Cerebellar and Extracerebellar Involvement in Mouse Eyeblink Conditioning: the ACDC Model

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2010 Feb 4

PMID 20126519

Citations 61

Authors

Henk-Jan Boele

Sebastiaan K E Koekkoek

Chris I De Zeeuw

Affiliations

Soon will be listed here.

Abstract

Over the past decade the advent of mouse transgenics has generated new perspectives on the study of cerebellar molecular mechanisms that are essential for eyeblink conditioning. However, it also appears that results from eyeblink conditioning experiments done in mice differ in some aspects from results previously obtained in other mammals. In this review article we will, based on studies using (cell-specific) mouse mutants and region-specific lesions, re-examine the general eyeblink behavior in mice and the neuro-anatomical circuits that might contribute to the different peaks in the conditioned eyeblink trace. We conclude that the learning process in mice has at least two stages: An early stage, which includes short-latency responses that are at least partly controlled by extracerebellar structures such as the amygdala, and a later stage, which is represented by well-timed conditioned responses that are mainly controlled by the pontocerebellar and olivocerebellar systems. We refer to this overall concept as the Amygdala-Cerebellum-Dynamic-Conditioning Model (ACDC model).

Citing Articles

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References

Pilz P, Caeser M, Ostwald J . Comparative threshold studies of the acoustic pinna, jaw and startle reflex in the rat. Physiol Behav. 1988; 43(4):411-5. DOI: 10.1016/0031-9384(88)90112-6. View

Smith D, Gallagher M, Stanton M . Genetic background differences and nonassociative effects in mouse trace fear conditioning. Learn Mem. 2007; 14(9):597-605. PMC: 1994077. DOI: 10.1101/lm.614807. View

Qiao X, Chen L, Gao H, Bao S, Hefti F, Thompson R . Cerebellar brain-derived neurotrophic factor-TrkB defect associated with impairment of eyeblink conditioning in Stargazer mutant mice. J Neurosci. 1998; 18(17):6990-9. PMC: 6792950. View

Yeo C, Hardiman M, Glickstein M . Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI. Exp Brain Res. 1985; 60(1):114-26. DOI: 10.1007/BF00237024. View

Sacchetti B, Scelfo B, Strata P . The cerebellum: synaptic changes and fear conditioning. Neuroscientist. 2005; 11(3):217-27. DOI: 10.1177/1073858405276428. View

Killcross S, Robbins T, Everitt B . Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala. Nature. 1997; 388(6640):377-80. DOI: 10.1038/41097. View

Supple Jr W, LEATON R . Lesions of the cerebellar vermis and cerebellar hemispheres: effects on heart rate conditioning in rats. Behav Neurosci. 1990; 104(6):934-47. DOI: 10.1037//0735-7044.104.6.934. View

GORMEZANO I, Schneiderman N, DEAUX E, Fuentes I . Nictitating membrane: classical conditioning and extinction in the albino rabbit. Science. 1962; 138(3536):33-4. DOI: 10.1126/science.138.3536.33. View

Freeman Jr J, Rabinak C . Eyeblink conditioning in rats using pontine stimulation as a conditioned stimulus. Integr Physiol Behav Sci. 2005; 39(3):180-91. PMC: 1249521. DOI: 10.1007/BF02734438. View

10.

Gould T, Sears L, Steinmetz J . Possible CS and US pathways for rabbit classical eyelid conditioning: electrophysiological evidence for projections from the pontine nuclei and inferior olive to cerebellar cortex and nuclei. Behav Neural Biol. 1993; 60(2):172-85. DOI: 10.1016/0163-1047(93)90285-p. View

11.

Koekkoek S, Yamaguchi K, Milojkovic B, Dortland B, Ruigrok T, Maex R . Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron. 2005; 47(3):339-52. DOI: 10.1016/j.neuron.2005.07.005. View

12.

Pare D, Quirk G, LeDoux J . New vistas on amygdala networks in conditioned fear. J Neurophysiol. 2004; 92(1):1-9. DOI: 10.1152/jn.00153.2004. View

13.

Lee T, Kim J . Differential effects of cerebellar, amygdalar, and hippocampal lesions on classical eyeblink conditioning in rats. J Neurosci. 2004; 24(13):3242-50. PMC: 6730028. DOI: 10.1523/JNEUROSCI.5382-03.2004. View

14.

Morcuende S, Delgado-Garcia J, Ugolini G . Neuronal premotor networks involved in eyelid responses: retrograde transneuronal tracing with rabies virus from the orbicularis oculi muscle in the rat. J Neurosci. 2002; 22(20):8808-18. PMC: 6757699. View

15.

Koekkoek S, Den Ouden W, Perry G, Highstein S, de Zeeuw C . Monitoring kinetic and frequency-domain properties of eyelid responses in mice with magnetic distance measurement technique. J Neurophysiol. 2002; 88(4):2124-33. DOI: 10.1152/jn.2002.88.4.2124. View

16.

Pellegrini J, Horn A, Evinger C . The trigeminally evoked blink reflex. I. Neuronal circuits. Exp Brain Res. 1995; 107(2):166-80. DOI: 10.1007/BF00230039. View

17.

Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M . Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar Purkinje cells. Biochem Biophys Res Commun. 1993; 197(3):1267-76. DOI: 10.1006/bbrc.1993.2614. View

18.

Oberdick J, Smeyne R, Mann J, Zackson S, Morgan J . A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science. 1990; 248(4952):223-6. DOI: 10.1126/science.2109351. View

19.

Delgado-Garcia J, Gruart A . The role of interpositus nucleus in eyelid conditioned responses. Cerebellum. 2003; 1(4):289-308. DOI: 10.1080/147342202320883597. View

20.

Woody C, Aou S . Identification of differently timed motor components of conditioned blink responses. Brain Res. 1999; 836(1-2):79-89. DOI: 10.1016/s0006-8993(99)01613-3. View