Ontogeny of eyeblink conditioning using a visual conditional stimulus

Paczkowski, Christine M.; Ivkovich, Dragana; Stanton, Mark E.

doi:10.1002/(sici)1098-2302(199912)35:4<253::aid-dev1>3.0.co;2-0

Cited by 23 publications

(32 citation statements)

References 22 publications

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“…Each chamber was fitted with a ventilation fan producing low frequency background noise, a house light (15W), and a speaker which delivered the auditory CS. The auditory CS was a 70 dB, 2.8 kHz tone presented for 380 milliseconds (ms) and the visual CS was activation of the house light (against the dark background) for 380 ms [5,32]. The US was a 2-mA, 100 ms, periocular shock produced by a constant-current, 60-Hz square wave stimulator (World Precision Instruments, Sarasota, FL).…”

Section: Apparatussupporting

confidence: 84%

“…On PND26 subjects began training in a tone-light discrimination as described in detail elsewhere [5,32). Each session consisted of 50 trials of a 380 ms 15-W light CS, and 50 trials of a 380 ms 70db tone CS, one of which (CS+) preceded and coterminated with a 2-mA, 100 ms periocular-shock US (delay interval = 280 ms) and the other of which (CS−) was presented alone without the shock US.…”

Section: Design and Proceduresmentioning

confidence: 99%

“…The present study used a tone-light EBC discrimination/reversal task in weanling-juvenile rats [5,32]. Weanling-juvenile rats were chosen as subjects on the basis of evidence that eyeblink conditioning effects in autism are larger in children than in adults [40].…”

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confidence: 99%

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Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism

Stanton

Peloso

Brown

et al. 2007

Behavioural Brain Research

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Offspring of rats exposed to valproic acid (VPA) on Gestational Day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases [20,37]. Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning [40] and in reversal of instrumental discrimination learning [9]. Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 [cf. 37] and tested their offspring from PND26-31 on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children [40]. This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry [37] are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder. KeywordsEyeblink Conditioning; Gestational Valproate Exposure; Discrimination Reversal; Cerebellum; Hippocampus; Development The purpose of this article is to use a developmental rodent model of eyeblink conditioning to gather evidence bearing on the hypothesis that early gestational injury to the brainstem plays a role in the etiology of autism [3,37,39]. Evidence for this hypothesis arises from a disparate set of findings that show remarkable convergence [39]. The first clues came from reports of an association between autism and early gestational exposure to thalidomide and misoprostol [27]. Knowledge concerning the teratology of thalidomide permits inferences concerning the timing of thalidomide exposure based on the presence of craniofacial defects (ear anomolies). When thalidomide cases involving exposure specifically between 20-24 days post-conception were considered, autism occurred at a staggering rate (~30%, [39]). It was subsequently

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Section: Apparatussupporting

confidence: 84%

Section: Design and Proceduresmentioning

confidence: 99%

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Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism

Stanton

Peloso

Brown

et al. 2007

Behavioural Brain Research

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“…Eyeblink conditioning has been attained by using auditory, somatosensory, or visual CSs paired with an air-puff to the eye or a strong periorbital shock as USs (Gormezano et al 1983;Paczkowski et al 1999;Gruart et al 2000). Das and colleagues (2001) obtained eyeblink conditioning in rabbits by using vibratory stimulation of the mystacial vibrissae as CS.…”

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confidence: 94%

Classical conditioning of eyelid and mystacial vibrissae responses in conscious mice

Troncoso

Múnera²,

Delgado‐García³

2004

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The murine vibrissae sensorimotor system has been scrutinized as a target of motor learning through trace classical conditioning. Conditioned eyelid responses were acquired by using weak electrical whisker-pad stimulation as conditioned stimulus (CS) and strong electrical periorbital stimulation as unconditioned stimulus (US). In addition, conditioned vibrissal protraction was obtained pairing either weak electrical whisker-pad stimulation or a tone as CS, with a strong electric shock delivered in the whisker-pad as US. 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.Classical conditioning of blink responses is widely used to explore the neural mechanisms underlying associative learning and memory storage in diverse species (Gormezano et al. 1983;Gruart et al. 1995;Bao et al. 1998;Weiss et al. 1999;Zhao et al. 1999). This conditioning is acquired after repetitive and contingent paired presentations of a neutral, conditioned stimulus (CS) and a blink-evoking, unconditioned stimulus (US).Eyeblink conditioning has been attained by using auditory, somatosensory, or visual CSs paired with an air-puff to the eye or a strong periorbital shock as USs (Gormezano et al. 1983;Paczkowski et al. 1999;Gruart et al. 2000). Das and colleagues (2001) obtained eyeblink conditioning in rabbits by using vibratory stimulation of the mystacial vibrissae as CS.The vibrissal sensorimotor system is used to scan object surfaces, extracting detailed information from the environment (Woolsey and Van der Loos 1970;Carvell et al. 1991). Both behavioral (Bermejo et al. 1996) and experience-induced cortical plasticity (Fox 2002) have been demonstrated as a result of adult whisker manipulations. Here, we examined the possibility of using stimulation of its sensory branch as CS and/or its motor branch as the generator of conditioned responses (CRs). Thus, we evaluated the acquisition of eyeblink conditioning by using electrical stimulation of the mystacial vibrissae as CS, and the acquisition of conditioned vibrissal protraction by using either electrical stimulation of the mystacial vibrissae or auditory stimulation, also as CS. Whisker-pad electrical stimulation as CS during blink conditioningAn isolated weak electrical stimulus in the whisker-pad occasionally elicited a variable-latency (∼25 to 35 msec), brief (<10 msec), low-voltage (<20 µV) blink response (Fig. 1C). When this CS was consistently paired with a strong electric shock in periorbital region (US), using a trace paradigm (w-E), the subjects gradually displayed CRs (%CR: F (9,90) = 57.321, P < 0.001; amplitude: F (9,90) = 19.635, P < 0.001) (Fig. 1A,B). Initially, these responses were brief and had variable latency (Fig. 1C); however, as the training advanced, the CRs acquired long latency and an in crescendo profile (Fig. 1C). During extinction, CR frequency progressively decreased (F (3,36) = 25.901...

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“…Eyeblink conditioning increases substantially between P17 and P24 when standard peripheral stimuli (e.g., tones, lights) are used as CSs (Stanton et al 1992(Stanton et al , 1998Paczkowski et al 1999). Development of sensory inputs to the pontine nuclei is a rate-limiting factor in the ontogeny of eyeblink conditioning using auditory CSs Ng and Freeman 2012), and bypassing these inputs by using electrical stimulation of the pontine nuclei as a CS overcomes developmental limitations observed with auditory (and visual) CSs (Freeman et al 2005).…”

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confidence: 99%

Extinction, reacquisition, and rapid forgetting of eyeblink conditioning in developing rats

Brown

Freeman

2014

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Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In Experiment 1, post-natal day (P) 17 and 24 rats were trained to a criterion of 80% conditioned responses (CRs) using stimulation of the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS). Stimulation CS-alone extinction training commenced 24 h later, followed by reacquisition training after the fourth extinction session. Contrary to expected results, rats trained starting on P17 showed significantly fewer CRs to stimulation CS-alone presentations relative to P24s, including fewer CRs as early as the first block of extinction session 1. Furthermore, the P17 group was slower to reacquire following extinction. Experiment 2 was run to determine the extent to which the low CR percentage observed in P17s early in extinction reflected rapid forgetting versus rapid extinction. Twenty-four hours after reaching criterion, subjects were trained in a session split into 50 stimulation CS-unconditioned stimulus paired trials followed immediately by 50 stimulation CS-alone trials. With this "immediate" extinction protocol, CR percentages during the first block of stimulation CSalone presentations were equivalent to terminal acquisition levels at both ages but extinction was more rapid in the P17 group. These findings indicate that forgetting is observed in P17 relative to P24 rats 24 h following acquisition. The forgetting in P17 rats has important implications for the neurobiological mechanisms of memory in the developing cerebellum.

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Ontogeny of eyeblink conditioning using a visual conditional stimulus

Cited by 23 publications

References 22 publications

Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism

Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism

Classical conditioning of eyelid and mystacial vibrissae responses in conscious mice

Extinction, reacquisition, and rapid forgetting of eyeblink conditioning in developing rats

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