Genomes and Genes
Summary: Reflex closure of the eyelid occurring as a result of classical conditioning.
- Delgado Garcia J, Gruart A. Building new motor responses: eyelid conditioning revisited. Trends Neurosci. 2006;29:330-8 pubmed..This review is part of the TINS special issue on The Neural Substrates of Cognition. ..
- Attwell P, Ivarsson M, Millar L, Yeo C. Cerebellar mechanisms in eyeblink conditioning. Ann N Y Acad Sci. 2002;978:79-92 pubmed..Our findings indicate that a fully functional olivo-cortico-nuclear loop is required to express all characteristics of associatively conditioned responses. ..
- Lepora N, Mavritsaki E, Porrill J, Yeo C, Evinger C, Dean P. Evidence from retractor bulbi EMG for linearized motor control of conditioned nictitating membrane responses. J Neurophysiol. 2007;98:2074-88 pubmed..Analysis of a detailed plant model suggests that one method for linearising the plant would be appropriate recruitment of motor units...
- Kreider J, Mauk M. Eyelid conditioning to a target amplitude: adding how much to whether and when. J Neurosci. 2010;30:14145-52 pubmed publisherConceptual and practical advantages of pavlovian eyelid conditioning facilitate analysis of cerebellar computation and learning. Even so, eyelid conditioning procedures are unrealistic in an important way...
- Kishimoto Y, Fujimichi R, Araishi K, Kawahara S, Kano M, Aiba A, et al. mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning. Eur J Neurosci. 2002;16:2416-24 pubmed..In contrast, mGluR1 in other cell types is required for associating discontiguous stimuli and long-term memory formation in nonspatial hippocampus-dependent learning. ..
- Svensson P, Bengtsson F, Hesslow G. Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret. Exp Brain Res. 2006;168:241-53 pubmed..The duration of the strongest inhibition was short and had a sharp peak at about 30 ms. It is suggested that the time course of the inhibition is important for temporal regulation of learned responses...
- Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb F, Frings M, et al. Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci. 2005;25:3919-31 pubmed..Extracerebellar premotoneuronal disinhibition, however, is another possible explanation for changes in CR timing...
- Bracha V, Zhao L, Irwin K, Bloedel J. The human cerebellum and associative learning: dissociation between the acquisition, retention and extinction of conditioned eyeblinks. Brain Res. 2000;860:87-94 pubmed..This finding suggests that in humans, the acquisition of new and the extinction of previously learned conditioned responses depends on a similar set of cerebellar circuits. ..
- Ohyama T, Mauk M. Latent acquisition of timed responses in cerebellar cortex. J Neurosci. 2001;21:682-90 pubmedEvidence indicates that rabbit eyelid conditioning is mediated by plasticity in the interpositus cerebellar nucleus and in cerebellar cortex...
- Pugh J, Raman I. Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current. Neuron. 2006;51:113-23 pubmed..Based on predictions of neuronal activity during delay eyelid conditioning, we developed quasi-physiological induction protocols consisting of high-frequency mossy fiber stimulation ..
- López Ramos J, Yi P, Eleore L, Madroñal N, Rueda A, Delgado Garcia J. Classical eyeblink conditioning during acute hypobaric hypoxia is improved in acclimatized mice and involves Fos expression in selected brain areas. J Appl Physiol (1985). 2007;103:1479-87 pubmed
- Eleore L, López Ramos J, Yi P, Delgado Garcia J. The cognitive enhancer T-588 partially compensates the motor associative learning impairments induced by scopolamine injection in mice. Behav Neurosci. 2007;121:1203-14 pubmed..These results suggest that T-588 could be used as a pharmacological agent to improve motor and associative learning disorders. ..
- Robleto K, Thompson R. Extinction of a classically conditioned response: red nucleus and interpositus. J Neurosci. 2008;28:2651-8 pubmed publisher..These findings speak to the important role of cerebellar structures in the extinction of discrete motor responses and provide important insight as to the validity of a particular theory of extinction. ..
- Koekkoek S, Hulscher H, Dortland B, Hensbroek R, Elgersma Y, Ruigrok T, et al. Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science. 2003;301:1736-9 pubmed..Here, we show that protein kinase C-dependent long-term depression in Purkinje cells is necessary for learning-dependent timing of Pavlovian-conditioned eyeblink responses. ..
- Sánchez Campusano R, Gruart A, Delgado Garcia J. Dynamic associations in the cerebellar-motoneuron network during motor learning. J Neurosci. 2009;29:10750-63 pubmed publisher..Thus, it can be proposed that the cerebellum is always looking back and reevaluating its own function, using the information acquired in the process, to play a modulating-reinforcing role in motor learning. ..
- Kalmbach B, Ohyama T, Kreider J, Riusech F, Mauk M. Interactions between prefrontal cortex and cerebellum revealed by trace eyelid conditioning. Learn Mem. 2009;16:86-95 pubmed publisherb>Eyelid conditioning has proven useful for analysis of learning and computation in the cerebellum. Two variants, delay and trace conditioning, differ only by the relative timing of the training stimuli...
- De Zeeuw C, Yeo C. Time and tide in cerebellar memory formation. Curr Opin Neurobiol. 2005;15:667-74 pubmed
- Huber K. The fragile X-cerebellum connection. Trends Neurosci. 2006;29:183-5 pubmed..This work forges an important link between the FMR1 gene, altered synaptic plasticity in the cerebellum and mental retardation. ..
- Bangasser D, Shors T. Acute stress impairs trace eye blink conditioning in females without altering the unconditioned response. Neurobiol Learn Mem. 2004;82:57-60 pubmed..Taken together, these experiments indicate that the stress-induced impairment of conditioning in females is not due to a decreased perception of US strength. ..
- Choi J, Moore J. Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses. Behav Neurosci. 2003;117:1211-9 pubmed..The striking similarity between the time course of bimodal CRs and neuronal responses indicates that neuronal activities in the cerebellum are causally related to the production of behavioral CRs. ..
- Freeman J, Muckler A. Developmental changes in eyeblink conditioning and neuronal activity in the pontine nuclei. Learn Mem. 2003;10:337-45 pubmed..The developmental changes in pontine neuronal activity might play a significant role in the ontogeny of eyeblink conditioning. ..
- Delgado Garcia J, Gruart A. Firing activities of identified posterior interpositus nucleus neurons during associative learning in behaving cats. Brain Res Brain Res Rev. 2005;49:367-76 pubmed..Moreover, interpositus neurons probably contribute to the proper damping of newly acquired eyelid responses. The contributing role of other neuronal centers and circuits related to the eyelid motor system are also discussed. ..
- Kalmbach B, Ohyama T, Mauk M. Temporal patterns of inputs to cerebellum necessary and sufficient for trace eyelid conditioning. J Neurophysiol. 2010;104:627-40 pubmed publisherTrace eyelid conditioning is a form of associative learning that requires several forebrain structures and cerebellum...
- 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;88:2124-33 pubmed..These data show that MDMT can be used to measure the kinetics and frequency domain properties of conditioned eyelid responses in mice and that these properties follow the dynamic characteristics of other mammals. ..
- Bolbecker A, Mehta C, Edwards C, Steinmetz J, O Donnell B, Hetrick W. Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia. Schizophr Res. 2009;111:182-91 pubmed publisher..These findings are consistent with models of schizophrenia in which disruptions within the cortico-cerebellar-thalamic-cortical (CCTC) brain circuit are postulated to underlie the cognitive fragmentation that characterizes the disorder. ..
- Brown K, Calizo L, Stanton M. Dose-dependent deficits in dual interstimulus interval classical eyeblink conditioning tasks following neonatal binge alcohol exposure in rats. Alcohol Clin Exp Res. 2008;32:277-93 pubmed..Applications of this EBC task to humans may enable reliable early identification and diagnosis of individuals with fetal alcohol spectrum disorders. ..
- Wikgren J, Nokia M, Penttonen M. Hippocampo-cerebellar theta band phase synchrony in rabbits. Neuroscience. 2010;165:1538-45 pubmed publisher..Future studies should examine cerebellar unit activity in relation to hippocampal theta oscillations in order to discover the detailed mechanisms of theta-paced neural activity. ..
- Weible A, Weiss C, Disterhoft J. Activity profiles of single neurons in caudal anterior cingulate cortex during trace eyeblink conditioning in the rabbit. J Neurophysiol. 2003;90:599-612 pubmed..Taken together, these data suggest that the caudal AC is involved early in trace eyeblink conditioning and that maintenance of the CS-elicited excitatory response may serve to signal the salience of the tone. ..
- Troncoso J, Múnera A, Delgado García J. Classical conditioning of eyelid and mystacial vibrissae responses in conscious mice. Learn Mem. 2004;11:724-6 pubmed..This finding suggests that evolutionary pressure has selected a sensorimotor system capable of constructing conditioned responses on the basis of temporal relationships of stimuli, independently of any putative functional purpose. ..
- Zbarska S, Bloedel J, Bracha V. Cerebellar dysfunction explains the extinction-like abolition of conditioned eyeblinks after NBQX injections in the inferior olive. J Neurosci. 2008;28:10-20 pubmed publisher..These findings indicate that testing the role of IO in learning requires methods that do not alter the functional state of the cerebellum. ..
- Halverson H, Freeman J. Medial auditory thalamic input to the lateral pontine nuclei is necessary for auditory eyeblink conditioning. Neurobiol Learn Mem. 2010;93:92-8 pubmed publisher..The results provide evidence that the auditory CS pathway necessary for delay eyeblink conditioning includes the MATN-LPN projection and the visual CS pathway includes the MPN. ..
- Brown K, Stanton M. Cross-modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young rats. Dev Psychobiol. 2008;50:647-64 pubmed publisher..ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction. ..
- Steinmetz A, Edwards C, Steinmetz J, Hetrick W. Comparison of auditory and visual conditioning stimuli in delay eyeblink conditioning in healthy young adults. Learn Behav. 2009;37:349-56 pubmed publisher..In addition, CR timing improved across testing sessions, as indicated by the later CR peak latencies exhibited during the second testing session, as compared with the first. ..
- Allen M, Padilla Y, Gluck M. Ibotenic acid lesions of the medial septum retard delay eyeblink conditioning in rabbits (Oryctolagus cuniculus). Behav Neurosci. 2002;116:733-8 pubmed..This finding demonstrates that the selective removal of the medial septum retards delay eyeblink conditioning in a manner similar to the disruption seen after systemic administration of scopolamine. ..
- Gerwig M, Hajjar K, Frings M, Dimitrova A, Thilmann A, Kolb F, et al. Extinction of conditioned eyeblink responses in patients with cerebellar disorders. Neurosci Lett. 2006;406:87-91 pubmed..It cannot be ruled out, however, that impaired acquisition affected the extinction results. ..
- Hollander H, Bender S. ECEM (eye closure eye movements): integrating aspects of EMDR with hypnosis for treatment of trauma. Am J Clin Hypn. 2001;43:187-202 pubmed..In ECEM the eye movement variable of EMDR is integrated within a hypnosis protocol to enhance benefits of hypnosis and reduce certain risks of EMDR. ..
- Kato Y, Takatsuki K, Kawahara S, Fukunaga S, Mori H, Mishina M, et al. N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit delta2 mutant mice. Neuroscience. 2005;135:1017-23 pubmed..These results suggest that N-methyl-D-aspartate receptors play critical roles both in acquisition and expression of the conditioned response in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice. ..
- Lee T, Kim J, Wagner A. Discriminative conditioning with different CS-US intervals produces temporally differentiated conditioned responses in the two eyes of the rabbit (Oryctolagus cuniculus). Behav Neurosci. 2009;123:1085-94 pubmed publisher..The results indicate that the neuronal substrates subserving CRs of the two eyes involve not only a dominant lateralization but also some avenue of bilaterality. ..
- McEchron M, Alexander D, Smith M, Hoffman D, Podskalny G, Connor J. Altered eyeblink reflex conditioning in restless legs syndrome patients. Sleep Med. 2010;11:314-9 pubmed publisher..Together these results suggest that deficits in eyeblink conditioning are related to the pathophysiology of RLS. The eyeblink conditioning test may also be useful for supporting a clinical diagnosis or treatment strategy for RLS. ..
- Mauk M, Ohyama T. Extinction as new learning versus unlearning: considerations from a computer simulation of the cerebellum. Learn Mem. 2004;11:566-71 pubmedLike many forms of Pavlovian conditioning, eyelid conditioning displays robust extinction...
- Kronenbuerger M, Tronnier V, Gerwig M, Fromm C, Coenen V, Reinacher P, et al. Thalamic deep brain stimulation improves eyeblink conditioning deficits in essential tremor. Exp Neurol. 2008;211:387-96 pubmed publisher..Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role. ..
- Leuner B, Waddell J, Gould E, Shors T. Temporal discontiguity is neither necessary nor sufficient for learning-induced effects on adult neurogenesis. J Neurosci. 2006;26:13437-42 pubmed..Together, these results demonstrate that associative learning increases the survival of new neurons in the adult hippocampus, regardless of temporal contiguity. ..
- Stanton M, Peloso E, Brown K, Rodier P. Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism. Behav Brain Res. 2007;176:133-40 pubmed..Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder. ..
- Simon B, Knuckley B, Churchwell J, Powell D. Post-training lesions of the medial prefrontal cortex interfere with subsequent performance of trace eyeblink conditioning. J Neurosci. 2005;25:10740-6 pubmed
- Miller M, Weiss C, Song X, Iordanescu G, Disterhoft J, Wyrwicz A. Functional magnetic resonance imaging of delay and trace eyeblink conditioning in the primary visual cortex of the rabbit. J Neurosci. 2008;28:4974-81 pubmed publisher..To our knowledge, this work is the first functional imaging study to compare directly trace and delay eyeblink conditioning in an animal model. ..
- Freeman J, Campolattaro M. Ontogenetic change in the auditory conditioned stimulus pathway for eyeblink conditioning. Learn Mem. 2008;15:823-8 pubmed publisher..The findings suggest that the thalamic contribution to auditory eyeblink conditioning continues to develop through the first postnatal month. ..
- Das S, Weiss C, Disterhoft J. Eyeblink conditioning in the rabbit (Oryctolagus cuniculus) with stimulation of the mystacial vibrissae as a conditioned stimulus. Behav Neurosci. 2001;115:731-6 pubmed..Vibrotactile stimulation of the vibrissae as a CS will enable further examination of the neural correlates of learning in a well-characterized sensory system. ..
- McLaughlin J, Flaten M, Chachich M, Powell D. Medial prefrontal lesions attenuate conditioned reflex facilitation but do not affect prepulse modification of the eyeblink reflex in rabbits. Exp Brain Res. 2001;140:318-25 pubmed..Unlike conditioned facilitation, prepulse modification was unaffected by mPFC lesions. ..
- Medina J, Repa J, Mauk M, LeDoux J. Parallels between cerebellum- and amygdala-dependent conditioning. Nat Rev Neurosci. 2002;3:122-31 pubmed..So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems. ..
- Flores L, Disterhoft J. Caudate nucleus is critically involved in trace eyeblink conditioning. J Neurosci. 2009;29:14511-20 pubmed publisher..These data demonstrate that the CN is required for and involved in trace EBC. ..
- Wikgren J, Ruusuvirta T, Korhonen T. Reflex facilitation during eyeblink conditioning and subsequent interpositus nucleus inactivation in the rabbit (Oryctolagus cuniculus). Behav Neurosci. 2002;116:1052-8 pubmed..In Experiment 2, reversible inactivation of the interpositus nucleus (IPN) abolished the CR and reduced the CR-related reflex facilitation, indicating that the latter depends on the plasticity of the IPN. ..
- Hodes G, Shors T. Learning during middle age: a resistance to stress?. Neurobiol Aging. 2007;28:1783-8 pubmed..Together, these data indicate that associative learning in the aging animal is resistant to both the negative and positive consequences of stressful experience. ..