Abstract
In pharmacological studies conducted on animals over the last four decades, histamine was determined to be a strong modulator of learning and memory. Activation of histamine signaling enhances memory consolidation and retrieval. Even long after learning and forgetting, it can still restore the retrieval of forgotten memories. These findings based on animal studies led to human clinical trials with histamine H3 receptor antagonists/inverse agonists, which revealed their positive effects on learning and memory. Therefore, histamine signaling is a promising therapeutic target for improving cognitive impairments in patients with various neuropsychiatric disorders, including Alzheimer’s disease. While the memory-modulatory effects of histamine receptor agonists and antagonists have been confirmed by several research groups, the underlying mechanisms remain to be elucidated. This review summarizes how the activation and inhibition of histamine signaling influence memory processes, introduces the cellular and circuit mechanisms, and discusses the relationship between the human histaminergic system and learning and memory.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Acevedo SF, Pfankuch T, Ohtsu H, Raber J (2006) Anxiety and cognition in female histidine decarboxylase knockout (Hdc-/-) mice. Behav Brain Res 168(1):92–99. https://doi.org/10.1016/j.bbr.2005.10.016
Alberini CM (2005) Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci 28(1):51–56. https://doi.org/10.1016/j.tins.2004.11.001
Alraksinen MS, Paetau A, Paljärvi L, Reinikainen K, Rlekkinen P, Suomalainen R, Panula P (1991) Histamine neurons in human hypothalamus: anatomy in normal and alzheimer diseased brains. Neuroscience 44(2):465–481. https://doi.org/10.1016/0306-4522(91)90070-5
Ambrée O, Buschert J, Zhang W, Arolt V, Dere E, Zlomuzica A (2014) Impaired spatial learning and reduced adult hippocampal neurogenesis in histamine H1-receptor knockout mice. Eur Neuropsychopharmacol 24(8):1394–1404. https://doi.org/10.1016/j.euroneuro.2014.04.006
Andersson R, Galter D, Papadia D, Fisahn A (2017) Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor. Neuropharmacology 118:13–25. https://doi.org/10.1016/j.neuropharm.2017.03.003
Arrang JM, Garbarg M, Schwartz JC (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302(5911):832–837
Atzori M, Lau D, Tansey EP, Chow A, Ozaita A, Rudy B, McBain CJ (2000) H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking. Nat Neurosci 3(8):791–798. https://doi.org/10.1038/77693
Beatty WW, Salmon DP, Butters N, Heindel WC, Granholm EL (1988) Retrograde amnesia in patients with Alzheimer’s disease or Huntington’s disease. Neurobiol Aging 9(C):181–186. https://doi.org/10.1016/S0197-4580(88)80048-4
Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (2008) BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci 105(7):2711–2716
Bekkers JM (1993) Enhancement by histamine of NMDA-mediated synaptic transmission in the hippocampus. Science 261(5117):104–106. https://doi.org/10.1126/science.8391168
Benetti F, Izquierdo I (2013) Histamine infused into basolateral amygdala enhances memory consolidation of inhibitory avoidance. Int J Neuropsychopharmacol 16(7):1539–1545. https://doi.org/10.1017/S1461145712001514
Benetti F, Guerino Furini CR, De Carvalho MJ, Provensi G, Passani MB, Baldi E, Bucherelli C, Munari L, Izquierdo I, Blandina P (2015) Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus. Proc Natl Acad Sci U S A 112(19):E2536–E2542. https://doi.org/10.1073/pnas.1506109112
Best J, Nijhout HF, Samaranayake S, Hashemi P, Reed M (2017) A mathematical model for histamine synthesis, release, and control in varicosities. Theor Biol Med Model 14(1):1–19. https://doi.org/10.1186/s12976-017-0070-9
Blandina P, Giorgetti M, Bartolini L, Cecchi M, Timmerman H, Leurs R, Pepeu G, Giovannini MG (1996a) Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats. Br J Pharmacol 119(8):1656–1664. https://doi.org/10.1111/j.1476-5381.1996.tb16086.x
Blandina P, Giorgetti M, Cecchi M, Leurs R, Timmerman H, Giovannini MG (1996b) Histamine H3 receptor inhibition of K(+)-evoked release of acetylcholine from rat cortex in vivo. Inflamm Res 45(Suppl 1):S54–S55
Blandina P, Efoudebe M, Cenni G, Mannaioni P, Passani MB (2004) Acetylcholine, histamine, and cognition: two sides of the same coin. Learn Mem 11:1–8
Blandina P, Munari L, Provensi G, Passani MB (2012) Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations? Front Syst Neurosci 6:33
Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39
Bonini JS, Da Silva WC, Da Silveira CKB, Köhler CA, Izquierdo I, Cammarota M (2011) Histamine facilitates consolidation of fear extinction. Int J Neuropsychopharmacol 14(9):1209–1217. https://doi.org/10.1017/S1461145710001501
Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79(1):59–68
Brabant C, Charlier Y, Tirelli E (2013) The histamine H3-receptor inverse agonist Pitolisant improves fear memory in mice. Behav Brain Res 243(1):199–204. https://doi.org/10.1016/j.bbr.2012.12.063
Brown RE, Fedorov NB, Haas HI, Reyman KG (1995) Histaminergic modulation of synaptic plasticity in area CA1 of rat hippocampal slices. Neuropharmacology 34(2):181–190. https://doi.org/10.1016/0028-3908(94)00138-I
Burban A, Faucard R, Armand V, Bayard C, Vorobjev V, Arrang JM (2010) Histamine potentiates N-methyl-D-aspartate receptors by interacting with an allosteric site distinct from the polyamine binding site. J Pharmacol Exp Ther 332(3):912–921. https://doi.org/10.1124/jpet.109.158543
Cacabelos R, Yamatodani A, Niigawa H, Hariguchi S, Tada K, Nishimura T, Wada H, Brandeis L, Pearson J (1989) Brain histamine in Alzheimer’s disease. Methods Find Exp Clin Pharmacol 11(5):353–360
Cangioli I, Baldi E, Mannaioni PF, Bucherelli C, Blandina P, Passani MB (2002) Activation of histaminergic H3 receptors in the rat basolateral amygdala improves expression of fear memory and enhances acetylcholine release. Eur J Neurosci 16(3):521–528
Charlier Y, Tirelli E (2011) Differential effects of histamine H 3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice. Neuroscience 193:132–142. https://doi.org/10.1016/j.neuroscience.2011.07.034
Chen Q, Luo F, Yue F, Xia J, Xiao Q, Liao X, Jiang J, Zhang J, Hu B, Gao D, He C, Hu Z (2018) Histamine enhances theta-coupled spiking and gamma oscillations in the medial entorhinal cortex consistent with successful spatial recognition. Cereb Cortex 28:2439–2457. https://doi.org/10.1093/cercor/bhx145
Chu M, Huang ZL, Qu WM, Eguchi N, Yao MH, Urade Y (2004) Extracellular histamine level in the frontal cortex is positively correlated with the amount of wakefulness in rats. Neurosci Res 49(4):417–420. https://doi.org/10.1016/j.neures.2004.05.001
Contreras M, Riveros ME, Quispe M, Sanchez C, Perdomo G, Torrealba F, Valdes JL (2016) The histaminergic tuberomamillary nucleus is involved in appetite for sex, water and amphetamine. PLoS One 11(2). https://doi.org/10.1371/journal.pone.0148484
da Silva WC, Bonini JS, Bevilaqua LRM, Izquierdo I, Cammarota M (2006) Histamine enhances inhibitory avoidance memory consolidation through a H2 receptor-dependent mechanism. Neurobiol Learn Mem 86(1):100–106. https://doi.org/10.1016/j.nlm.2006.01.001
da Silveira CKB, Furini CRG, Benetti F, Monteiro SDC, Izquierdo I (2013) The role of histamine receptors in the consolidation of object recognition memory. Neurobiol Learn Mem 103:64–71. https://doi.org/10.1016/j.nlm.2013.04.001
Dai H, Kaneko K, Kato H, Fujii S, Jing Y, Xu A, Sakurai E, Kato M, Okamura N, Kuramasu A, Yanai K (2007) Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors. Neurosci Res 57(2):306–313. https://doi.org/10.1016/j.neures.2006.10.020
de Almeida MA, Izquierdo I (1986) Memory facilitation by histamine. Arch Int Pharmacodyn Ther 283(2):193–198
Dere E, De Souza-Silva MA, Topic B, Spieler RE, Haas HL, Huston JP (2003) Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover. Learn Mem 10(6):510–519. https://doi.org/10.1101/lm.67603
Ellenbroek BA, Ghiabi B (2014) The other side of the histamine H3 receptor. Trends Neurosci 37(4):191–199. https://doi.org/10.1016/j.tins.2014.02.007
Ericson H, Watanabe T, Köhler C (1987) Morphological analysis of the tuberomammmillary nucleus in the rat brain: delineation of subgroups with antibody again L-histidine decarboxylase as a marker. J Comp Neurol 263(1):1–24. https://doi.org/10.1002/cne.902630102
Esbenshade TA, Browman KE, Bitner RS, Strakhova M, Cowart MD, Brioni JD (2008) The histamine H 3 receptor: an attractive target for the treatment of cognitive disorders. Br J Pharmacol 154(6):1166–1181. https://doi.org/10.1038/bjp.2008.147
Etter G, van der Veldt S, Manseau F, Zarrinkoub I, Trillaud-Doppia E, Williams S (2019) Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model. Nat Commun 10(1). https://doi.org/10.1038/s41467-019-13260-9
Fabbri R, Furini CRG, Passani MB, Provensi G, Baldi E, Bucherelli C, Izquierdo I, De Myskiw JC, Blandina P (2016) Memory retrieval of inhibitory avoidance requires histamine H\1\ receptor activation in the hippocampus. Proc Natl Acad Sci U S A 113(19):E2714–E2720. https://doi.org/10.1073/pnas.1604841113
Fauve S, Heslot F (1983) Stochastic resonance in a bistable system. Phys Lett A 97(1–2):5–7. https://doi.org/10.1016/0375-9601(83)90086-5
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L-H (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447(7141):178–182. https://doi.org/10.1038/nature05772
Frankland PW, Bontempi B (2005) The organization of recent and remote memories. Nat Rev Neurosci 6(2):119–130. https://doi.org/10.1038/nrn1607
Fujita A, Bonnavion P, Wilson MH, Mickelsen LE, Bloit J, de Lecea L, Jackson AC (2017) Hypothalamic tuberomammillary nucleus neurons: electrophysiological diversity and essential role in arousal stability. J Neurosci 37(39):0580–0517. https://doi.org/10.1523/JNEUROSCI.0580-17.2017
Giannoni P, Passani MB, Nosi D, Chazot PL, Shenton FC, Medhurst AD, Munari L, Blandina P (2009) Heterogeneity of histaminergic neurons in the tuberomammillary nucleus of the rat. Eur J Neurosci 29(12):2363–2374. https://doi.org/10.1111/j.1460-9568.2009.06765.x
Goutagny R, Gu N, Cavanagh C, Jackson J, Chabot JG, Quirion R, Krantic S, Williams S (2013) Alterations in hippocampal network oscillations and theta-gamma coupling arise before Aβ overproduction in a mouse model of Alzheimer’s disease. Eur J Neurosci 37(12):1896–1902. https://doi.org/10.1111/ejn.12233
Grove RA, Harrington CM, Mahler A, Beresford I, Maruff P, Lowy MT, Nicholls AP, Boardley RL, Berges AC, Nathan PJ, Horrigan JP (2014) A randomized, double-blind, placebo-controlled, 16-week study of the H3 receptor antagonist, GSK239512 as a monotherapy in subjects with mild-to-moderate Alzheimer’s disease. Curr Alzheimer Res 11(1):47–58
Haas H, Panula P (2003) The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci 4(2):121–130. https://doi.org/10.1038/nrn1034
Haas HL, Reiner PB (1988) Membrane properties of histaminergic tuberomammillary neurones of the rat hypothalamus in vitro. J Physiol 399(1):633–646. https://doi.org/10.1113/jphysiol.1988.sp017100
Haas HL, Sergeeva OA, Selbach O (2008) Histamine in the nervous system. Physiol Rev 88(3):1183–1241. https://doi.org/10.1152/physrev.00043.2007
Hashikawa K, Matsuki N, Nomura H (2011) Preferential arc transcription at rest in the active ensemble during associative learning. Neurobiol Learn Mem 95(4):498–504. https://doi.org/10.1016/j.nlm.2011.02.013
Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, Hu H, Mittal K, McNaughton AJM, Sritharan K, Hudson M, Stehr H, Talebi S, Moradi M, Darvish H, Rafiq MA, Mozhdehipanah H, Rashidinejad A, Samiei S, Ghadami M, Windpassinger C, Gillessen-Kaesbach G, Tzschach A, Ahmed I, Mikhailov A, James Stavropoulos D, Carter MT, Keshavarz S, Ayub M, Najmabadi H, Liu X, Ropers HH, Macheroux P, Vincent JB (2015) Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability. Hum Mol Genet 24(20):5697–5710. https://doi.org/10.1093/hmg/ddv286
Herrmann CS, Demiralp T (2005) Human EEG gamma oscillations in neuropsychiatric disorders. Clin Neurophysiol 116:2719–2733
Higuchi M, Yanai K, Okamura N, Meguro K, Arai H, Itoh M, Iwata R, Ido T, Watanabe T, Sasaki H (2000) Histamine H1 receptors in patients with Alzheimer’s disease assessed by positron emission tomography. Neuroscience 99(4):721–729. https://doi.org/10.1016/S0306-4522(00)00230-X
Hitora-Imamura N, Miura Y, Teshirogi C, Ikegaya Y, Matsuki N, Nomura H (2015) Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits. eLife 4. https://doi.org/10.7554/eLife.08274
Introini-Collison IB, Dalmaz C, McGaugh JL (1996) Amygdala β-noradrenergic influences on memory storage involve cholinergic activation. Neurobiol Learn Mem 65(1):57–64. https://doi.org/10.1006/nlme.1996.0006
Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011) Molecular mechanisms of fear learning and memory. Cell 147(3):509–524. https://doi.org/10.1016/j.cell.2011.10.009
Josselyn SA, Köhler S, Frankland PW (2015) Finding the engram. Nat Rev Neurosci 16(9):521–534. https://doi.org/10.1038/nrn4000
Kamei C, Tasaka K (1993) Effect of histamine on memory retrieval in old rats. Biol Pharm Bull 16(2):128–132. https://doi.org/10.1248/bpb.16.128
Kárpáti A, Yoshikawa T, Naganuma F, Matsuzawa T, Kitano H, Yamada Y, Yokoyama M, Futatsugi A, Mikoshiba K, Yanai K (2019) Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour. Sci Rep 9(1). https://doi.org/10.1038/s41598-019-52623-6
Katoh Y, Niimi M, Yamamoto Y, Kawamura T, Morimoto-Ishizuka T, Sawada M, Takemori H, Yamatodani A (2001) Histamine production by cultured microglial cells of the mouse. Neurosci Lett 305(3):181–184. https://doi.org/10.1016/S0304-3940(01)01835-3
Kida S, Josselyn SA, Peña de Ortiz S, Kogan JH, Chevere I, Masushige S, Silva AJ (2002) CREB required for the stability of new and reactivated fear memories. Nat Neurosci 5(4):348–355. https://doi.org/10.1038/nn819
Kindt M, Soeter M, Vervliet B (2009) Beyond extinction: erasing human fear responses and preventing the return of fear. Nat Neurosci 12(3):256–258. https://doi.org/10.1038/nn.2271
Kitamura T, Inokuchi K (2014) Role of adult neurogenesis in hippocampal-cortical memory consolidation. Mol Brain 7:1–8
Klinzing JG, Niethard N, Born J (2019) Mechanisms of systems memory consolidation during sleep. Nat Neurosci 22(10):1598–1610. https://doi.org/10.1038/s41593-019-0467-3
Köhler CA, da Silva WC, Benetti F, Bonini JS (2011) Histaminergic mechanisms for modulation of memory systems. Neural Plast 2011:328602. https://doi.org/10.1155/2011/328602
Kopelman MD, Bright P (2012) On remembering and forgetting our autobiographical pasts: retrograde amnesia and Andrew Mayes’s contribution to neuropsychological method. Neuropsychologia 50(13):2961–2972. https://doi.org/10.1016/j.neuropsychologia.2012.07.028
Kuo MC, Dringenberg HC (2008) Histamine facilitates in vivo thalamocortical long-term potentiation in the mature visual cortex of anesthetized rats. Eur J Neurosci 27(7):1731–1738. https://doi.org/10.1111/j.1460-9568.2008.06164.x
Lenz KM, Pickett LA, Wright CL, Davis KT, Joshi A, McCarthy MM (2018) Mast cells in the developing brain determine adult sexual behavior. J Neurosci 38(37):8044–8059. https://doi.org/10.1523/JNEUROSCI.1176-18.2018
Liao R, Chen Y, Cheng L, Fan L, Chen H, Wan Y, You Y, Zheng Y, Jiang L, Chen Z, Zhang X, Hu W (2019) Histamine H1 receptors in neural stem cells are required for the promotion of neurogenesis conferred by H3 receptor antagonism following traumatic brain injury. Stem Cell Rep 12(3):532–544. https://doi.org/10.1016/j.stemcr.2019.01.004
Liu L, Zhang S, Zhu YY, Fu Q, Zhu YY, Gong Y, Ohtsu H, Luo J, Wei E, Chen Z (2007) Improved learning and memory of contextual fear conditioning and hippocampal CA1 long-term potentiation in histidine decarboxylase knock-out mice. Hippocampus 8:634–641
Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S (2012) Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484(7394):381–385. https://doi.org/10.1038/nature11028
Mably AJ, Gereke BJ, Jones DT, Colgin LL (2017) Impairments in spatial representations and rhythmic coordination of place cells in the 3xTg mouse model of Alzheimer’s disease. Hippocampus 27(4):378–392. https://doi.org/10.1002/hipo.22697
Manahan-Vaughan D, Reymann KG, Brown RE (1998) In vivo electrophysiological investigations into the role of histamine in the dentate gyrus of the rat. Neuroscience 84(3):783–790. https://doi.org/10.1016/S0306-4522(97)00540-X
Martin SJ, Grimwood PD, Morris RGM (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711
Martinez-Mir MI, Pollard H, Moreau J, Arrang JM, Ruat M, Traiffort E, Schwartz JC, Palacios JM (1990) Three histamine receptors (H1, H2 and H3) visualized in the brain of human and non-human primates. Brain Res 526(2):322–327
Masini D, Lopes-Aguiar C, Bonito-Oliva A, Papadia D, Andersson R, Fisahn A, Fisone G (2017) The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism. Transl Psychiatry 7(4):e1088–e1089. https://doi.org/10.1038/tp.2017.58
Masuoka T, Ikeda R, Konishi S (2019) Persistent activation of histamine H 1 receptors in the hippocampal CA1 region enhances NMDA receptor-mediated synaptic excitation and long-term potentiation in astrocyte- and D-serine-dependent manner. Neuropharmacology 151:64–73. https://doi.org/10.1016/j.neuropharm.2019.03.036
Mazurkiewicz-Kwilecki IM, Nsonwah S (1989) Changes in the regional brain histamine and histidine levels in postmortem brains of Alzheimer patients. Can J Physiol Pharmacol 67(1):75–78. https://doi.org/10.1139/y89-013
McDonnell MD, Ward LM (2011) The benefits of noise in neural systems: bridging theory and experiment. Nat Rev Neurosci 12(7):415–426. https://doi.org/10.1038/nrn3061
Medhurst AD, Roberts JC, Lee J, Chen CPLH, Brown SH, Roman S, Lai MKP (2009) Characterization of histamine H 3 receptors in Alzheimer’s disease brain and amyloid over-expressing TASTPM mice. Br J Pharmacol 157(1):130–138. https://doi.org/10.1111/j.1476-5381.2008.00075.x
Meeter M, Eijsackers EV, Mulder JL (2006) Retrograde amnesia for autobiographical memories and public events in mild and moderate Alzheimer’s disease. J Clin Exp Neuropsychol 28:914–927
Michael NJ, Zigman JM, Williams KW, Elmquist JK (2020) Electrophysiological properties of genetically identified histaminergic neurons. Neuroscience 444:183–195. https://doi.org/10.1016/j.neuroscience.2020.06.031
Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250
Molina-Hernández A, Velasco I (2008) Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors. J Neurochem 106(2):706–717. https://doi.org/10.1111/j.1471-4159.2008.05424.x
MondragĂłn-RodrĂguez S, Gu N, Manseau F, Williams S (2018) Alzheimer’s transgenic model is characterized by very early brain network alterations and β-CTF fragment accumulation: reversal by β-secretase inhibition. Front Cell Neurosci 12:121. https://doi.org/10.3389/fncel.2018.00121
Moriwaki C, Chiba S, Wei H, Aosa T, Kitamura H, Ina K, Shibata H, Fujikura Y (2015) Distribution of histaminergic neuronal cluster in the rat and mouse hypothalamus. J Chem Neuroanat 68:1–13. https://doi.org/10.1016/j.jchemneu.2015.07.001
Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12(2):120–150. https://doi.org/10.1038/sj.mp.4001939
Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406(6797):722–726. https://doi.org/10.1038/35021052
Naganuma F, Nakamura T, Yoshikawa T, Iida T, Miura Y, Kárpáti A, Matsuzawa T, Yanai A, Mogi A, Mochizuki T, Okamura N, Yanai K (2017) Histamine N-methyltransferase regulates aggression and the sleep-wake cycle. Sci Rep 7(1). https://doi.org/10.1038/s41598-017-16019-8
Nakayama D, Yamasaki Y, Matsuki N, Nomura H (2013) Post-retrieval late process contributes to persistence of reactivated fear memory. Learn Mem 20(6):307–310. https://doi.org/10.1101/lm.029660.112
Nakayama D, Baraki Z, Onoue K, Ikegaya Y, Matsuki N, Nomura H (2014) Frontal association cortex is engaged in stimulus integration during associative learning. Curr Biol 25(1):117–123. https://doi.org/10.1016/j.cub.2014.10.078
Nakayama D, Iwata H, Teshirogi C, Ikegaya Y, Matsuki N, Nomura H (2015) Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal circuits to perpetuate fear memory. J Neurosci 35(2):819–830. https://doi.org/10.1523/JNEUROSCI.2525-14.2015
Nakayama D, Hashikawa-Yamasaki Y, Ikegaya Y, Matsuki N, Nomura H, Nomura H (2016) Late Arc/Arg3.1 expression in the basolateral amygdala is essential for persistence of newly-acquired and reactivated contextual fear memories. Sci Rep 6(1):21007. https://doi.org/10.1038/srep21007
Nathan PJ, Boardley R, Scott N, Berges A, Maruff P, Sivananthan T, Upton N, Lowy MT, Nestor PJ, Lai R (2013) The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H3 receptor antagonist in patients with mild to moderate Alzheimer’s disease: a preliminary investigation. Curr Alzheimer Res 10(3):240–251. https://doi.org/10.2174/1567205011310030003
Nautiyal KM, McKellar H, Silverman AJ, Silver R (2009) Mast cells are necessary for the hypothermic response to LPS-induced sepsis. Am J Physiol Regul Integr Comp Physiol 296(3). https://doi.org/10.1152/ajpregu.90888.2008
Neves G, Cooke SF, Bliss TVP (2008) Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 9:65–75
Nishiga M, Fujii Y, Konishi M, Hossen MA (2003) Effects of second-generation histamine H1 receptor antagonists on the active avoidance response in rats. Clin Exp Pharmacol Physiol 30(1–2):60–63
Nomura H, Matsuki N (2008) Ethanol enhances reactivated fear memories. Neuropsychopharmacology 33(12):2912–2921. https://doi.org/10.1038/npp.2008.13
Nomura H, Nonaka A, Imamura N, Hashikawa K, Matsuki N (2012) Memory coding in plastic neuronal subpopulations within the amygdala. NeuroImage 60(1):153–161. https://doi.org/10.1016/j.neuroimage.2011.12.022
Nomura H, Mizuta H, Norimoto H, Masuda F, Miura Y, Kubo A, Kojima H, Ashizuka A, Matsukawa N, Baraki Z, Hitora-Imamura N, Nakayama D, Ishikawa T, Okada M, Orita K, Saito R, Yamauchi N, Sano Y, Kusuhara H, Minami M, Takahashi H, Ikegaya Y (2019) Central histamine boosts perirhinal cortex activity and restores forgotten object memories. Biol Psychiatry 86(3):230–239. https://doi.org/10.1016/j.biopsych.2018.11.009
Nonaka A, Masuda F, Nomura H, Matsuki N (2013) Impairment of fear memory consolidation and expression by antihistamines. Brain Res 1493:19–26. https://doi.org/10.1016/j.brainres.2012.11.030
Nonaka A, Toyoda T, Miura Y, Hitora-Imamura N, Naka M, Eguchi M, Yamaguchi S, Ikegaya Y, Matsuki N, Nomura H (2014) Synaptic plasticity associated with a memory engram in the basolateral amygdala. J Neurosci 34(28):9305–9309. https://doi.org/10.1523/JNEUROSCI.4233-13.2014
Oh J, Eser RA, Ehrenberg AJ, Morales D, Petersen C, Kudlacek J, Dunlop SR, Theofilas P, Resende EDPF, Cosme C, Alho EJL, Spina S, Walsh CM, Miller BL, Seeley WW, Bittencourt JC, Neylan TC, Heinsen H, Grinberg LT (2019) Profound degeneration of wake-promoting neurons in Alzheimer’s disease. Alzheimers Dement 15(10):1253–1263. https://doi.org/10.1016/j.jalz.2019.06.3916
Orsetti M, Ghi P, Di Carlo G (2001) Histamine H3-receptor antagonism improves memory retention and reverses the cognitive deficit induced by scopolamine in a two-trial place recognition task. Behav Brain Res 124(2):235–242
Panula P, Nuutinen S (2013) The histaminergic network in the brain: basic organization and role in disease. Nat Rev Neurosci 14(7):472–487. https://doi.org/10.1038/nrn3526
Panula P, Rinne J, Kuokkanen K, Eriksson KS, Sallmen T, Kalimo H, Relja M (1997) Neuronal histamine deficit in Alzheimer’s disease. Neuroscience 82(4):993–997. https://doi.org/10.1016/S0306-4522(97)00353-9
Pascoli V, Boer-Saccomani C, Hermant J-F (2009) H3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval. Psychopharmacology 202(1–3):141–152. https://doi.org/10.1007/s00213-008-1171-2
Passani MB, Cangioli I, Baldi E, Bucherelli C, Mannaioni PF, Blandina P (2001) Histamine H3 receptor-mediated impairment of contextual fear conditioning and in-vivo inhibition of cholinergic transmission in the rat basolateral amygdala. Eur J Neurosci 14(9):1522–1532. https://doi.org/10.1046/j.0953-816X.2001.01780.x
Payne GW, Neuman RS (1997) Effects of hypomagnesia on histamine H1 receptor-mediated facilitation of NMDA responses. Br J Pharmacol 121(2):199–204. https://doi.org/10.1038/sj.bjp.0701123
Pedarzani P, Storm JF (1995) Protein kinase A-independent modulation of ion channels in the brain by cyclic AMP. Proc Natl Acad Sci U S A 92(25):11716–11720. https://doi.org/10.1073/pnas.92.25.11716
Perry E, Court J, Goodchild R, Griffiths M, Jaros E, Johnson M, Lloyd S, Piggott M, Spurden D, Ballard C, McKeith I, Perry R (1998) Clinical neurochemistry: developments in dementia research based on brain bank material. J Neural Transm 105(8–9):915–933. https://doi.org/10.1007/s007020050102
Prast H, Argyriou A, Philippu A (1996) Histaminergic neurons facilitate social memory in rats. Brain Res 734(1–2):316–318
Provensi G, Costa A, Izquierdo I, Blandina P, Passani MB (2020) Brain histamine modulates recognition memory: possible implications in major cognitive disorders. Br J Pharmacol 177:539–556
Reijmers LG, Perkins BL, Matsuo N, Mayford M (2007) Localization of a stable neural correlate of associative memory. Science 317(5842):1230–1233. https://doi.org/10.1126/science.1143839
Reiner PB, Kamondi A (1994) Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current. Neuroscience 59(3):579–588. https://doi.org/10.1016/0306-4522(94)90178-3
Reiner PB, McGeer EG (1987) Electrophysiological properties of cortically projecting histamine neurons of the rat hypothalamus. Neurosci Lett 73(1):43–47. https://doi.org/10.1016/0304-3940(87)90028-0
Resendez SL, Jennings JH, Ung RL, Namboodiri VMK, Zhou ZC, Otis JM, Nomura H, McHenry JA, Kosyk O, Stuber GD (2016) Visualization of cortical, subcortical and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses. Nat Protoc 11(3):566–597. https://doi.org/10.1038/nprot.2016.021
Rizk A, Curley J, Robertson J, Raber J (2004) Anxiety and cognition in histamine H3 receptor-/- mice. Eur J Neurosci 19(7):1992–1996. https://doi.org/10.1111/j.1460-9568.2004.03251.x
RodrĂguez-MartĂnez G, Velasco I, GarcĂa-LĂłpez G, SolĂs KH, Flores-Herrera H, DĂaz NF, Molina-Hernández A (2012) Histamine is required during neural stem cell proliferation to increase neuron differentiation. Neuroscience 216:10–17. https://doi.org/10.1016/j.neuroscience.2012.04.049
Rossato JI, Bevilaqua LRM, Izquierdo I, Medina JH, Cammarota M (2009) Dopamine controls persistence of long-term memory storage. Science 325(5943):1017–1020. https://doi.org/10.1126/science.1172545
Ryan TJ, Roy DS, Pignatelli M, Arons A, Tonegawa S (2015) Memory. Engram cells retain memory under retrograde amnesia. Science 348(6238):1007–1013. https://doi.org/10.1126/science.aaa5542
Sadek B, Saad A, Sadeq A, Jalal F, Stark H (2016) Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases. Behav Brain Res 312:415–430
Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Shinichi A, Inoue Y, Sugiyama H, Mishina M (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit. Nature 373:151–155
Sanna MD, Ghelardini C, Thurmond RL, Masini E, Galeotti N (2017) Behavioural phenotype of histamine H4 receptor knockout mice: focus on central neuronal functions. Neuropharmacology 114:48–57. https://doi.org/10.1016/j.neuropharm.2016.11.023
Schlicker E, Kathmann M, Detzner M, Exner HJ, Göthert M (1994) H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase. Naunyn Schmiedeberg’s Arch Pharmacol 350(1):34–41
Schwartz J-C (2011) The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol 163(4):713–721. https://doi.org/10.1111/j.1476-5381.2011.01286.x
Selbach O, Brown RE, Haas HL (1997) Long-term increase of hippocampal excitability by histamine and cyclic AMP. Neuropharmacology 36(11–12):1539–1548. https://doi.org/10.1016/S0028-3908(97)00144-5
Sergeeva OA, Eriksson KS, Sharonova IN, Vorobjev VS, Haas HL (2002) GABAA receptor heterogeneity in histaminergic neurons. Eur J Neurosci 16(8):1472–1482. https://doi.org/10.1046/j.1460-9568.2002.02221.x
Shan L, Bossers K, Unmehopa U, Bao AM, Swaab DF (2012) Alterations in the histaminergic system in Alzheimer’s disease: a postmortem study. Neurobiol Aging 33(11):2585–2598. https://doi.org/10.1016/j.neurobiolaging.2011.12.026
Shan L, Bao AM, Swaab DF (2017) Changes in histidine decarboxylase, histamine n-methyltransferase and histamine receptors in neuropsychiatric disorders. Handb Exp Pharmacol 241:259–276
Shen H, Igarashi H, Imamura N, Matsuki N, Nomura H (2013) N-methyl-D-aspartate receptors and protein synthesis are necessary for reinstatement of conditioned fear. Neuroreport 24(14):763–767. https://doi.org/10.1097/WNR.0b013e328363b36c
Stevens DR, Eriksson KS, Brown RE, Haas HL (2001) The mechanism of spontaneous firing in histamine neurons. Behav Brain Res 124(2):105–112
Strakhova MI, Nikkel AL, Manelli AM, Hsieh GC, Esbenshade TA, Brioni JD, Bitner RS (2009) Localization of histamine H4 receptors in the central nervous system of human and rat. Brain Res 1250:41–48. https://doi.org/10.1016/j.brainres.2008.11.018
Strecker RE, Nalwalk J, Dauphin LJ, Thakkar MM, Chen Y, Ramesh V, Hough LB, McCarley RW (2002) Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: an in vivo microdialysis study. Neuroscience 113(3):663–670. https://doi.org/10.1016/S0306-4522(02)00158-6
Takeshita Y, Watanabe T, Sakata T, Munakata M, Ishibashi H, Akaike N (1998) Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. Neuroscience 87(4):797–805. https://doi.org/10.1016/S0306-4522(98)00152-3
Tarder-Stoll H, Jayakumar M, Dimsdale-Zucker HR, GĂĽnseli E, Aly M (2020) Dynamic internal states shape memory retrieval. Neuropsychologia 138:107328. https://doi.org/10.1016/j.neuropsychologia.2019.107328
Thomas SA (2015) Neuromodulatory signaling in hippocampus-dependent memory retrieval. Hippocampus 25(4):415–431. https://doi.org/10.1002/hipo.22394
Tonegawa S, Pignatelli M, Roy DS, Ryan TJ (2015) Memory engram storage and retrieval. Curr Opin Neurobiol 35:101–109. https://doi.org/10.1016/J.CONB.2015.07.009
Tonegawa S, Morrissey MD, Kitamura T (2018) The role of engram cells in the systems consolidation of memory. Nat Rev Neurosci 19(8):485–498. https://doi.org/10.1038/s41583-018-0031-2
Umehara H, Mizuguchi H, Mizukawa N, Matsumoto M, Takeda N, Senba E, Fukui H (2010) Innervation of histamine neurons in the caudal part of the arcuate nucleus of hypothalamus and their activation in response to food deprivation under scheduled feeding. Methods Find Exp Clin Pharmacol 32(10):733–736. https://doi.org/10.1358/mf.2010.32.10.1545781
Umehara H, Mizuguchi H, Mizukawa N, Matsumoto M, Takeda N, Senba E, Fukui H (2011) Deprivation of anticipated food under scheduled feeding induces c-Fos expression in the caudal part of the arcuate nucleus of hypothalamus through histamine H1 receptors in rats: potential involvement of E3 subgroup of histaminergic neurons in tuberomammillary nucleus. Brain Res 1387:61–70. https://doi.org/10.1016/j.brainres.2011.02.018
Umehara H, Mizuguchi H, Fukui H (2012) Identification of a histaminergic circuit in the caudal hypothalamus: an evidence for functional heterogeneity of histaminergic neurons. Neurochem Int 61(6):942–947
ValdĂ©s JL, FarĂas P, Ocampo-GarcĂ©s A, CortĂ©s N, SerĂłn-FerrĂ© M, Torrealba F (2005) Arousal and differential Fos expression in histaminergic neurons of the ascending arousal system during a feeding-related motivated behaviour. Eur J Neurosci 21(7):1931–1942. https://doi.org/10.1111/j.1460-9568.2005.04013.x
ValdĂ©s JL, Sánchez C, Riveros ME, Blandina P, Contreras M, FarĂas P, Torrealba F (2010) The histaminergic tuberomammillary nucleus is critical for motivated arousal. Eur J Neurosci 31(11):2073–2085. https://doi.org/10.1111/j.1460-9568.2010.07241.x
Van Deursen JA, Vuurman EFPM, Verhey FRJ, Van Kranen-Mastenbroek VHJM, Riedel WJ (2008) Increased EEG gamma band activity in Alzheimer’s disease and mild cognitive impairment. J Neural Transm 115(9):1301–1311. https://doi.org/10.1007/s00702-008-0083-y
van Ruitenbeek P, Mehta MA (2013) Potential enhancing effects of histamine H 1 agonism/H 3 antagonism on working memory assessed by performance and bold response in healthy volunteers. Br J Pharmacol 170(1):144–155. https://doi.org/10.1111/bph.12184
Vanni-Mercier G, Gigout S, Debilly G, Lin JS (2003) Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats. Behav Brain Res 144(1–2):227–241. https://doi.org/10.1016/S0166-4328(03)00091-3
Vazdarjanova A, McGaugh JL (1999) Basolateral amygdala is involved in modulating consolidation of memory for classical fear conditioning. J Neurosci 19(15):6615–6622
Vorobjev VS, Sharonova IN, Walsh IB, Haas HL (1993) Histamine potentiates N-methyl-d-aspartate responses in acutely isolated hippocampal neurons. Neuron 11(5):837–844. https://doi.org/10.1016/0896-6273(93)90113-6
Vorobjev VS, Sharonova IN, Haas HL, Sergeeva OA (2003) Expression and function of P2X purinoceptors in rat histaminergic neurons. Br J Pharmacol 138(5):1013–1019. https://doi.org/10.1038/sj.bjp.0705144
Wada H, Inagaki N, Yamatodani A, Watanabe T (1991) Is the histaminergic neuron system a regulatory center for whole-brain activity? Trends Neurosci 14(9):415–418
Wasielewska JM, Grönnert L, Rund N, Donix L, Rust R, Sykes AM, Hoppe A, Roers A, Kempermann G, Walker TL (2017) Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions. Sci Rep 7(1):1–13. https://doi.org/10.1038/s41598-017-18184-2
Westmacott R, Leach L, Freedman M, Moscovitch M (2001) Different patterns of autobiographical memory loss in semantic dementia and medial temporal lobe amnesia: a challenge to consolidation theory. Neurocase 7(1):37–55. https://doi.org/10.1093/neucas/7.1.37
Williams RH, Chee MJS, Kroeger D, Ferrari LL, Maratos-Flier E, Scammell TE, Arrigoni E (2014) Optogenetic-mediated release of histamine reveals distal and autoregulatory mechanisms for controlling arousal. J Neurosci 34(17):6023–6029. https://doi.org/10.1523/JNEUROSCI.4838-13.2014
Xu LS, Yang LX, Hu WW, Yu X, Ma L, Liu LY, Wei EQ, Chen Z (2005) Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats. Acta Pharmacol Sin 26(12):1448–1453. https://doi.org/10.1111/j.1745-7254.2005.00229.x
Yamada Y, Yoshikawa T, Naganuma F, Kikkawa T, Osumi N, Yanai K (2020) Chronic brain histamine depletion in adult mice induced depression-like behaviours and impaired sleep-wake cycle. Neuropharmacology 175:108179. https://doi.org/10.1016/j.neuropharm.2020.108179
Yamakami J, Sakurai E, Kuramasu A, Sakurai E, Yanai K, Watanabe T, Tanaka Y (2000) L-Histidine decarboxylase protein and activity in rat brain microvascular endothelial cells. Inflamm Res 49(5):231–235. https://doi.org/10.1007/s000110050584
Yamamoto Y, Mochizuki T, Okakura-Mochizuki K, Uno A, Yamatodani A (1997) Thioperamide, a histamine H3 receptor antagonist, increases GABA release from the rat hypothalamus. Methods Find Exp Clin Pharmacol 19(5):289–298
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660
Zheng C, Bieri KW, Hsiao YT, Colgin LL (2016) Spatial sequence coding differs during slow and fast gamma rhythms in the hippocampus. Neuron 89(2):398–408. https://doi.org/10.1016/j.neuron.2015.12.005
Zlomuzica A, Ruocco LA, Sadile AG, Huston JP, Dere E (2009) Histamine H 1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze. Br J Pharmacol 157(1):86–91. https://doi.org/10.1111/j.1476-5381.2009.00225.x
Zlomuzica A, Dere D, Binder S, De Souza Silva MA, Huston JP, Dere E (2016) Neuronal histamine and cognitive symptoms in Alzheimer’s disease. Neuropharmacology 106:135–145
Acknowledgments
This work was partly supported by grants from JSPS KAKENHI (No. 20H03551 to HN and No. 20K21557 to HN) and MEXT KAKENHI (No. 20H05045 to HN and No. 21H00296 to HN).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Nomura, H., Shimizume, R., Ikegaya, Y. (2021). Histamine: A Key Neuromodulator of Memory Consolidation and Retrieval. In: Yanai, K., Passani, M.B. (eds) The Functional Roles of Histamine Receptors. Current Topics in Behavioral Neurosciences, vol 59. Springer, Cham. https://doi.org/10.1007/7854_2021_253
Download citation
DOI: https://doi.org/10.1007/7854_2021_253
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-16996-0
Online ISBN: 978-3-031-16997-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)