Editing Amygdala (section)

===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>