Contribution of CaMKIV to injury and fear- induced ultrasonic vocalizations in adult mice

Molecular Pain

Min Zhuo²  Talal Chatila¹  Shanelle W Ko² 

[1] Department of Pediatrics, The David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles CA 90095-1752, USA;Department of Physiology, University of Toronto, Centre for the Study of Pain, Faculty of Medicine, Medical Science Building, Room #3342, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada

关键词: mice;    CaMKIV;    pain;    memory;    fear;    Ultrasonic vocalization;   

Others  :  1180375
DOI  :  10.1186/1744-8069-1-10

 received in 2004-12-15, accepted in 2005-03-22,  发布年份 2005

【 摘 要 】

Calcium-calmodulin dependent protein kinase IV (CaMKIV) is a protein kinase that activates the transcription factor CREB. Our previous work demonstrated that mice lacking CaMKIV had a defect in fear memory while behavioral responses to noxious stimuli were unchanged. Here, we measured ultrasonic vocalizations (USVs) before and after fear conditioning and in response to a noxious injection of capsaicin to measure behavioral responses to emotional stimuli. Consistent with previous findings, behavioral nociceptive responses to capsaicin were undistinguishable between wild-type and CaMKIV^-/- mice. Wild-type animals showed a selective increase in 50 kHz USVs in response to capsaicin while such an increase was absent in CaMKIV^-/- mice. The foot shock given during fear conditioning caused an increase in 30 kHz USVs in both wild-type and CaMKIV^-/- mice. When returned to the context one hour later, USVs from the wild-type were significantly decreased. Additionally, the onset of a tone, which had previously been paired with the foot shock, caused a significant decrease in USVs during auditory conditioning. CaMKIV^-/- mice showed significantly less reduction in USVs when placed in the same context three days after receiving the shock, consistent with the decrease in freezing reported previously. Our results provide a new approach for investigating the molecular mechanism for emotional vocalization in mice and suggest that CaMKIV dependent signaling pathways play an important role in the emotional response to pain and fear.

【 授权许可】

   
2005 Ko et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ: Deficient long-term memory in mice with a targeted mutation of the cAMP- responsive element-binding protein. Cell 1994, 79:59-68.
• [2]Yin JC, Del Vecchio M, Zhou H, Tully T: CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 1995, 81:107-115.
• [3]Yin JC, Wallach JS, Del Vecchio M, Wilder EL, Zhou H, Quinn WG, Tully T: Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 1994, 79:49-58.
• [4]Kogan JH, Frankland PW, Blendy JA, Coblentz J, Marowitz Z, Schutz G, Silva AJ: Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol 1997, 7:1-11.
• [5]Guzowski JF, McGaugh JL: Antisense oligodeoxynucleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. Proc Natl Acad Sci U S A 1997, 94:2693-2698.
• [6]Cho YH, Giese KP, Tanila H, Silva AJ, Eichenbaum H: Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice. Science 1998, 279:867-869.
• [7]Lamprecht R, Dudai Y: Transient expression of c-Fos in rat amygdala during training is required for encoding conditioned taste aversion memory. Learn Mem 1996, 3:31-41.
• [8]Barrot M, Olivier JD, Perrotti LI, DiLeone RJ, Berton O, Eisch AJ, Impey S, Storm DR, Neve RL, Yin JC, Zachariou V, Nestler EJ: CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Proc Natl Acad Sci U S A 2002, 99:11435-11440.
• [9]Soderling TR: The Ca-calmodulin-dependent protein kinase cascade. Trends Biochem Sci 1999, 24:232-236.
• [10]Wei F, Qiu CS, Liauw J, Robinson DA, Ho N, Chatila T, Zhuo M: Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 2002, 5:573-579.
• [11]Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR, McKnight GS: Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol 1994, 14:6107-6116.
• [12]Jensen KF, Ohmstede CA, Fisher RS, Sahyoun N: Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex. Proc Natl Acad Sci U S A 1991, 88:2850-2853.
• [13]Nakamura Y, Okuno S, Sato F, Fujisawa H: An immunohistochemical study of Ca2+/calmodulin-dependent protein kinase IV in the rat central nervous system: light and electron microscopic observations. Neuroscience 1995, 68:181-194.
• [14]Bushnell MC, Duncan GH, Hofbauer RK, Ha B, Chen JI, Carrier B: Pain perception: is there a role for primary somatosensory cortex? Proc Natl Acad Sci U S A 1999, 96:7705-7709.
• [15]Davidson RJ, Putnam KM, Larson CL: Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence. Science 2000, 289:591-594.
• [16]LeDoux JE: Emotion circuits in the brain. Annu Rev Neurosci 2000, 23:155-184.
• [17]Davis M: The role of the amygdala in fear and anxiety. Annu Rev Neurosci 1992, 15:353-375.
• [18]Davis CM, Ambros-Ingerson J, Granger R, Wu J, Zabaneh R, Abdelnaby M, Lynch G: Triazolam impairs delayed recall but not acquisition of various everyday memory tasks in humans. Exp Neurol 1997, 148:124-134.
• [19]Ho N, Liauw JA, Blaeser F, Wei F, Hanissian S, Muglia LM, Wozniak DF, Nardi A, Arvin KL, Holtzman DM, Linden DJ, Zhuo M, Muglia LJ, Chatila TA: Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr- deficient mice. J Neurosci 2000, 20:6459-6472.
• [20]Nyby J, Whitney G, Schmitz S, Dizinno G: Postpubertal experience establishes signal value of mammaliam sex odor. Behav Biol 1978, 22:545-552.
• [21]Sales GD: Ultrasound and aggressive behaviour in rats and other small mammals. Anim Behav 1972, 20:88-100.
• [22]Sewell GD: Ultrasound in adult rodents. Nature 1967, 215:512.
• [23]Branchi I, Santucci D, Alleva E: Ultrasonic vocalisation emitted by infant rodents: a tool for assessment of neurobehavioural development. Behav Brain Res 2001, 125:49-56.
• [24]Miczek KA: Tolerance to the analgesic, but not discriminative stimulus effects of morphine after brief social defeat in rats. Psychopharmacology (Berl) 1991, 104:181-186.
• [25]Burgdorf J, Knutson B, Panksepp J, Shippenberg TS: Evaluation of rat ultrasonic vocalizations as predictors of the conditioned aversive effects of drugs. Psychopharmacology (Berl) 2001, 155:35-42.
• [26]Miczek KA, Weerts EM, Vivian JA, Barros HM: Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology (Berl) 1995, 121:38-56.
• [27]Jelen P, Soltysik S, Zagrodzka J: 22-kHz ultrasonic vocalization in rats as an index of anxiety but not fear: behavioral and pharmacological modulation of affective state. Behav Brain Res 2003, 141:63-72.
• [28]Antoniadis EA: Amygdala, hippocampus and discriminative fear conditioning to context. Behav Brain Res 2000, 108:1-19.
• [29]White NR, Prasad M, Barfield RJ, Nyby JG: 40- and 70-kHz vocalizations of mice (Mus musculus) during copulation. Physiol Behav 1998, 63:467-473.
• [30]Panksepp J, Knutson B, Burgdorf J: The role of brain emotional systems in addictions: a neuro-evolutionary perspective and new 'self-report' animal model. Addiction 2002, 97:459-469.
• [31]Cuomo V, De Salvia MA, Maselli MA, Santo L, Cagiano R: Ultrasonic calling in rodents: a new experimental approach in behavioural toxicology. Neurotoxicol Teratol 1987, 9:157-160.
• [32]Caterina MJ, Julius D: The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 2001, 24:487-517.
• [33]Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389:816-824.
• [34]Knutson B, Burgdorf J, Panksepp J: High-frequency ultrasonic vocalizations index conditioned pharmacological reward in rats. Physiol Behav 1999, 66:639-643.
• [35]Knutson B, Burgdorf J, Panksepp J: Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 2002, 128:961-977.
• [36]Wei F, Zhuo M: Potentiation of sensory responses in the anterior cingulate cortex following digit amputation in the anaesthetised rat. J Physiol 2001, 532:823-833.
• [37]Crawley JN: Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res 1999, 835:18-26.
• [38]Palecek J, Paleckova V, Willis WD: The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling nociceptive somatic and visceral stimuli in rats. Pain 2002, 96:297-307.
• [39]Burgdorf J, Knutson B, Panksepp J: Anticipation of rewarding electrical brain stimulation evokes ultrasonic vocalization in rats. Behav Neurosci 2000, 114:320-327.
• [40]Jourdan D, Ardid D, Eschalier A: Analysis of ultrasonic vocalisation does not allow chronic pain to be evaluated in rats. Pain 2002, 95:165-173.
• [41]Antoniadis EA: Fear conditioning to context expressed by multiple measures of fear in the rat. Behav Brain Res 1999, 101:1-14.
• [42]Agell N, Bachs O, Rocamora N, Villalonga P: Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. Cell Signal 2002, 14:649-654.