|first=Neil R. | name-list-style = vanc |title=Physiology of Behavior|url=https://archive.org/details/physiologybehavi00carl_811|url-access=limited|date=12 January 2012|publisher=Pearson|isbn=978-0205239399|page=[https://archive.org/details/physiologybehavi00carl_811/page/n473 453]}}</ref> The central nuclei are involved in the genesis of many fear responses such as defensive behavior (freezing or escape responses), autonomic nervous system responses (changes in blood pressure and heart rate/tachycardia), neuroendocrine responses (stress-hormone release), etc. Damage to the amygdalae impairs both the acquisition and expression of Pavlovian fear conditioning, a form of [[classical conditioning]] of emotional responses.<ref name='rd'/> Accumulating evidence has suggested that multiple neuromodulators acting in the amygdala regulates the formation of emotional memories.<ref>{{cite journal | vauthors = Uematsu A, Tan BZ, Ycu EA, Cuevas JS, Koivumaa J, Junyent F, Kremer EJ, Witten IB, Deisseroth K, Johansen JP | display-authors = 6 | title = Modular organization of the brainstem noradrenaline system coordinates opposing learning states | journal = Nature Neuroscience | volume = 20 | issue = 11 | pages = 1602–1611 | date = November 2017 | pmid = 28920933 | doi = 10.1038/nn.4642 | s2cid = 34732905 }}</ref><ref>{{cite journal | vauthors = Tang W, Kochubey O, Kintscher M, Schneggenburger R | title = A VTA to basal amygdala dopamine projection contributes to signal salient somatosensory events during fear learning | journal = The Journal of Neuroscience | pages = JN–RM–1796-19 | date = April 2020 | volume = 40 | issue = 20 | pmid = 32277045 | doi = 10.1523/JNEUROSCI.1796-19.2020 | pmc = 7219297 }}</ref><ref>{{cite journal | vauthors = Fadok JP, Dickerson TM, Palmiter RD | title = Dopamine is necessary for cue-dependent fear conditioning | journal = The Journal of Neuroscience | volume = 29 | issue = 36 | pages = 11089–97 | date = September 2009 | pmid = 19741115 | pmc = 2759996 | doi = 10.1523/JNEUROSCI.1616-09.2009 }}</ref>

The amygdalae are also involved in appetitive (positive) conditioning. It seems that distinct neurons respond to positive and negative stimuli, but there is no clustering of these distinct neurons into clear anatomical nuclei.<ref>{{cite journal | vauthors = Paton JJ, Belova MA, Morrison SE, Salzman CD | title = The primate amygdala represents the positive and negative value of visual stimuli during learning | journal = Nature | volume = 439 | issue = 7078 | pages = 865–70 | date = February 2006 | pmid = 16482160 | pmc = 2396495 | doi = 10.1038/nature04490 | bibcode = 2006Natur.439..865P }}</ref><ref>{{cite journal | vauthors = Redondo RL, Kim J, Arons AL, Ramirez S, Liu X, Tonegawa S | title = Bidirectional switch of the valence associated with a hippocampal contextual memory engram | journal = Nature | volume = 513 | issue = 7518 | pages = 426–30 | date = September 2014 | pmid = 25162525 | pmc = 4169316 | doi = 10.1038/nature13725 | bibcode = 2014Natur.513..426R }}</ref> However, lesions of the central nucleus in the amygdala have been shown to reduce appetitive learning in rats. Lesions of the basolateral regions do not exhibit the same effect.<ref name="Dissociable roles of the central and basolateral amygdala in appetitive emotional learning">{{cite journal | vauthors = Parkinson JA, Robbins TW, Everitt BJ | title = Dissociable roles of the central and basolateral amygdala in appetitive emotional learning | journal = The European Journal of Neuroscience | volume = 12 | issue = 1 | pages = 405–13 | date = January 2000 | pmid = 10651899 | doi = 10.1046/j.1460-9568.2000.00960.x | s2cid = 25351636 }}</ref> Research like this indicates that different nuclei within the amygdala have different functions in appetitive conditioning.<ref name="pmid16545468">{{cite journal | vauthors = Balleine BW, Killcross S | s2cid = 14958970 | title = Parallel incentive processing: an integrated view of amygdala function | journal = Trends in Neurosciences | volume = 29 | issue = 5 | pages = 272–9 | date = May 2006 | pmid = 16545468 | doi = 10.1016/j.tins.2006.03.002 }}</ref><ref>{{cite journal | vauthors = Killcross S, Robbins TW, Everitt BJ | s2cid = 205028225 | title = Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala | journal = Nature | volume = 388 | issue = 6640 | pages = 377–80 | date = July 1997 | pmid = 9237754 | doi = 10.1038/41097 | bibcode = 1997Natur.388..377K }}</ref> Nevertheless, researchers found an example of appetitive emotional learning showing an important role for the basolateral amygdala: The naïve female mice are innately attracted to non-volatile pheromones contained in male-soiled bedding, but not by the male-derived volatiles, become attractive if associated with non-volatile attractive pheromones, which act as unconditioned stimulus in a case of Pavlovian associative learning.<ref>{{cite journal | vauthors = Moncho-Bogani J, Lanuza E, Hernández A, Novejarque A, Martínez-García F | title = Attractive properties of sexual pheromones in mice: innate or learned? | journal = Physiology & Behavior | volume = 77 | issue = 1 | pages = 167–76 | date = September 2002 | pmid = 12213516 | doi = 10.1016/s0031-9384(02)00842-9 | s2cid = 10583550 }}</ref> In the vomeronasal, olfactory, and emotional systems, Fos (gene family) proteins show that non-volatile pheromones stimulate the vomeronasal system, whereas air-borne volatiles activate only the olfactory system. Thus, the acquired preference for male-derived volatiles reveals an olfactory-vomeronasal associative learning. Moreover, the reward system is differentially activated by the primary pheromones and secondarily attractive odorants. Exploring the primary attractive pheromone activates the basolateral amygdala and the shell of nucleus accumbens but neither the ventral tegmental area nor the orbitofrontal cortex. In contrast, exploring the secondarily attractive male-derived odorants involves activation of a circuit that includes the basolateral amygdala, prefrontal cortex, and ventral tegmental area. Therefore, the basolateral amygdala stands out as the key center for vomeronasal-olfactory associative learning.<ref>{{cite journal | vauthors = Moncho-Bogani J, Martinez-Garcia F, Novejarque A, Lanuza E | title = Attraction to sexual pheromones and associated odorants in female mice involves activation of the reward system and basolateral amygdala | journal = The European Journal of Neuroscience | volume = 21 | issue = 8 | pages = 2186–98 | date = April 2005 | pmid = 15869515 | doi = 10.1111/j.1460-9568.2005.04036.x | s2cid = 17056127 }}</ref>

===Memory modulation===
The amygdala is also involved in the modulation of [[memory consolidation]]. Following any learning event, the [[long-term memory]] for the event is not formed instantaneously. Rather, information regarding the event is slowly assimilated into long-term (potentially lifelong) storage over time, possibly via [[long-term potentiation]]. Recent studies suggest that the amygdala regulates memory consolidation in other brain regions. Also, [[fear conditioning]], a type of memory that is impaired following amygdala damage, is mediated in part by long-term potentiation.<ref name="Maren 561–7"/><ref name="ReferenceA"/> During the consolidation period, the memory can be modulated. In particular, it appears that emotional arousal following the learning event influences the strength of the subsequent memory for that event. Greater emotional arousal following a learning event enhances a person's retention of that event. Experiments have shown that administration of [[stress hormones]] to mice immediately after they learn something enhances their retention when they are tested two days later.<ref>"Researchers Prove A Single Memory Is Processed in Three Separate Parts of the Brain" {{cite web |url=https://www.sciencedaily.com/releases/2006/02/060202182107.htm |title=Researchers Prove a Single Memory is Processed in Three Separate Parts of the Brain |access-date=2018-02-28 |url-status=live |archive-url=https://web.archive.org/web/20170912055423/https://www.sciencedaily.com/releases/2006/02/060202182107.htm |archive-date=12 September 2017}}</ref>

The amygdala, especially the basolateral nuclei, are involved in mediating the effects of emotional arousal on the strength of the memory for the event, as shown by many laboratories including that of [[James McGaugh]]. These laboratories have trained animals on a variety of learning tasks and found that drugs injected into the amygdala after training affect the animals' subsequent retention of the task. These tasks include basic [[classical conditioning]] tasks such as inhibitory avoidance, where a rat learns to associate a mild footshock with a particular compartment of an apparatus, and more complex tasks such as spatial or cued water maze, where a rat learns to swim to a platform to escape the water. If a drug that activates the amygdalae is injected into the amygdalae, the animals had better memory for the training in the task.<ref>{{cite journal | vauthors = Ferry B, Roozendaal B, McGaugh JL | s2cid = 36848472 | title = Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: a critical involvement of the amygdala | journal = Biological Psychiatry | volume = 46 | issue = 9 | pages = 1140–52 | date = November 1999 | pmid = 10560021 | doi = 10.1016/S0006-3223(99)00157-2 }}</ref>

Amygdala activity at the time of encoding information correlates with retention for that information. However, this correlation depends on the relative "emotionalness" of the information. More emotionally arousing information increases amygdalar activity, and that activity correlates with retention. Amygdala neurons show various types of [[Neural oscillation|oscillation]] during emotional arousal, such as [[Theta rhythm|theta activity]]. These synchronized neuronal events could promote [[synaptic plasticity]] (which is involved in memory retention) by increasing interactions between neocortical storage sites and temporal lobe structures involved in [[declarative memory]].<ref>{{cite journal |vauthors=Paré D, Collins DR, Pelletier JG |date=July 2002 |title=Amygdala oscillations and the consolidation of emotional memories |journal=Trends in Cognitive Sciences |volume=6 |issue=7 |pages=306–314 |doi=10.1016/S1364-6613(02)01924-1 |pmid=12110364 |s2cid=10421580}}</ref>

In rats, [[DNA damage (naturally occurring)|DNA damage]] was found to increase in the amygdala immediately after exposure to stress.<ref name="pmid20226828">{{cite journal |vauthors=Consiglio AR, Ramos AL, Henriques JA, Picada JN |s2cid=38959073 |title=DNA brain damage after stress in rats |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=34 |issue=4 |pages=652–6 |date=May 2010 |pmid=20226828 |doi=10.1016/j.pnpbp.2010.03.004 |doi-access=free }}</ref> Stress was induced by 30 minutes of restraint or by forced swimming. By seven days after exposure to these stresses, increased DNA damage was no longer detectable in the amygdala, probably because of [[DNA repair]].<ref name="pmid20226828" />

[[Buddhist monks]] who do [[Maitrī|compassion meditation]] have been shown to modulate their amygdala, along with their [[temporoparietal junction]] and [[Insular cortex|insula]], during their practice.<ref>{{cite web | title = Cultivating compassion: Neuroscientific and behavioral approaches | first = Richard J. | last = Davidson | name-list-style = vanc | url = http://ccare.stanford.edu/node/25  |access-date=2010-07-04 |url-status=dead |archive-url=https://web.archive.org/web/20100714174906/http://ccare.stanford.edu/node/25 |archive-date=14 July 2010}}</ref> In an [[Functional magnetic resonance imaging|fMRI]] study, more intensive insula activity was found in expert meditators than in novices.<ref>{{cite journal | vauthors = Lutz A, Brefczynski-Lewis J, Johnstone T, Davidson RJ | title = Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise | journal = PLOS ONE | volume = 3 | issue = 3 | pages = e1897 | date = March 2008 | pmid = 18365029 | pmc = 2267490 | doi = 10.1371/journal.pone.0001897 | veditors = Baune B | bibcode = 2008PLoSO...3.1897L | doi-access = free }}</ref>

[[File:Rorschach blot 03.jpg|thumb|[[Rorschach test]] blot 03]]

Research using [[Rorschach test]] blot 03 finds that the number of unique responses to this random figure links to larger sized amygdalae. The researchers note, "Since previous reports have indicated that unique responses were observed at higher frequency in the artistic population than in the nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the normal population might be related to creative mental activity."<ref>{{cite journal | vauthors = Asari T, Konishi S, Jimura K, Chikazoe J, Nakamura N, Miyashita Y | s2cid = 30109156 | title = Amygdalar enlargement associated with unique perception | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 46 | issue = 1 | pages = 94–9 | date = January 2010 | pmid = 18922517 | doi = 10.1016/j.cortex.2008.08.001 }}</ref>