Abstract
First described by Boissier and Simon in (Ther Recreat J 17:1225–1232, 1962), the hole-board has become a recognized test of anxiety and spatial memory. Benzodiazepines acting at the GABAA-BZD site increase hole-pokes in rats and mice, indicating a loss in behavioral inhibition concordant with the behavior of mutant mice deficient in the GABA transporter. Hole-poking also depends on arousal mechanisms dependent on dopaminergic transmission, as indicated by drug and null mutant studies. In addition, the behavior is modified in natural and null mutants affecting the cerebellum as well as null mutants affecting neuropeptides, growth factors, cell adhesion, and inflammation. Further research is required to determine convergences between genetic and pharmacological effects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
Not applicable.
Code Availability
Not applicable.
References
Adamec RE (1990) Amygdala kindling and anxiety in the rat. NeuroReport 1(3–4):255–258. https://doi.org/10.1097/00001756-199011000-00022 (PMID: 2129887)
Adamec RE, McKay D (1993) The effects of CRF and alpha-helical CRF on anxiety in normal and hypophysectomized rats. J Psychopharmacol 7(4):346–354. https://doi.org/10.1177/026988119300700406 (PMID: 22290998)
Anlar B, Gunel-Ozcan A (2012) Tenascin-R: role in the central nervous system. Int J Biochem Cell Biol 44(9):1385–1389. https://doi.org/10.1016/j.biocel.2012.05.009 (PMID: 22634605)
Armario A, Hernández J, Bluethmann H, Hidalgo J (1998) IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6. J Neuroimmunol 92(1–2):160–169. https://doi.org/10.1016/s0165-5728(98)00199-4 (PMID: 9916891)
Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J, Tsao MS, Shannon P, Bolon B, Ivy GO, Mak TW (2001) Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 29(4):396–403. https://doi.org/10.1038/ng782 (PMID: 11726926)
Bannerman DM, Yee BK, Good MA, Heupel MJ, Iversen SD, Rawlins JN (1999) Double dissociation of function within the hippocampus: a comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions. Behav Neurosci 113(6):1170–1188. https://doi.org/10.1037//0735-7044.113.6.1170 (PMID: 10636297)
Barrett DW, Gonzalez-Lima F (2018) Prefrontal-limbic functional connectivity during acquisition and extinction of conditioned fear. Neuroscience 376:162–171. https://doi.org/10.1016/j.neuroscience.2018.02.022 (PMID: 29477695)
Becker A, Eyles DW, McGrath JJ, Grecksch G (2005) Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav Brain Res 161(2):306–312. https://doi.org/10.1016/j.bbr.2005.02.015 (PMID: 15922058)
Bialuk I, Winnicka MM (2018) Facilitatory effect of IL-6 deficiency on long-term spatial memory in young adult mice. Behav Genet 48(3):236–246. https://doi.org/10.1007/s10519-018-9896-0 (PMID: 29619678)
Bilkei-Gorzó A, Gyertyán I (1996) Some doubts about the basic concept of hole-board test. Neurobiology (bp) 4(4):405–415 (PMID: 9200132)
Boissier JR, Simon P (1962) La réaction d’exploration chez la souris. Ther Recreat J 17:1225–1232 (PMID: 13968530)
Bortolato M, Godar SC, Davarian S, Chen K, Shih JC (2009) Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice. Neuropsychopharmacology 34(13):2746–2757. https://doi.org/10.1038/npp.2009.118 (PMID: 19710633)
Brown GR, Nemes C (2008) The exploratory behaviour of rats in the hole-board apparatus: is head-dipping a valid measure of neophilia? Behav Proc 78(3):442–448. https://doi.org/10.1016/j.beproc.2008.02.019 (PMID: 18406075)
Burne TH, McGrath JJ, Eyles DW, Mackay-Sim A (2005) Behavioural characterization of vitamin D receptor knockout mice. Behav Brain Res 157(2):299–308. https://doi.org/10.1016/j.bbr.2004.07.008 (PMID: 15639181)
Burne TH, Becker A, Brown J, Eyles DW, Mackay-Sim A, McGrath JJ (2004) Transient prenatal vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav Brain Res 154(2):549–555. https://doi.org/10.1016/j.bbr.2004.03.023 (PMID: 15313044)
Canovas R, Espínola M, Iribarne L, Cimadevilla JM (2008) A new virtual task to evaluate human place learning. Behav Brain Res 190(1):112–118. https://doi.org/10.1016/j.bbr.2008.02.024 (PMID: 18374426)
Castilla-Ortega E, Hoyo-Becerra C, Pedraza C, Chun J, Rodríguez De Fonseca F, Estivill-Torrús G, Santín LJ (2011) Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA1 receptor knockout mice. PLoS ONE 6(9):e25522. https://doi.org/10.1371/journal.pone.0025522 (PMID: 21980482)
Castilla-Ortega E, Sánchez-López J, Hoyo-Becerra C, Matas-Rico E, Zambrana-Infantes E, Chun J, De Fonseca FR, Pedraza C, Estivill-Torrús G, Santin J (2010) Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor. Neurobiol Learn Mem 94(1):73–82. https://doi.org/10.1016/j.nlm.2010.04.003 (PMID: 20388543)
Catts VS, Al-Menhali N, Burne TH, Colditz MJ, Coulson EJ (2008) The p75 neurotrophin receptor regulates hippocampal neurogenesis and related behaviours. Eur J Neurosci 28(5):883–892. https://doi.org/10.1111/j.1460-9568.2008.06390.x (PMID: 18717734)
Chari T, Griswold S, Andrews NA, Fagiolini M (2020) The stage of the estrus cycle is critical for interpretation of female mouse social interaction behavior. Front Behav Neurosci 14:113. https://doi.org/10.3389/fnbeh.2020.00113 (PMID: 32714163)
Cho YH, Jeantet Y (2010) Differential involvement of prefrontal cortex, striatum, and hippocampus in DRL performance in mice. Neurobiol Learn Mem 93(1):85–91. https://doi.org/10.1016/j.nlm.2009.08.007 (PMID: 19703576)
Choi JW (2013) Chun J (2013) Lysophospholipids and their receptors in the central nervous system. Biochim Biophys Acta 1:20–32. https://doi.org/10.1016/j.bbalip.2012.07.015 (PMID: 22884303)
Colombel C, Lalonde R, Caston J (2002) The effects of unilateral removal of the cerebellar hemispheres on motor functions and weight gain in rats. Brain Res 950(1–2):231–238. https://doi.org/10.1016/s0006-8993(02)03043-3 (PMID: 12231248)
Crawley JN (1985) Exploratory behavior models of anxiety in mice. Neurosci Biobehav Rev 9(1):37–44. https://doi.org/10.1016/0149-7634(85)90030-2 (PMID: 2858080)
Deacon CF (2019) Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol (lausanne) 10:80. https://doi.org/10.3389/fendo.2019.00080 (PMID: 30828317)
Dean P, Redgrave P (1983) Head-dipping by rats with lesions of superior colliculus during extended testing in hole-board. Behav Brain Res 8(3):309–316. https://doi.org/10.1016/0166-4328(83)90176-6 (PMID: 6871016)
Devauges V, Sara SJ (1990) Activation of the noradrenergic system facilitates an attentional shift in the rat. Behav Brain Res 39(1):19–28. https://doi.org/10.1016/0166-4328(90)90118-x (PMID: 2167690)
Durán E, Ocaña FM, Martín-Monzón I, Rodríguez F, Salas C (2014) Cerebellum and spatial cognition in goldfish. Behav Brain Res 259:1–8. https://doi.org/10.1016/j.bbr.2013.10.039 (PMID: 24184084)
Durán E, Ocaña FM, Broglio C, Rodríguez F, Salas C (2010) Lateral but not medial telencephalic pallium ablation impairs the use of goldfish spatial allocentric strategies in a “hole-board” task. Behav Brain Res 214(2):480–487. https://doi.org/10.1016/j.bbr.2010.06.010 (PMID: 20600353)
Eltokhi A, Kurpiers B, Pitzer C (2020) Behavioral tests assessing neuropsychiatric phenotypes in adolescent mice reveal strain- and sex-specific effects. Sci Rep 10(1):11263. https://doi.org/10.1038/s41598-020-67758-0 (PMID: 32647155)
El Yacoubi M, Vaugeois JM, Marguet D, Sauze N, Guieu R, Costentin J, Fenouillet E (2006) Behavioral characterization of CD26 deficient mice in animal tests of anxiety and antidepressant-like activity. Behav Brain Res 171(2):279–285. https://doi.org/10.1016/j.bbr.2006.04.003 (PMID: 16712972)
Erhardt A, Müller MB, Rödel A, Welt T, Ohl F, Holsboer F, Keck ME (2009) Consequences of chronic social stress on behaviour and vasopressin gene expression in the PVN of DBA/2OlaHsd mice- influence of treatment with the CRHR1-antagonist R121919/NBI 30775. J Psychopharmacol 23(1):31–39. https://doi.org/10.1177/0269881108089813 (PMID: 18515457)
Erta M, Giralt M, Esposito FL, Fernandez-Gayol O, Hidalgo J (2015) Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior. Horm Behav 73:64–74. https://doi.org/10.1016/j.yhbeh.2015.06.016 (PMID: 26143620)
File SE (1982) The rat corticosterone response: habituation and modification by chlordiazepoxide. Physiol Behav 29(1):91–95. https://doi.org/10.1016/0031-9384(82)90371-7 (PMID: 7122741)
File SE (1978) ACTH, but not corticosterone impairs habituation and reduces exploration. Pharmacol Biochem Behav 9(2):161–166. https://doi.org/10.1016/0091-3057(78)90159-4 (PMID: 213788)
File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia 44(1):53–59. https://doi.org/10.1007/BF00421184 (PMID: 1197580)
Fiore M, Alleva E, Probert L, Kollias G, Angelucci F, Aloe L (1998) Exploratory and displacement behavior in transgenic mice expressing high levels of brain TNF-alpha. Physiol Behav 63(4):571–576. https://doi.org/10.1016/s0031-9384(97)00514-3 (PMID: 9523900)
Florin S, Suaudeau C, Meunier JC, Costentin J (1996) Nociceptin stimulates locomotion and exploratory behaviour in mice. Eur J Pharmacol 317(1):9–13. https://doi.org/10.1016/s0014-2999(96)00707-8 (PMID: 8982713)
Foreman JE, Lionikas A, Lang DH, Gyekis JP, Krishnan M, Sharkey NA, Gerhard GS, Grant MD, Vogler GP, Mack HA, Stout JT, Griffith JW, Lakoski JM, Hofer SM, McClearn GE, Vandenbergh DJ, Blizard DA (2009) Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice. Genes Brain Behav 8(7):714–727. https://doi.org/10.1111/j.1601-183X.2009.00516.x (PMID: 19671078)
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M (2021) Alzheimer’s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol 20(11):930–942. https://doi.org/10.1016/S1474-4422(21)00245-3 (PMID: 34687637)
Fox KM, Sterling RC, Van Bockstaele EJ (2009) Cannabinoids and novelty investigation: influence of age and duration of exposure. Behav Brain Res 196(2):248–253. https://doi.org/10.1016/j.bbr.2008.09.033 (PMID: 18951925)
Gandhi CC, Kelly RM, Wiley RG, Walsh TJ (2000) Impaired acquisition of a Morris water maze task following selective destruction of cerebellar purkinje cells with OX7-saporin. Behav Brain Res 109(1):37–47. https://doi.org/10.1016/s0166-4328(99)00160-6 (PMID: 10699656)
Gao J, Li K, Du L, Yin H, Tan X, Yang Z (2018) Deletion of asparagine endopeptidase reduces anxiety- and depressive-like behaviors and improves abilities of spatial cognition in mice. Brain Res Bull 142:147–155. https://doi.org/10.1016/j.brainresbull.2018.07.010 (PMID: 30030107)
Gavioli EC, Rizzi A, Marzola G, Zucchini S, Regoli D, Calo’ G (2007) Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout mice. Peptides 28(6):1229–1239. https://doi.org/10.1016/j.peptides.2007.04.012 (PMID: 17499882)
Geraldo LHM, Spohr TCLS, Amaral RFD, Fonseca ACCD, Garci C, Mendes FA, Freitas C, dosSantos MF, Lima FRS (2021) Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies. Signal Transduct Target Ther 6(1):45. https://doi.org/10.1038/s41392-020-00367-5 (PMID: 33526777)
Gimenez-Llort L, Fernández-Teruel A, Escorihuela RM, Fredholm BB, Tobeña A, Pekny M, Johansson B (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16(3):547–550. https://doi.org/10.1046/j.1460-9568.2002.02122.x (PMID: 12193199)
Goes TC, Almeida Souza TH, Marchioro M, Teixeira-Silva F (2018) Excitotoxic lesion of the medial prefrontal cortex in Wistar rats: effects on trait and state anxiety. Brain Res Bull 142:313–319. https://doi.org/10.1016/j.brainresbull.2018.08.009 (PMID: 30120930)
Goodlett CR, Hamre KM, West JR (1992) Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice. Behav Brain Res 47(2):129–141. https://doi.org/10.1016/s0166-4328(05)80119-6 (PMID: 1590945)
Grootendorst J, de Kloet ER, Vossen C, Dalm S, Oitzl MS (2001) Repeated exposure to rats has persistent genotype-dependent effects on learning and locomotor activity of apolipoprotein E knockout and C57Bl/6 mice. Behav Brain Res 125(1–2):249–259. https://doi.org/10.1016/s0166-4328(01)00294-7 (PMID: 11682116)
Ha S, Lee D, Cho YS, Chung C, Yoo YE, Kim J, Lee J, Kim W, Kim H, Bae YC, Tanaka-Yamamoto K, Kim E (2016) Cerebellar Shank2 regulates excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. J Neurosci 36(48):12129–12143. https://doi.org/10.1523/JNEUROSCI.1849-16.2016 (PMID: 27903723)
Harms LR, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH (2008) Developmental vitamin D deficiency alters adult behaviour in 129/SvJ and C57BL/6J mice. Behav Brain Res 187(2):343–350. https://doi.org/10.1016/j.bbr.2007.09.032 (PMID: 17996959)
Havas D, Hutter-Paier B, Ubhi K, Rockenstein E, Crailsheim K, Masliah E, Windisch M (2011) A longitudinal study of behavioral deficits in an AβPP transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 25(2):231–243. https://doi.org/10.3233/JAD-2011-101866 (PMID: 21403389)
Hernández-Tristán R, Leret ML, Almeida D (2006) Effect of intrauterine position on sex differences in the gabaergic system and behavior of rats. Physiol Behav 87(3):625–633. https://doi.org/10.1016/j.physbeh.2006.01.002 (PMID: 16478627)
Hilber P, Lalonde R, Caston J (1999) An unsteady platform test for measuring static equilibrium in mice. J Neurosci Methods 88(2):201–205. https://doi.org/10.1016/s0165-0270(99)00035-7 (PMID: 10389667)
Hobson BD, O’Neill CE, Levis SC, Monteggia LM, Neve RL, Self DW, Bachtell RK (2013) Adenosine A1 and dopamine D1 receptor regulation of AMPA receptor phosphorylation and cocaine-seeking behavior. Neuropsychopharmacology 38(10):1974–1983. https://doi.org/10.1038/npp.2013.96 (PMID: 23598433)
Hölscher C (2003) Time, space and hippocampal functions. Rev Neurosci 14(3):253–284. https://doi.org/10.1515/revneuro.2003.14.3.253 (PMID: 14513868)
Hranilovic D, Bucan M, Wang Y (2008) Emotional response in dopamine D2L receptor-deficient mice. Behav Brain Res 195(2):246–250. https://doi.org/10.1016/j.bbr.2008.09.007 (PMID: 18835570)
Huang Y, Mahley RW (2014) Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases. Neurobiol Dis 72:3–12. https://doi.org/10.1016/j.nbd.2014.08.025 (PMID: 25173806)
Hulbert SW, Bey A, Jiang YH (2018) Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder. Brain Behav 8(11):e01107. https://doi.org/10.1002/brb3.1107 (PMID: 30317697)
d’Isa R, Comi G, Leocani L (2021) The 4-hole-board test for assessment of long-term spatial memory in mice. Curr Protoc 1(8):e228. https://doi.org/10.1002/cpz1.228 (PMID: 34432376)
Irizarry MC, Rebeck GW, Cheung B, Bales K, Paul SM, Holzman D, Hyman BT (2000) Modulation of A beta deposition in APP transgenic mice by an apolipoprotein E null background. Ann NY Acad Sci 920:171–178. https://doi.org/10.1111/j.1749-6632.2000.tb06919.x (PMID: 11193147)
Ishizuka Y, Abe H, Tanoue A, Kannan H, Ishida Y (2010) Involvement of vasopressin V1b receptor in anti-anxiety action of SSRI and SNRI in mice. Neurosci Res 66(3):233–237. https://doi.org/10.1016/j.neures.2009.11.004 (PMID: 19914307)
Jarrard LE, Becker JT (1977) The effects of selective hippocampal lesions on DRL behavior in rats. Behav Biol 21(3):393–404. https://doi.org/10.1016/s0091-6773(77)90191-2 (PMID: 921681)
Jarrard LE, Luu LP, Davidson TL (2012) A study of hippocampal structure-function relations along the septo-temporal axis. Hippocampus 22(4):680–692. https://doi.org/10.1002/hipo.20928 (PMID: 21538656)
Jeljeli M, Strazielle C, Caston J, Lalonde R (2003) Effects of ventrolateral-ventromedial thalamic lesions on motor coordination and spatial orientation in rats. Neurosci Res 47(3):309–316. https://doi.org/10.1016/s0168-0102(03)00224-4 (PMID: 14568112)
Jeljeli M, Strazielle C, Caston J, Lalonde R (2000) Effects of centrolateral or medial thalamic lesions on motor coordination and spatial orientation in rats. Neurosci Res 38(2):155–164. https://doi.org/10.1016/s0168-0102(00)00152-8 (PMID: 11000442)
Jeljeli M, Strazielle C, Caston J, Lalonde R (1999) Effects of electrolytic lesions of the lateral pallidum on motor coordination, spatial learning, and regional brain variations of cytochrome oxidase activity in rats. Behav Brain Res 102(1–2):61–71. https://doi.org/10.1016/s0166-4328(98)00162-4 (PMID: 10403016)
Johnson CT, Olton DS, Gage FH 3rd, Jenko PG (1977) Damage to hippocampus and hippocampal connections: effects on DRL and spontaneous alternation. J Comp Physiol Psychol 91(3):508–522. https://doi.org/10.1037/h0077346 (PMID: 874119)
Joyal CC, Beaudin S, Lalonde R (2000) Longitudinal age-related changes in motor activities and spatial orientation in CD-1 mice. Arch Physiol Biochem 108(3):248–256. https://doi.org/10.1076/1381345520000710831zft248 (PMID: 11094377)
Kalueff AV, Lou YR, Laaksi I, Tuohimaa P (2004) Increased grooming behavior in mice lacking vitamin D receptors. Physiol Behav 82(2–3):405–409. https://doi.org/10.1016/j.physbeh.2004.04.010 (PMID: 15276805)
Kamei J, Matsunawa Y, Miyata S, Tanaka S, Saitoh A (2004) Effects of nociceptin on the exploratory behavior of mice in the hole-board test. Eur J Pharmacol 489(1–2):77–87. https://doi.org/10.1016/j.ejphar.2003.12.020 (PMID: 15063158)
Karl T, Burne TH, Herzog H (2006) Effect of Y1 receptor deficiency on motor activity, exploration, and anxiety. Behav Brain Res 167(1):87–93. https://doi.org/10.1016/j.bbr.2005.08.019 (PMID: 16203045)
Kim YJ, Park S, Ha T, Kim S, Lim S, You H, Kim JW (2021) Retinoid metabolism in the degeneration of Pten-deficient mouse retinal pigment epithelium. Mol Cells 44(8):613–622. https://doi.org/10.14348/molcells.2021.0138 (PMID: 34376625)
Kirk WT, Berntson GG, Hothersall D (1982) Effects of paleocerebellar lesions on DRL performance in the albino rat. J Comp Physiol Psychol 96(3):348–360. https://doi.org/10.1037/h0077893 (PMID: 7096677)
Kliethermes CL, Crabbe JC (2006a) Genetic independence of mouse measures of some aspects of novelty seeking. Proc Natl Acad Sci USA 103(13):5018–5023. https://doi.org/10.1073/pnas.0509724103 (PMID: 16551746)
Kliethermes CL, Crabbe JC (2006b) Pharmacological and genetic influences on hole-board behaviors in mice. Pharmacol Biochem Behav 85(1):57–65. https://doi.org/10.1016/j.pbb.2006.07.007 (PMID: 16949140)
Laarakker MC, Ohl F, van Lith HA (2008) Chromosomal assignment of quantitative trait loci influencing modified hole board behavior in laboratory mice using consomic strains, with special reference to anxiety-related behavior and mouse chromosome 19. Behav Genet 38(2):159–184. https://doi.org/10.1007/s10519-007-9188-6 (PMID: 18175213)
Labots M, Laarakker MC, Ohl F, van Lith HA (2016) Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety-related behavior and locomotion. BMC Genet 17(1):95. https://doi.org/10.1186/s12863-016-0411-4 (PMID: 27357390)
Lacreuse A, Woods CE, Herndon JG (2007) Effects of aging and hormonal status on bimanual motor coordination in the rhesus monkey. Neurobiol Aging 28(2):186–193. https://doi.org/10.1016/j.neurobiolaging.2005.11.013 (PMID: 16413948)
Lalonde R (1987a) Motor abnormalities in staggerer mutant mice. Exp Brain Res 68(2):417–420. https://doi.org/10.1007/BF00248807 (PMID: 3691712)
Lalonde R (1987b) Motor abnormalities in weaver mutant mice. Exp Brain Res 65(2):479–481. https://doi.org/10.1007/BF00236322 (PMID: 3556474)
Lalonde R, Botez MI (1985a) Exploration and habituation in nervous mutant mice. Behav Brain Res 17(2):83–86. https://doi.org/10.1016/0166-4328(85)90020-8 (PMID: 4074492)
Lalonde R, Botez MI (1985b) Exploration of a hole-board matrix in nervous mutant mice. Brain Res 343(2):356–359. https://doi.org/10.1016/0006-8993(85)90755-3 (PMID: 4052756)
Lalonde R, Joyal CC (1993) Effects of ketamine and L-glutamic acid diethyl ester on spatial and nonspatial learning tasks in rats. Pharmacol Biochem Behav 44(3):539–545. https://doi.org/10.1016/0091-3057(93)90164-o (PMID: 8451257)
Lalonde R, Strazielle C (2019) Motor performances of spontaneous and genetically modified mutants with cerebellar atrophy. Cerebellum 18(3):615–634. https://doi.org/10.1007/s12311-019-01017-5 (PMID: 30820866)
Lalonde R, Strazielle C (2013) The effects of cerebellar damage on maze learning in animals. Cerebellum 2(4):300–309. https://doi.org/10.1080/14734220310017456 (PMID: 14964689)
Lalonde R, Manseau M, Botez MI (1989) Exploration and habituation in Purkinje cell degeneration mutant mice. Brain Res 479(1):201–203. https://doi.org/10.1016/0006-8993(89)91354-1 (PMID: 2924150)
Lalonde R, Manseau M, Botez MI (1988a) Spontaneous alternation and exploration in staggerer mutant mice. Behav Brain Res 27(3):273–276. https://doi.org/10.1016/0166-4328(88)90124-6 (PMID: 3358865)
Lalonde R, Manseau M, Botez MI (1988b) Spontaneous alternation and exploration in weaver mutant mice. Behav Brain Res 31(2):111–114. https://doi.org/10.1016/0166-4328(88)90013-7 (PMID: 3202943)
Lalonde R, Botez MI, Joyal CC, Caumartin M (1992) Motor abnormalities in lurcher mutant mice. Physiol Behav 51(3):523–525. https://doi.org/10.1016/0031-9384(92)90174-z (PMID: 1523229)
Lalonde R, Joyal CC, Guastavino JM, Botez MI (1993) Hole poking and motor coordination in lurcher mutant mice. Physiol Behav 54(1):41–44. https://doi.org/10.1016/0031-9384(93)90041-d (PMID: 8327607)
Lamberty Y, Gower AJ (1992) Age-related changes in spontaneous behavior and learning in NMRI mice from middle to old age. Physiol Behav 51(1):81–88. https://doi.org/10.1016/0031-9384(92)90206-h (PMID: 1741453)
Lardner AL (2015) Vitamin D and hippocampal development- the story so far. Front Mol Neurosci 8:58. https://doi.org/10.3389/fnmol.2015.00058 (PMID: 26468295)
Liu X, Si W, Garau C, Jüngling K, Pape HC, Schulz S, Reinscheid RK (2017) Neuropeptide S precursor knockout mice display memory and arousal deficits. Eur J Neurosci 46(1):1689–1700. https://doi.org/10.1111/ejn.13613 (PMID: 28548278)
Lister RG (1987) The effects of ethanol on exploration in DBA/2 and C57Bl/6 mice. Alcohol 4(1):17–19. https://doi.org/10.1016/0741-8329(87)90054-1 (PMID: 3828059)
Lugo JN, Smith GD, Arbuckle EP, White J, Holley AJ, Floruta CM, Ahmed N, Gomez MC, Okonkwo O (2014) Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins. Front Mol Neurosci 7:27. https://doi.org/10.3389/fnmol.2014.00027 (PMID: 24795561)
Makanjuola RO, Hill G, Dow RC, Campbell G, Ashcroft GW (1977) The effects of psychotropic drugs on exploratory and stereotyped behaviour of rats studied on a hole-board. Psychopharmacology 55(1):67–74. https://doi.org/10.1007/BF00432819 (PMID: 414263)
Manso Y, Carrasco J, Comes G, Meloni G, Adlard PA, Bush AI, Vašák M, Hidalgo J (2012) Characterization of the role of metallothionein-3 in an animal model of Alzheimer’s disease. Cell Mol Life Sci 69(21):3683–3700. https://doi.org/10.1007/s00018-012-1047-9 (PMID: 22722772)
Mansouri A, Min W, Cole CJ, Josselyn SA, Henderson JT, van Eede M, Henkelman RM, Ackerley C, Grunebaum E, Roifman CM (2012) Cerebellar abnormalities in purine nucleoside phosphorylase deficient mice. Neurobiol Dis 47(2):201–209. https://doi.org/10.1016/j.nbd.2012.04.001 (PMID: 22521465)
Marquez C, Nadal R, Armario A (2005) Responsiveness of the hypothalamic-pituitary-adrenal axis to different novel environments is a consistent individual trait in adult male outbred rats. Psychoneuroendocrinology 30(2):179–187. https://doi.org/10.1016/j.psyneuen.2004.05.012 (PMID: 15471615)
Martin LA, Goldowitz D, Mittleman G (2010) Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism. Eur J Neurosci 31(3):544–555. https://doi.org/10.1111/j.1460-9568.2009.07073.x (PMID: 20105240)
Martinez-Cué C, Baamonde C, Lumbreras M, Paz J, Davisson MT, Schmidt C, Dierssen M, Flórez J (2002) Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome. Behav Brain Res 134(1–2):185–200. https://doi.org/10.1016/s0166-4328(02)00026-8 (PMID: 12191805)
Matsumoto D, Ushio S, Wada Y, Noda Y, Esumi S, Izushi Y, Kitamura Y, Sendo T (2021) Bumetanide prevents diazepam-modified anxiety-like behavior in lipopolysaccharide-treated mice. Eur J Pharmacol 904:174195. https://doi.org/10.1016/j.ejphar.2021.174195 (PMID: 34004209)
Matsumoto Y, Katayama K, Okamoto T, Yamada K, Takashima N, Nagao S, Aruga J (2011) Impaired auditory-vestibular functions and behavioral abnormalities of Slitrk6-deficient mice. PLoS ONE 6(1):e16497. https://doi.org/10.1371/journal.pone.0016497 (PMID: 21298075)
Mesa-Gresa P, Ramos-Campos M, Redolat R (2021) Behavioral impact of experience based on environmental enrichment: Influence of age and duration of exposure in male NMRI mice. Dev Psychobiol 63(5):1071–1081. https://doi.org/10.1002/dev.22093 (PMID: 33452673)
Molinari M, Grammaldo LG, Petrosini L (1997) Cerebellar contribution to spatial event processing: right/left discrimination abilities in rats. Eur J Neurosci 9(9):1986–1992. https://doi.org/10.1111/j.1460-9568.1997.tb00766.x (PMID: 9383222)
Monnier C, Lalonde R (1995) Elevated (+)-maze and hole-board exploration in lurcher mutant mice. Brain Res 702(1–2):169–172. https://doi.org/10.1016/0006-8993(95)01036-5 (PMID: 8846072)
Montag-Sallaz M, Montag D (2003) Severe cognitive and motor coordination deficits in tenascin-R-deficient mice. Genes Brain Behav 2(1):20–31. https://doi.org/10.1034/j.1601-183x.2003.00003.x (PMID: 12882316)
Moore RY, Bloom FE (1978) Central catecholamine neuron systems: anatomy and physiology of the dopamine systems. Annu Rev Neurosci 1:129–169. https://doi.org/10.1146/annurev.ne.01.030178.001021 (PMID: 756202)
Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR, Xiao R, Kliewer SA (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol Rev 58(4):742–759. https://doi.org/10.1124/pr.58.4.6 (PMID: 17132852)
Morris RG, Steele RJ, Bell JE, Martin SJ (2013) N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning. Eur J Neurosci 37(5):700–717. https://doi.org/10.1111/ejn.12086 (PMID: 23311352)
Moy SS, Nadler JJ, Poe MD, Nonneman RJ, Young NB, Koller BH, Crawley JN, Duncan GE, Bodfish JW (2008) Development of a mouse test for repetitive, restricted behaviors: relevance to autism. Behav Brain Res 188(1):178–194. https://doi.org/10.1016/j.bbr.2007.10.029 (PMID: 18068825)
Mulvihill EE, Drucker DJ (2014) Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev 35(6):992–1019. https://doi.org/10.1210/er.2014-1035 (PMID: 25216328)
Neeman M (1986) The Purdue Pegboard: its predictive validity for work potential of persons with mental retardation. Am J Occup Ther 40(6):433–434. https://doi.org/10.5014/ajot.40.6.433c (PMID: 3717282)
Netrakanti PR, Cooper BH, Dere E, Poggi G, Winkler D, Brose N, Ehrenreich H (2015) Fast cerebellar reflex circuitry requires synaptic vesicle priming by munc13-3. Cerebellum 14(3):264–283. https://doi.org/10.1007/s12311-015-0645-0 (PMID: 25617111)
Noblett KL, Swain RA (2003) Pretraining enhances recovery from visuospatial deficit following cerebellar dentate nucleus lesion. Behav Neurosci 117(4):785–798. https://doi.org/10.1037/0735-7044.117.4.785 (PMID: 12931963)
Nolan NA, Parkes MW (1973) The effects of benzodiazepines on the behaviour of mice on a hole-board. Psychopharmacologia 29(3):277–286. https://doi.org/10.1007/BF00414043 (PMID: 4702279)
Oades RD (1981) Type of memory or attention? Impairments after lesions of the hippocampus and limbic ventral tegmentum. Brain Res Bull 7(2):221–226. https://doi.org/10.1016/0361-9230(81)90086-1 (PMID: 7272800)
Ognibene E, Bovicelli P, Adriani W, Saso L, Laviola G (2008) Behavioral effects of 6-bromoflavanone and 5-methoxy-6,8-dibromoflavanone as anxiolytic compounds. Prog Neuropsychopharmacol Biol Psychiatry 32(1):128–234. https://doi.org/10.1016/j.pnpbp.2007.07.023 (PMID: 17888554)
Ohl F, Holsboer F, Landgraf R (2001) The modified hole board as a differential screen for behavior in rodents. Behav Res Methods Instrum Comput 33(3):392–397. https://doi.org/10.3758/bf03195393 (PMID: 11591071)
Ponomareva NS, Voskresenskaya OG, Kamenskii AA, Golubovich VP, Ashmarin IP (1999) The effects of a novel analog of the C-terminal fragment of vasopressin on the behavior of white rats. Neurosci Behav Physiol 29(4):365–369. https://doi.org/10.1007/BF02461070 (PMID: 10582216)
Quintana A, Erta M, Ferrer B, Comes G, Giralt M, Hidalgo J (2013) Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav Immun 27:162–173. https://doi.org/10.1016/j.bbi.2012.10.011 (PMID: 23085146)
Ray J, Hansen S (2004) Temperament in the rat: sex differences and hormonal influences on harm avoidance and novelty seeking. Behav Neurosci 118(3):488–497. https://doi.org/10.1037/0735-7044.118.3.488 (PMID: 15174926)
Reinstein DK, Hannigan JH Jr, Isaacson RL (1982) Time course of certain behavioral changes after hippocampal damage and their alteration by dopaminergic intervention into nucleus accumbens. Pharmacol Biochem Behav 17(2):193–202. https://doi.org/10.1016/0091-3057(82)90069-7 (PMID: 7134232)
Renner MJ (1990) Neglected aspects of exploratory and investigatory behavior. Psychobiology 18(1):16–22
Rex A, Kolbasenko A, Bert B, Fink H (2007) Choosing the right wild type: behavioral and neurochemical differences between 2 populations of Sprague-Dawley rats from the same source but maintained at different sites. J Am Assoc Lab Anim Sci 46(5):13–20 (PMID: 17877322)
Roedel A, Storch C, Holsboer F, Ohl F (2006) Effects of light or dark phase testing on behavioural and cognitive performance in DBA mice. Lab Anim 40(4):371–381. https://doi.org/10.1258/002367706778476343 (PMID: 17018208)
Rueda N, Flórez J, Martínez-Cué C (2008) Effects of chronic administration of SGS-111 during adulthood and during the pre- and post-natal periods on the cognitive deficits of Ts65Dn mice, a model of Down syndrome. Behav Brain Res 188(2):355–367. https://doi.org/10.1016/j.bbr.2007.11.020 (PMID: 18178265)
Saiyudthong S, Marsden CA (2011) Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats. Phytother Res 25(6):858–862. https://doi.org/10.1002/ptr.3325 (PMID: 21105176)
Sampedro-Piquero P, Moreno-Fernández RD, Mañas-Padilla MC, Gil-Rodríguez S, Gavito AL, Pavón FJ, Pedraza C, García-Fernández M, Ladrón de Guevara-Miranda D, Santín LJ, Castilla-Ortega E (2018) Training memory without aversion: appetitive hole-board spatial learning increases adult hippocampal neurogenesis. Neurobiol Learn Mem 151:35–42. https://doi.org/10.1016/j.nlm.2018.03.023 (PMID: 29608953)
Sampedro-Piquero P, Mañas-Padilla MC, Ávila-Gámiz F, Gil-Rodríguez S, Santín LJ, Castilla-Ortega E (2019) Where to place the rewards? Exploration bias in mice influences performance in the classic hole-board spatial memory test. Anim Cogn 22(3):433–443. https://doi.org/10.1007/s10071-019-01256-3 (PMID: 30852738)
Sara SJ, Dyon-Laurent C, Hervé A (1995) Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system. Cogn Brain Res 2(3):181–187. https://doi.org/10.1016/0926-6410(95)90007-1 (PMID: 7580400)
Schacter GB, Yang CR, Innis NK, Mogenson GJ (1989) The role of the hippocampal-nucleus accumbens pathway in radial-arm maze performance. Brain Res 494(2):339–349. https://doi.org/10.1016/0006-8993(89)90602-1 (PMID: 2776019)
Schmid S, Rammes G, Blobner M, Kellermann K, Bratke S, Fendl D, Kaichuan Z, Schneider G, Jungwirth B (2019) Cognitive decline in Tg2576 mice shows sex-specific differences and correlates with cerebral amyloid-beta. Behav Brain Res 359:408–417. https://doi.org/10.1016/j.bbr.2018.11.022 (PMID: 30458163)
Schmidt S, Gawlik V, Hölter SM, Augustin R, Scheepers A, Behrens M, Wurst W, Gailus-Durner V, Fuchs H, Hrabé de Angelis M, Kluge R, Joost HG, Schürmann A (2008) Deletion of glucose transporter GLUT8 in mice increases locomotor activity. Behav Genet 38(4):396–406. https://doi.org/10.1007/s10519-008-9208-1 (PMID: 18461434)
Schwabe L, Schächinger H, de Kloet ER, Oitzl MS (2010) Corticosteroids operate as a switch between memory systems. J Cogn Neurosci 22(7):1362–1372. https://doi.org/10.1162/jocn.2009.21278 (PMID: 19445601)
Shi J, Cai Y, Liu G, Gong N, Liu Z, Xu T, Wang Z, Fei J (2012) Enhanced learning and memory in GAT1 heterozygous mice. Acta Biochim Biophys Sin (shanghai) 44(4):359–366. https://doi.org/10.1093/abbs/gms005 (PMID: 22318715)
Shipman ML, Green JT (2019) Cerebellum and cognition: does the rodent cerebellum participate in cognitive functions? Neurobiol Learn Mem 170:106996. https://doi.org/10.1016/j.nlm.2019.02.006 (PMID: 30771461)
Soler-Llavina GJ, Fuccillo MV, Ko J, Südhof TC, Malenka RC (2011) The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo. Proc Natl Acad Sci USA 108(40):16502–16509. https://doi.org/10.1073/pnas.1114028108 (PMID: 21953696)
Stankevicius D, Rodrigues-Costa EC, Camilo Flório J, Palermo-Neto J (2008) Neuroendocrine, behavioral and macrophage activity changes induced by picrotoxin effects in mice. Neuropharmacology 54(2):300–308. https://doi.org/10.1016/j.neuropharm.2007.09.011 (PMID: 18022650)
Takashima N, Odaka YS, Sakoori K, Akagi T, Hashikawa T, Morimura N, Yamada K, Aruga J (2011) Impaired cognitive function and altered hippocampal synapse morphology in mice lacking Lrrtm1, a gene associated with schizophrenia. PLoS ONE 6(7):e22716. https://doi.org/10.1371/journal.pone.0022716 (PMID: 21818371)
Takeda H, Tsuji M, Matsumiya T (1998) Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 350(1):21–29. https://doi.org/10.1016/s0014-2999(98)00223-4 (PMID: 9683010)
Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10):a016295. https://doi.org/10.1101/cshperspect.a016295 (PMID: 25190079)
Thifault S, Krémarik P, Lalonde R (1998) Effects of bilateral electrolytic lesions of the medial nucleus accumbens on exploration and spatial learning. Arch Physiol Biochem 106(4):297–307. https://doi.org/10.1076/apab.106.4.297.4374 (PMID: 10417856)
Thifault S, Lalonde R, Sanon N, Hamet P (2002) Comparisons between C57BL/6J and A/J mice in motor activity and coordination, hole-poking, and spatial learning. Brain Res Bull 58(2):213–218. https://doi.org/10.1016/s0361-9230(02)00782-7 (PMID: 12127020)
Thoeringer CK, Erhardt A, Sillaber I, Mueller MB, Ohl F, Holsboer F, Keck ME (2010) Long-term anxiolytic and antidepressant-like behavioural effects of tiagabine, a selective GABA transporter-1 (GAT-1) inhibitor, coincide with a decrease in HPA system activity in C57BL/6 mice. J Psychopharmacol 24(5):733–743. https://doi.org/10.1177/0269881109103091 (PMID: 19346277)
Thompson R (1981) Rapid forgetting of a spatial habit in rats with hippocampal lesions. Science 212(4497):959–960. https://doi.org/10.1126/science.6785882 (PMID: 6785882)
Thullier F, Lalonde R, Mahler P, Joyal CC, Lestienne F (1996) Dorsal striatal lesions in rats. 1: Effects on exploration and motor coordination. Arch Physiol Biochem 104(3):300–306. https://doi.org/10.1076/apab.104.3.300.12902 (PMID: 8793021)
Tohda C, Nakanishi R, Kadowaki M (2009) Hyperactivity, memory deficit and anxiety-related behaviors in mice lacking the p85alpha subunit of phosphoinositide-3 kinase. Brain Dev 31(1):69–74. https://doi.org/10.1016/j.braindev.2008.04.006 (PMID: 18538520)
Trofimova I, Robbins TW (2016) Temperament and arousal systems: a new synthesis of differential psychology and functional neurochemistry. Neurosci Biobehav Rev 64:382–402. https://doi.org/10.1016/j.neubiorev.2016.03.008 (PMID: 26969100)
van der Laan JW, Weick G, van Bleek G (1985) Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature: relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate. Biochem Pharmacol 34(21):3789–3794. https://doi.org/10.1016/0006-2952(85)90426-5 (PMID: 3933514)
van Gaalen MM, Steckler T (2000) Behavioural analysis of four mouse strains in an anxiety test battery. Behav Brain Res 115(1):95–106. https://doi.org/10.1016/s0166-4328(00)00240-0 (PMID: 10996412)
van Gaalen MM, Stenzel-Poore MP, Holsboer F, Steckler T (2002) Effects of transgenic overproduction of CRH on anxiety-like behaviour. Eur J Neurosci 15(12):2007–2015. https://doi.org/10.1046/j.1460-9568.2002.02040.x (PMID: 12099906)
Vawter MP, De Wied D, Van Ree JM (1997) Vasopressin fragment, AVP-(4–8): improves long-term and short-term memory in the hole board search task. Neuropeptides 31(5):489–494. https://doi.org/10.1016/s0143-4179(97)90044-5 (PMID: 9413027)
Watson PJ (1978) Nonmotor functions of the cerebellum. Psychol Bull 85(5):944–967 (PMID: 704722)
Whishaw IQ, Tomie J (1997) Perseveration on place reversals in spatial swimming pool tasks: further evidence for place learning in hippocampal rats. Hippocampus 7(4):361–370. https://doi.org/10.1002/(SICI)1098-1063(1997)7:4%3c361::AID-HIPO2%3e3.0.CO;2-M (PMID: 9287076)
Wu L, Feng X, Li T, Sun B, Khan MZ, He L (2017) Risperidone ameliorated Aβ1-42-induced cognitive and hippocampal synaptic impairments in mice. Behav Brain Res 322(Pt A):145–156. https://doi.org/10.1016/j.bbr.2017.01.020 (PMID: 28093254)
Yamada M, Tsukagoshi M, Hashimoto T, Oka J, Saitoh A, Yamada M (2015) Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice. J Neural Transm (vienna) 122(3):487–494. https://doi.org/10.1007/s00702-014-1289-9 (PMID: 25119538)
Zhang WN, Pothuizen HH, Feldon J, Rawlins JN (2004) Dissociation of function within the hippocampus: effects of dorsal, ventral and complete excitotoxic hippocampal lesions on spatial navigation. Neuroscience 127(2):289–300. https://doi.org/10.1016/j.neuroscience.2004.05.007 (PMID: 15262320)
Zhu SW, Codita A, Bogdanovic N, Hjerling-Leffler J, Ernfors P, Winblad B, Dickins DW, Mohammed AH (2009) Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice. Behav Brain Res 197(2):339–346. https://doi.org/10.1016/j.bbr.2008.09.032 (PMID: 18951926)
Funding
Funding was provided by laboratory resources of EA7300.
Author information
Authors and Affiliations
Contributions
Robert Lalonde conceived and wrote the paper, Catherine Strazielle reviewed and edited the paper.
Corresponding author
Ethics declarations
Conflict of interest
Robert Lalonde and Catherine Strazielle declare that they have no conflict of interest.
Ethical Approval
Not applicable.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Additional information
Edited by: Jerry Stitzel.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Lalonde, R., Strazielle, C. The Hole-Board Test in Mutant Mice. Behav Genet 52, 158–169 (2022). https://doi.org/10.1007/s10519-022-10102-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10519-022-10102-1