Structure, function and genoarchitectonics of the brain’s central amygdaloid nucleus

Abstract

The review presents the latest literature describing the Central nucleus of the Amygdala complex of the brain (CE), which is an important link in the Central autonomic nervous network. It emerges in the early stages of the evolution of the telencephalon, which determines its solid phylogenetic age and explains its heteromorphy, which is manifested by the presence of several subnucleus: medial, intermediate, lateral, and laterocapsular. The review provides information about the cytoarchitectonics, neural organization of subnucleus, and neuropeptides. Among the latter, vasopressin and oxytocin received special attention in connection with the identified new way of the innervation of the amygdala complex, which has at least two origins: (1) arising from a small population of neurons localized in the intra-amygdalar portion of the bed nucleus of the stria terminalis and (2) originating from hypothalamic neurosecretory nuclei. The afferent and efferent connections of the CE are characterized. Several studies have defined the medial subnucleus as the center of the integration of incoming information to the CE and the main channel for its exit from the CE. Moreover, the center of the brainstem that controls cardiovascular, respiratory, metabolic, and motor functions is the main point where efferent connections of the CE follow. Information is provided about the main functions, including the regulation of social behavior, eating behavior, and functional reinforcement systems. The results of genetic studies indicate that CE is a derivative of the striatal division of the lateral ganglionic eminence, and its formation is influenced by the expressions of Dlx5 and Lmo4 genes.

Keywords

amygdala / central amygdaloid nucleus / cytoarchitectonics / neuronal organization / connections / functions / genoarchitectonic

References

[1] Amunts K, Kedo O, Kindler M, et al. Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anat Embryol (Berl). 2005;210(5-6):343–352. doi: 10.1007/s00429-005-0025-5

[2] Amunts K., Kedo O., Kindler M., et al. Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps // Anat Embryol (Berl). 2005. Vol. 210, N 5-6. P. 343–352. doi: 10.1007/s00429-005-0025-5

[3] Bzdok D, Laird AR, Zilles K, et al. An investigation of the structural, connectional, and functional subspecialization in the human amygdala. Hum Brain Mapp. 2013;34(12):3247–3266. doi: 10.1002/hbm.22138

[4] Bzdok D., Laird A.R., Zilles K., et al. An investigation of the structural, connectional, and functional subspecialization in the human amygdala // Hum Brain Mapp. 2013. Vol. 34, N 12. P. 3247–3266. doi: 10.1002/hbm.22138

[5] Heimer L, Van Hoesen GW, Trimble M, Zahm DS. Anatomy of neuropsychiatry: the new anatomy of the basal forebrain and its implications for neuropsychiatric illness. Amsterdam: Boston Academic Press/Elsevier; 2008. 207 p.

[6] Heimer L., Van Hoesen G.W., Trimble M., Zahm D.S. Anatomy of neuropsychiatry: the new anatomy of the basal forebrain and its implications for neuropsychiatric illness. Amsterdam: Boston Academic Press/Elsevier, 2008. 207 p.

[7] Akmaev IG, Kalimullina LB, Sharipova LA. Central Nucleus of Brains Amygdala: cytoarchitectonic, neuron organization et connections. Morphology. 2003;123(5):515–520. (In Russ).

[8] Акмаев И.Г., Калимуллина Л.Б., Шарипова Л.А. Центральное ядро миндалевидного тела мозга: цитоархитектоника, нейронная организация и связи // Морфология. 2003. Т. 123, № 5. С. 515–520.

[9] Barbier M, Fellmann D, Risold PY. Characterization of McDonald’s intermediate part of the Central nucleus of the amygdala in the rat. J Comp Neurol. 2018;526(14):2165–2186. doi: 10.1002/cne.24470

[10] Barbier M., Fellmann D., Risold P.Y. Characterization of McDonald’s intermediate part of the Central nucleus of the amygdala in the rat // J Comp Neurol. 2018. Vol. 526, N 14. P. 2165–2186. doi: 10.1002/cne.24470

[11] Neugebauer V. Amygdala pain mechanisms. Handb Exp Pharmacol. 2015;227:261–284. doi: 10.1007/978-3-662-46450-2_13

[12] Neugebauer V. Amygdala pain mechanisms // Handb Exp Pharmacol. 2015. Vol. 227. P. 261–284. doi: 10.1007/978-3-662-46450-2_13

[13] Babaev O, Piletti Chatain C, Krueger-Burg D. Inhibition in the amygdala anxiety circuitry. Exp Mol Med. 2018;50(4):1–16. doi: 10.1038/s12276-018-0063-8

[14] Babaev O., Piletti Chatain C., Krueger-Burg D. Inhibition in the amygdala anxiety circuitry // Exp Mol Med. 2018. Vol. 50, N 4. P. 1–16. doi: 10.1038/s12276-018-0063-8

[15] Cai H, Haubensak W, Anthony TE, Anderson DJ. Central amygdala PKC-δ(+) neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci. 2014;17(9):1240–1248. doi: 10.1038/nn.3767

[16] Cai H., Haubensak W., Anthony T.E., Anderson D.J. Central amygdala PKC-δ(+) neurons mediate the influence of multiple anorexigenic signals // Nat Neurosci. 2014. Vol. 17, N 9. P. 1240–1248. doi: 10.1038/nn.3767

[17] Lubashina OA, Dorofeeva AA, Pluzhnichenko EB, Panteleev SS. Localization of neurons of the Central nucleus of the amygdala, projected on the area of the paraventricular nucleus of the hypothalamus. Morphology. 2008;134(6):73–75. (In Russ).

[18] Любашина О.А., Дорофеева А.А., Плужниченко Е.Б., Пантелееев С.С. Локализация нейронов центрального ядра миндалевидного тела, проецирующихся на область паравентрикулярного ядра гипоталамуса // Морфология. 2008. Т. 134, № 6. С. 73–75.

[19] Akhmadeev AV, Kalimullina LB. Central nucleus of Brains Amygdala: structure, neurochemistry, connections and functions. Advances in the Physiological Sciences. 2020;51(3):69–86. (In Russ). doi: 10.31857/S0301179820030030

[20] Ахмадеев А.В., Калимуллина Л.Б. Центральное ядро миндалевидного комплекса мозга: структура, нейрохимия, связи и функции // Успехи физиологических наук. 2020. Т. 51, № 3. C. 69–86. doi: 10.31857/S0301179820030030

[21] Knobloch HS, Charlet A, Hoffmann LC, et al. Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron. 2012;73(3):553–566. doi: 10.1016/j.neuron.2011.11.030

[22] Knobloch H.S., Charlet A., Hoffmann L.C., et al. Evoked axonal oxytocin release in the central amygdala attenuates fear response // Neuron. 2012. Vol. 73, N 3. P. 553–566. doi: 10.1016/j.neuron.2011.11.030

[23] Kalimullina LB, Akhmadeev AV, Nagaeva DV. Electron microscopic characteristics of the dorsomedial nucleus of the amygdaloid body of the brain. Neurosci Behav Physiol. 2000;30(5):503–508. doi: 10.1007/BF02462606

[24] Kalimullina L.B., Akhmadeev A.V., Nagaeva D.V. Electron microscopic characteristics of the dorsomedial nucleus of the amygdaloid body of the brain // Neurosci Behav Physiol. 2000. Vol. 30, N 5. P. 503–508. doi: 10.1007/BF02462606

[25] Hernández-Pérez OR, Crespo-Ramírez M, Cuza-Ferrer Y, et al. Differential activation of arginine-vasopressin receptor subtypes in the amygdaloid modulation of anxiety in the rat by arginine-vasopressin. Psychopharmacology (Berl). 2018;235(4):1015–1027. doi: 10.1007/s00213-017-4817-0

[26] Hernández-Pérez O.R., Crespo-Ramírez M., Cuza-Ferrer Y., et al. Differential activation of arginine-vasopressin receptor subtypes in the amygdaloid modulation of anxiety in the rat by arginine-vasopressin // Psychopharmacology (Berl). 2018. Vol. 235, N 4. P. 1015–1027. doi: 10.1007/s00213-017-4817-0

[27] De Mota N, Reaux-Le Goazigo A, El Messari S, et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci U S A. 2004;101(28):10464–10649. doi: 10.1073/pnas.0403518101

[28] De Mota N., Reaux-Le Goazigo A., El Messari S., et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release // Proc Natl Acad Sci U S A. 2004. Vol. 101, N 28. P. 10464–10469. doi: 10.1073/pnas.0403518101

[29] Landry M, Vila-Porcile E, Hökfelt T, Calas A. Differential routing of coexisting neuropeptides in vasopressin neurons. Eur J Neurosci. 2003;17(11):579–589. doi: 10.1046/j.1460-9568.2003.02472.x

[30] Landry M., Vila-Porcile E., Hökfelt T., Calas A. Differential routing of coexisting neuropeptides in vasopressin neurons // Eur J Neurosci. 2003. Vol. 17, N 11. P. 579–589. doi: 10.1046/j.1460-9568.2003.02472.x

[31] Fujihara H, Sasaki K, Mishiro-Sato E, et al. Molecular characterization and biological function of neuroendocrine regulatory peptide-3 in the rat. Endocrinology. 2012;153(3):1377–1386. doi: 10.1210/en.2011-1539

[32] Fujihara H., Sasaki K., Mishiro-Sato E., et al. Molecular characterization and biological function of neuroendocrine regulatory peptide-3 in the rat // Endocrinology. 2012. Vol. 153, N 3. P. 1377–1386. doi: 10.1210/en.2011-1539

[33] Yamaguchi H, Sasaki K, Satomi Y, et al. Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2. J Biol Chem. 2007;282(36):26354–26360. doi: 10.1074/jbc.M701665200

[34] Yamaguchi H., Sasaki K., Satomi Y., et al. Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2 // J Biol Chem. 2007. Vol. 282, N 36. P. 26354–26360. doi: 10.1074/jbc.M701665200

[35] Bourgeais L, Gauriau C, Bernard JF. Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: a PHA-L study in the rat. Eur J Neurosci. 2001;14(2):229–255. doi: 10.1046/j.0953-816x.2001.01640.x

[36] Bourgeais L., Gauriau C, Bernard JF. Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: a PHA-L study in the rat // Eur J Neurosci. 2001. Vol. 14, N 2. P. 229–255. doi: 10.1046/j.0953-816x.2001.01640.x

[37] Huber D, Veinante P, Stoop R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science. 2005;308(5719):245–248. doi: 10.1126/science.1105636

[38] Huber D., Veinante P., Stoop R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala // Science. 2005. Vol. 308, N 5719. P. 245–248. doi: 10.1126/science.1105636

[39] Janak PH, Tye KM. From circuits to behaviour in the amygdala. Nature. 2015;517(7534):284–292. doi: 10.1038/nature14188

[40] Janak P.H., Tye K.M. From circuits to behaviour in the amygdala // Nature. 2015. Vol. 517, N 7534. P. 284–292. doi: 10.1038/nature14188

[41] Parsons RG, Ressler KJ. Implications of memory modulation for post-traumatic stress and fear disorders. Nat Neurosci. 2013;16(2):146–153. doi: 10.1038/nn.3296

[42] Parsons R.G., Ressler K.J. Implications of memory modulation for post-traumatic stress and fear disorders // Nat Neurosci. 2013. Vol. 16, N 2. P. 146–153. doi: 10.1038/nn.3296

[43] Bowman BR, Kumar NN, Hassan SF, et al. Brain sources of inhibitory input to the rat rostral ventrolateral medulla. J Comp Neurol. 2013;521(1):213–232. doi: 10.1002/cne.23175

[44] Bowman B.R., Kumar N.N., Hassan S.F., et al. Brain sources of inhibitory input to the rat rostral ventrolateral medulla // J Comp Neurol. 2013. Vol. 521, N 1. P. 213–232. doi: 10.1002/cne.23175

[45] Retson TA, Van Bockstaele EJ. Coordinate regulation of noradrenergic and serotonergic brain regions by amygdalar neurons. J Chem Neuroanat. 2013;52:9–19. doi: 10.1016/j.jchemneu.2013.04.003

[46] Retson T.A., Van Bockstaele E.J. Coordinate regulation of noradrenergic and serotonergic brain regions by amygdalar neurons // J Chem Neuroanat. 2013. Vol. 52. P. 9–19. doi: 10.1016/j.jchemneu.2013.04.003

[47] Chen YL, Li AH, Yeh TH, et al. Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons. Mol Cell Neurosci. 2009;40(1):76–88. doi: 10.1016/j.mcn.2008.09.003

[48] Chen Y.L., Li A.H., Yeh T.H., et al. Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons // Mol Cell Neurosci. 2009. Vol. 40, N 1. P. 76–88. doi: 10.1016/j.mcn.2008.09.003

[49] Cardinal RN, Parkinson JA, Hall J, Everitt BJ. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev. 2002;26(3):321–352. doi: 10.1016/s0149-7634(02)00007-6

[50] Cardinal R.N., Parkinson J.A., Hall J., Everitt BJ. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex // Neurosci Biobehav Rev. 2002. Vol. 26, N 3. P. 321–352. doi: 10.1016/s0149-7634(02)00007-6

[51] Gilpin NW, Herman MA, Roberto M. The central amygdala as an integrative hub for anxiety and alcohol use disorders. Biol Psychiatry. 2015;77(10):859–869. doi: 10.1016/j.biopsych.2014.09.008

[52] Gilpin N.W., Herman M.A., Roberto M. The central amygdala as an integrative hub for anxiety and alcohol use disorders // Biol Psychiatry. 2015. Vol. 77, N 10. P. 859–869. doi: 10.1016/j.biopsych.2014.09.008

[53] Bienkowski MS, Rinaman L. Common and distinct neural inputs to the medial central nucleus of the amygdala and anterior ventrolateral bed nucleus of stria terminalis in rats. Brain Struct Funct. 2013;218(1):187–208. doi: 10.1007/s00429-012-0393-6

[54] Bienkowski M.S., Rinaman L. Common and distinct neural inputs to the medial central nucleus of the amygdala and anterior ventrolateral bed nucleus of stria terminalis in rats // Brain Struct Funct. 2013. Vol. 218, N 1. P. 187–208. doi: 10.1007/s00429-012-0393-6

[55] Li JN, Sheets PL. Spared nerve injury differentially alters parabrachial monosynaptic excitatory inputs to molecularly specific neurons in distinct subregions of the central amygdala. Pain. 2020;161(1):166–176. doi: 10.1097/j.pain.0000000000001691

[56] Li J.N., Sheets P.L. Spared nerve injury differentially alters parabrachial monosynaptic excitatory inputs to molecularly specific neurons in distinct subregions of the central amygdala // Pain. 2020. Vol. 161, N 1. P. 166–176. doi: 10.1097/j.pain.0000000000001691

[57] Wójciak P, Remlinger-Molenda A, Rybakowski J. Rola oksytocyny i wazopresyny w czynności ośrodkowego układu nerwowego i w zaburzeniach psychicznych. Psychiatr Pol. 2012;46(6):1043–1052.

[58] Wójciak P., Remlinger-Molenda A., Rybakowski J. Rola oksytocyny i wazopresyny w czynności ośrodkowego układu nerwowego i w zaburzeniach psychicznych // Psychiatr Pol. 2012. Vol. 46, N 6. P. 1043–1052.

[59] Parker KE, Johns HW, Floros TG, Will MJ. Central amygdala opioid transmission is necessary for increased high-fat intake following 24-h food deprivation, but not following intra-accumbens opioid administration. Behav Brain Res. 2014;260:131–138. doi: 10.1016/j.bbr.2013.11.014

[60] Parker K.E., Johns H.W., Floros T.G., Will M.J. Central amygdala opioid transmission is necessary for increased high-fat intake following 24-h food deprivation, but not following intra-accumbens opioid administration // Behav Brain Res. 2014. Vol. 260. P. 131–138. doi: 10.1016/j.bbr.2013.11.014

[61] Reyes BAS, Zhang XY, Dufourt EC, et al. Neurochemically distinct circuitry regulates locus coeruleus activity during female social stress depending on coping style. Brain Struct Funct. 2019;224(4):1429–1446. doi: 10.1007/s00429-019-01837-5

[62] Reyes B.A.S., Zhang X.Y., Dufourt E.C., et al. Neurochemically distinct circuitry regulates locus coeruleus activity during female social stress depending on coping style // Brain Struct Funct. 2019. Vol. 224, N 4. P. 1429–1446. doi: 10.1007/s00429-019-01837-5

[63] Paretkar T, Dimitrov E. Activation of enkephalinergic (Enk) interneurons in the central amygdala (CeA) buffers the behavioral effects of persistent pain. Neurobiol Dis. 2019;124:364–372. doi: 10.1016/j.nbd.2018.12.005

[64] Paretkar T., Dimitrov E. Activation of enkephalinergic (Enk) interneurons in the central amygdala (CeA) buffers the behavioral effects of persistent pain // Neurobiol Dis. 2019. Vol. 124. P. 364–372. doi: 10.1016/j.nbd.2018.12.005

[65] Kung JC, Chen TC, Shyu BC, et al. Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci. 2010;17(1):29. doi: 10.1186/1423-0127-17-29

[66] Kung J.C., Chen T.C., Shyu B.C., et al. Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder // J Biomed Sci. 2010. Vol. 17, N 1. P. 29. doi: 10.1186/1423-0127-17-29

[67] Poulin JF, Bérubé P, Laforest S, Drolet G. Enkephalin knockdown in the central amygdala nucleus reduces unconditioned fear and anxiety. Eur J Neurosci. 2013;37(8):1357–1367. doi: 10.1111/ejn.12134

[68] Poulin J.F., Bérubé P., Laforest S., Drolet G. Enkephalin knockdown in the central amygdala nucleus reduces unconditioned fear and anxiety // Eur J Neurosci. 2013. Vol. 37, N 8. P. 1357–1367. doi: 10.1111/ejn.12134

[69] Tseng A, Nguyen K, Hamid A, et al. The role of endogenous beta-endorphin and enkephalins in ethanol reward. Neuropharmacology. 2013;73:290–300. doi: 10.1016/j.neuropharm.2013.06.001

[70] Tseng A., Nguyen K., Hamid A., et al. The role of endogenous beta-endorphin and enkephalins in ethanol reward // Neuropharmacology. 2013. Vol. 73. P. 290–300. doi: 10.1016/j.neuropharm.2013.06.001

[71] Karatayev O, Barson JR, Carr AJ, et al. Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake. Alcohol. 2010;44(4):323–334. doi: 10.1016/j.alcohol.2010.05.002

[72] Karatayev O., Barson J.R., Carr A.J., et al. Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake // Alcohol. 2010. Vol. 44, N 4. P. 323–334. doi: 10.1016/j.alcohol.2010.05.002

[73] Retson TA, Hoek JB, Sterling RC, Van Bockstaele EJ. Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress. Brain Struct Funct. 2015;220(6):3211–3232. doi: 10.1007/s00429-014-0851-4

[74] Retson T.A., Hoek J.B., Sterling R.C., Van Bockstaele E.J. Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress // Brain Struct Funct. 2015. Vol. 220, N 6. P. 3211–3232. doi: 10.1007/s00429-014-0851-4

[75] García-López M, Abellán A, Legaz I, et al. Histogenetic compartments of the mouse centromedial and extended amygdala based on gene expression patterns during development. J Comp Neurol. 2008;506(1):46–74. doi: 10.1002/cne.21524

[76] García-López M., Abellán A., Legaz I., et al. Histogenetic compartments of the mouse centromedial and extended amygdala based on gene expression patterns during development // J Comp Neurol. 2008. Vol. 506, N 1. P. 46–74. doi: 10.1002/cne.21524

[77] Marin O, Anderson SA, Rubenstein JL. Origin and molecular specification of striatal interneurons. J Neurosci. 2000;20(16):6063–6076. doi: 10.1523/JNEUROSCI.20-16-06063.2000 DOI: https://doi.org/10.17816/morph.110832

[78] Marin O., Anderson S.A., Rubenstein J.L. Origin and molecular specification of striatal interneurons // J Neurosci. 2000. Vol. 20, N 16. P. 6063–6076. doi: 10.1523/JNEUROSCI.20-16-06063.2000

RIGHTS & PERMISSIONS

Eco-Vector