Brain Mechanisms of Extinction of the Classically Conditioned Eyeblink Response

Rats administered the cannabinoid agonist WIN55,212-2 or the antagonist SR141716A exhibit marked deficits during acquisition of delay eyeblink conditioning, as noted by Steinmetz and Freeman in an earlier study. However, the effects of these drugs on retention and extinction of eyeblink conditioning have not been assessed. The present study examined the effects of WIN55,212-2 and SR141716A on retention and extinction of delay eyeblink conditioning in rats. Rats were given acquisition training for five daily sessions followed by one session of retention training with subcutaneous administration of 3 mg/kg of WIN55,212-2 or 5 mg/kg of SR141716A and an additional session with the vehicle. Two sessions of extinction training were then given with WIN55,212-2, SR141716A, or vehicle. Retention and extinction were impaired by WIN55,212-2, whereas SR141716A produced no deficits. The extinction deficit in rats given WIN55,212-2 was observed only during the first session, suggesting a specific impairment in short-term plasticity mechanisms. The current results and previous findings indicate that the cannabinoid system modulates cerebellar contributions to acquisition, retention, and extinction of eyeblink conditioning.

Section: Discussionmentioning

confidence: 99%

Retention and extinction of delay eyeblink conditioning are modulated by central cannabinoids

Steinmetz¹,

Freeman²

2011

“…The deficit in extinction observed in the rats with Purkinje cell loss following OX7-saporin treatment is consistent with the proposed model of extinction. Other mechanisms involved in extinction of eyeblink conditioning including contributions of the hippocampus, and feedback from motor and sensory nuclei in the brain stem (Robleto et al 2004) may have their effects on CR inhibition by influencing Purkinje cells' synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Purkinje cell loss by OX7-saporin impairs acquisition and extinction of eyeblink conditioning

Nolan¹,

Freeman²

2006

The current study examined the effects of globally depleting Purkinje cells in the cerebellar cortex with the immunotoxin OX7-saporin on acquisition and extinction of delay eyeblink conditioning in rats. Rats were given OX7-saporin or saline 2 wk before the start of eyeblink conditioning. The rats that reached a performance criterion of two consecutive days with 80% or greater conditioned responses were given 5 d of extinction training followed by 2 d of reacquisition training. Rats that received infusions of OX7-saporin had 77.2%-97.9% Purkinje cell loss and exhibited impaired acquisition and extinction. The amount of Purkinje cell loss was correlated with the magnitude of the acquisition and extinction impairments. The highest correlations between Purkinje cell number and the rate of acquisition were in lobule HVI and the anterior lobe. The highest negative correlation between Purkinje cell number and the percentage of conditioned responses during extinction was in the anterior lobe. The results indicate that cerebellar Purkinje cells, particularly in the anterior lobe and lobule HVI, play significant roles in acquisition and extinction of eyeblink conditioning.Cerebellar learning is critical for making adaptive adjustments to movements. An early model of cerebellar learning proposed by Albus (1971) suggests that learning-specific changes in synaptic function occur exclusively in the cerebellar cortex. Empirical evidence supporting learning-specific changes in cerebellar cortex initially came from neurophysiological analyses of arm movements and adaptation of the vestibular ocular reflex (Ito 1972;Gilbert and Thach 1977;Ito and Kano 1982). Evidence subsequently emerged that indicated a critical role for learning-specific plasticity in the cerebellar and vestibular nuclei (Miles and Lisberger 1981; McCormick and Thompson 1984a,b). The most prevalent view currently is that learning-specific plasticity occurs in the cerebellar cortex and deep nuclei (Mauk and Donegan 1997;Steinmetz 2000;Christian and Thompson 2003). The computational model of Mauk and colleagues further specifies that plasticity in the cerebellar cortex is critical for initial acquisition and timing of conditioned responses, whereas plasticity in the interpositus nucleus is necessary for long-term storage of a basic (not precisely timed) conditioned response (CR) (Medina et al. 2001;Ohyama and Mauk 2001).The precise role of the cerebellar cortex in eyeblink conditioning has been difficult to establish, due primarily to discrepant findings between laboratories. Some laboratories found that cortical lesions abolished eyeblink CRs, while others found recoverable deficits, depending on lesion size, location, and amount of pre-lesion training (McCormick and Thompson 1984a;Yeo et al. 1985;Lavond et al. 1987;Lavond and Steinmetz 1989;Yeo and Hardiman 1992;Harvey et al. 1993;Perrett et al. 1993;Woodruff-Pak et al. 1993). Moreover, Yeo and colleagues demonstrated that reversible inactivation of cortical activity in HVI and the anterior lobe abolished CRs,...

“…CRs gradually decrease to baseline levels over the course of CS-alone extinction trials, and findings in adult subjects from a number of preparations, including Pavlovian fear and eyeblink conditioning, indicate that extinction is new, inhibitory learning rather than erasure of original learning (Napier et al 1992;Medina et al 2001;Bouton 2004;Robleto et al 2004). Fear conditioning studies in developing rats have shown that extinction at P24 or 25 leads to new learning, consistent with that seen in adult studies, whereas extinction at P17 or 18 may lead to erasure of original learning (Kim and Richardson 2010a).…”

mentioning

confidence: 99%

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

Brown

Freeman

2014

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.