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Neuropeptide signalling in the central nucleus of the amygdala

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Abstract

The central amygdala has a rich repertoire of neuropeptides and neuropeptide receptors. The diverse ways in which they modulate neuronal activity and influence synaptic activity are discussed here mostly in the context of fear and anxiety-related behaviour but also with respect to nociception, hunger and satiety and chronic alcohol exposure that often come together with anxiety. It appears that neuropeptides exert rather specific effects on behaviour and physiology that can be quite different from the effects evoked by opto- or chemogenetical stimulation of the central amygdala neurons that synthesise them or express their receptors. Also, neuropeptides might work synergistically or antagonistically to fine-tune the final outcome of sensory processing in the central amygdala and bring about appropriate physiological and behavioural responses to threat. Taken together, we propose that neuropeptide signalling in the central amygdala mainly serves to establish or maintain emotional homeostasis in response to threatening and other sensory stimuli.

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References

  • Andero R, Dias BG, Ressler KJ (2014) A role for Tac2 , NkB, and Nk3 receptor in normal and Dysregulated fear memory consolidation. Neuron 83:444–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bajo M, Cruz MT, Siggins GR et al (2008) Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proc Natl Acad Sci 105:8410–8415

    Article  PubMed  PubMed Central  Google Scholar 

  • Bernard JF, Bandler R (1998) Parallel circuits for emotional coping behaviour: new pieces in the puzzle. J Comp Neurol 401:429–436

    Article  CAS  PubMed  Google Scholar 

  • Betley JN, Cao ZFH, Ritola KD, Sternson SM (2013) Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell 155:1337–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beyer CE, Dwyer JM, Platt BJ et al (2010) Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation. Psychopharmacology 209:303–311

    Article  CAS  PubMed  Google Scholar 

  • Bosch OJ (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25:6807–6815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown MR, Gray TS (1988) Peptide injections into the amygdala of conscious rats: effects on blood pressure, heart rate and plasma catecholamines. Regul Pept 21:95–106

    Article  CAS  PubMed  Google Scholar 

  • Cai H, Haubensak W, Anthony TE, Anderson DJ (2014) Central amygdala PKC-δ+ neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci 17:1240–1248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campos CA, Bowen AJ, Roman CW, Palmiter RD (2018) Encoding of danger by parabrachial CGRP neurons. Nature 555:617–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciocchi S, Herry C, Grenier F et al (2010) Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468:277–282

    Article  CAS  PubMed  Google Scholar 

  • Cruz MT, Herman MA, Kallupi M, Roberto M (2012) Nociceptin/orphanin FQ blockade of corticotropin-releasing factor-induced gamma-aminobutyric acid release in central amygdala is enhanced after chronic ethanol exposure. Biol Psychiatry 71:666–676

    Article  CAS  PubMed  Google Scholar 

  • Davidson S, Lear M, Shanley L et al (2011) Differential activity by polymorphic variants of a remote enhancer that supports galanin expression in the hypothalamus and amygdala: implications for obesity, depression and alcoholism. Neuropsychopharmacology 36:2211–2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Do-Monte FH, Quiñones-Laracuente K, Quirk GJ (2015) A temporal shift in the circuits mediating retrieval of fear memory. Nature 519:460–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322:900–904

    Article  CAS  PubMed  Google Scholar 

  • Douglass AM, Kucukdereli H, Ponserre M et al (2017) Central amygdala circuits modulate food consumption through a positive-valence mechanism. Nat Neurosci 20:1384–1394

    Article  CAS  PubMed  Google Scholar 

  • Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82:966–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fadok JP, Krabbe S, Markovic M et al (2017) A competitive inhibitory circuit for selection of active and passive fear responses. Nature 542:96–100

    Article  CAS  PubMed  Google Scholar 

  • Gilpin NW, Misra K, Herman MA et al (2011) Neuropeptide Y opposes alcohol effects on gamma-aminobutyric acid release in amygdala and blocks the transition to alcohol dependence. Biol Psychiatry 69:1091–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilpin NW, Roberto M (2012) Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence. Neurosci Biobehav Rev 36:873–888

    Article  CAS  PubMed  Google Scholar 

  • Guzmán-Ramos K, Bermúdez-Rattoni F (2012) Interplay of amygdala and insular cortex during and after associative taste aversion memory formation. Rev Neurosci 23:463–471

    Article  PubMed  Google Scholar 

  • Han JS, Adwanikar H, Li Z et al (2010) Facilitation of synaptic transmission and pain responses by CGRP in the amygdala of normal rats. Mol Pain 6:1744-8069-6–10

    Article  CAS  Google Scholar 

  • Han S, Soleiman MT, Soden ME et al (2015) Elucidating an affective pain circuit that creates a threat memory. Cell 162:363–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haubensak W, Kunwar PS, Cai H et al (2010) Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468:270–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herman JP, Ostrander MM, Mueller NK, Figueiredo H (2005) Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuro-Psychopharmacol Biol Psychiatry 29:1201–1213

    Article  CAS  Google Scholar 

  • Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7:867–879

    Article  PubMed  Google Scholar 

  • Huber D, Veinante P, Stoop R (2005) Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308:245–248

    Article  CAS  PubMed  Google Scholar 

  • Iemolo A, Ferragud A, Cottone P, Sabino V (2015) Pituitary adenylate cyclase-activating peptide in the central amygdala causes anorexia and body weight loss via the melanocortin and the TrkB systems. Neuropsychopharmacology 40:1846–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iemolo A, Seiglie M, Blasio A et al (2016) Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors. Psychopharmacology 233:3269–3277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin W-Y, Liu Z, Liu D, Yu L-C (2010) Antinociceptive effects of galanin in the central nucleus of amygdala of rats, an involvement of opioid receptors. Brain Res 1320:16–21

    Article  CAS  PubMed  Google Scholar 

  • Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011) Molecular mechanisms of fear learning and memory. Cell 147:509–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keifer OP, Hurt RC, Ressler KJ, Marvar PJ (2015) The physiology of fear: reconceptualizing the role of the central amygdala in fear learning. Physiology 30:389–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knobloch HS, Charlet A, Hoffmann LC et al (2012) Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73:553–566

    Article  CAS  PubMed  Google Scholar 

  • Ku Y-H, Tan L, Li L-S, Ding X (1998) Role of corticotropin-releasing factor and substance P in pressor responses of nuclei controlling emotion and stress. Peptides 19:677–682

    Article  CAS  PubMed  Google Scholar 

  • Kuo D-Y, Yang S-F, Chu S-C et al (2010) The effect of protein kinase C-delta knockdown on anti-free radical enzyme and neuropeptide Y gene expression in phenylpropanolamine-treated rats. J Neurochem 114:1217–1230

    CAS  PubMed  Google Scholar 

  • Li H, Penzo MA, Taniguchi H et al (2013) Experience-dependent modification of a central amygdala fear circuit. Nat Neurosci 16:332–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li S-Y, Huo M-L, Wu X-Y et al (2017) Involvement of galanin and galanin receptor 1 in nociceptive modulation in the central nucleus of amygdala in normal and neuropathic rats. Sci Rep 7:15317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y-C, Chen Y-Z, Wei Y-Y et al (2015) Neurochemical properties of the synapses between the parabrachial nucleus-derived CGRP-positive axonal terminals and the GABAergic neurons in the lateral capsular division of central nucleus of amygdala. Mol Neurobiol 51:105–118

    Article  CAS  PubMed  Google Scholar 

  • Manning M, Stoev S, Chini B et al (2008) Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. In: Neumann ID, Landgraf R (eds) Progress in brain research. Elsevier, pp 473–512

  • McCormick K, Baillie GS (2014) Compartmentalisation of second messenger signalling pathways. Curr Opin Genet Dev 27:20–25

    Article  CAS  PubMed  Google Scholar 

  • Missig G, Mei L, Vizzard MA et al (2017) Parabrachial pituitary adenylate cyclase-activating polypeptide activation of amygdala endosomal extracellular signal–regulated kinase signaling regulates the emotional component of pain. Biol Psychiatry 81:671–682

    Article  CAS  PubMed  Google Scholar 

  • Missig G, Roman CW, Vizzard MA et al (2014) Parabrachial nucleus (PBn) pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the amygdala: implication for the sensory and behavioral effects of pain. Neuropharmacology 86:38–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Namburi P, Beyeler A, Yorozu S et al (2015) A circuit mechanism for differentiating positive and negative associations. Nature 520:675–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narváez M, Millón C, Borroto-Escuela D et al (2015) Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions. Brain Struct Funct 220:2289–2301

    Article  CAS  PubMed  Google Scholar 

  • Neugebauer V, Galhardo V, Maione S, Mackey SC (2009) Forebrain pain mechanisms. Brain Res Rev 60:226–242

    Article  PubMed  Google Scholar 

  • Nie Z (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303:1512–1514

    Article  CAS  PubMed  Google Scholar 

  • Penzo MA, Robert V, Li B (2014) Fear conditioning potentiates synaptic transmission onto long-range projection neurons in the lateral subdivision of central amygdala. J Neurosci 34:2432–2437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penzo MA, Robert V, Tucciarone J et al (2015) The paraventricular thalamus controls a central amygdala fear circuit. Nature 519:455–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pleil KE, Rinker JA, Lowery-Gionta EG et al (2015) NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat Neurosci 18:545–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rickenbacher E, Perry RE, Sullivan RM, Moita MA (2017) Freezing suppression by oxytocin in central amygdala allows alternate defensive behaviours and mother-pup interactions. eLife 6:e24080

    Article  PubMed  PubMed Central  Google Scholar 

  • Roberto M, Cruz MT, Gilpin NW et al (2010) Corticotropin releasing factor–induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol Psychiatry 67:831–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues SM, Schafe GE, LeDoux JE (2004) Molecular mechanisms underlying emotional learning and memory in the lateral amygdala. Neuron 44:75–91

    Article  CAS  PubMed  Google Scholar 

  • Roesler R, Kent P, Luft T et al (2014) Gastrin-releasing peptide receptor signaling in the integration of stress and memory. Neurobiol Learn Mem 112:44–52

    Article  CAS  PubMed  Google Scholar 

  • Roesler R, Kent P, Schröder N et al (2012) Bombesin receptor regulation of emotional memory. Rev Neurosci 23:571–586

    Article  CAS  PubMed  Google Scholar 

  • Sajdyk TJ, Shekhar A, Gehlert DR (2004) Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides 38:225–234

    Article  CAS  PubMed  Google Scholar 

  • Sanford CA, Soden ME, Baird MA et al (2017) A central amygdala CRF circuit facilitates learning about weak threats. Neuron 93:164–178

    Article  CAS  PubMed  Google Scholar 

  • Schiff HC, Bouhuis AL, Yu K et al (2018) An insula–central amygdala circuit for guiding tastant-reinforced choice behavior. J Neurosci 38:1418–1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi C-J, Cassell MD (1998) Cortical, thalamic, and amygdaloid connections of the anterior and posterior insular cortices. J Comp Neurol 399:440–468

    Article  CAS  PubMed  Google Scholar 

  • Stoop R, Hegoburu C, van den BE (2015) New opportunities in vasopressin and oxytocin research: a perspective from the amygdala. Annu Rev Neurosci 38:369–388

    Article  CAS  PubMed  Google Scholar 

  • Todd AJ (2010) Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 11:823–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van den Burg EH, Stindl J, Grund T et al (2015) Oxytocin stimulates extracellular Ca2+ influx through TRPV2 channels in hypothalamic neurons to exert its anxiolytic effects. Neuropsychopharmacology 40:2938–2947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veinante P, Freund-Mercier M-J (1997) Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol 383:305–325

    Article  CAS  PubMed  Google Scholar 

  • Viviani D, Charlet A, van den Burg E et al (2011) Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science 333:104–107

    Article  CAS  PubMed  Google Scholar 

  • Watanabe MA, Kucenas S, Bowman TA et al (2010) Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats. Brain Res 1309:53–65

    Article  CAS  PubMed  Google Scholar 

  • Wilensky AE, Schafe GE, Kristensen MP, LeDoux JE (2006) Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning. J Neurosci 26:12387–12396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Zhang J-T, Liu J et al (2015) Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats. J Neurochem 135:787–798

    Article  CAS  PubMed  Google Scholar 

  • Yeung M, Treit D (2012) The anxiolytic effects of somatostatin following intra-septal and intra-amygdalar microinfusions are reversed by the selective sst2 antagonist PRL2903. Pharmacol Biochem Behav 101:88–92

    Article  CAS  PubMed  Google Scholar 

  • Yu K, Ahrens S, Zhang X et al (2017) The central amygdala controls learning in the lateral amygdala. Nat Neurosci 20:1680–1685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Qi J, Li X et al (2015) Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons. Nat Neurosci 18:386–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

EvdB is supported by a Swiss Federal grant from the Commission of Technology and Innovation.

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Correspondence to Erwin H van den Burg.

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van den Burg, E.H., Stoop, R. Neuropeptide signalling in the central nucleus of the amygdala. Cell Tissue Res 375, 93–101 (2019). https://doi.org/10.1007/s00441-018-2862-6

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