A Mechanism for Savings in the Cerebellum

Abstract

The phenomenon of savings (the ability to relearn faster than the first time) is a familiar property of many learning systems. The utility of savings makes its underlying mechanisms of special interest. We used a combination of computer simulations and reversible lesions to investigate mechanisms of savings that operate in the cerebellum during eyelid conditioning, a well characterized form of motor learning. The results suggest that a site of plasticity outside the cerebellar cortex (possibly in the cerebellar nucleus) can be protected from the full consequences of extinction and that the residual plasticity that remains can later contribute to the savings seen during relearning.Key words: plasticity; learning; memory; eyelid conditioning; simulation; LTD; LTP; extinction Riding a bicycle, playing the piano, and typing are examples of motor skills that illustrate our capacity for relearning that is much more rapid than the original learning. In the laboratory, this rapid relearning is known as savings and has been frequently studied in the context of Pavlovian conditioning of motor responses. During conditioning of eyelid responses for example, paired presentations of a tone [the conditioned stimulus (CS)] and a reinforcing unconditioned stimulus (US), such as periorbital electrical stimulation, promote the acquisition of a conditioned motor response (closing the eyelid in response to the tone). These conditioned responses can be unlearned during extinction training in which the CS is not paired with the US (Schneiderman et al., 1962). During reacquisition training, savings is apparent because relearning occurs much faster than original learning (Frey and Ross, 1968;Napier et al., 1992). The existence of savings is among the evidence supporting the notion that extinction training leaves behind residual excitatory strength (Reberg, 1972;Schactman et al., 1985;Kehoe, 1988). Here we present evidence for this residual-plasticity hypothesis in eyelid conditioning and characterize basic mechanisms involved in the savings observed with this form of motor learning.A variety of evidence indicates that the cerebellum is a necessary component of the neural pathways that mediate eyelid conditioning (Thompson, 1986;Thompson and Krupa, 1994;Raymond et al., 1996;Kim and Thompson, 1997). This evidence, combined with the well characterized synaptic organization and physiology of the cerebellum (Eccles et al., 1967;Llinas, 1981;Ito, 1984;Voogd and Glickstein, 1998), makes it possible to build large-scale computer simulations of the cerebellum and to test their capacity to display eyelid conditioning. We have shown previously that, by incorporating the evidence for plasticity at two sites (one in the cerebellar cortex and one in the cerebellar interpositus nucleus), these simulations can emulate the acquisition and extinction of conditioned responses (Medina et al., 2000). Here we report that these same simulations also display savings, even after extensive extinction training. In the simulations, the rules for plasticity combine...

Learning-Induced Plasticity in Deep Cerebellar Nucleus

“…Consistent with previous studies, we observed no SLRs before training (Fig. 6 B, T1) (Medina et al, 2001;Ohyama et al, 2003). Five sessions of unpaired training failed to promote learning and, importantly, also failed to support the acquisition of SLRs (Fig.…”

“…First, infusing picrotoxin into the AIN at different time points during initial acquisition reveals that the probability of observing SLRs parallels that of normal conditioned responses, consistent with the notion that plasticity induction in the AIN is the rate limiting factor in acquisition (Medina et al, 2001). Second, the observation of initial learning in the cerebellar cortex that is later revealed by inducing AIN plasticity suggests that AIN plasticity is necessary for the expression of conditioned responses and requires initial plasticity in the cerebellar cortex for its induction (Ohyama and Mauk, 2001).…”

“…Third, the hypothesis explains a form of savings, the rapid reacquisition of learned eyelid responses after extinction (Kehoe, 1988). Consistent with a detailed simulation of the cerebellum, SLRs unmasked by picrotoxin in the AIN are more resistant to extinction than normal conditioned responses, and their frequency predicts the rate of subsequent relearning (Medina et al, 2001). This suggests that initial acquisition of eyelid responses is slow, because it requires establishing plasticity at two sites, whereas relearning after extinction is faster, because plasticity is already induced in the AIN.…”

“…As with a tone-CS, this unmasked SLRs to the mossy fiber stimulation CS (Fig. 5, A previous study showed that SLRs are unmasked by disconnection of the cerebellar cortex even when conditioned responses have been fully extinguished by repeated presentations of the tone-CS alone (Medina et al, 2001). To ensure that SLRs supported by mossy fiber stimulation display properties similar to those supported by a tone-CS, we performed a second gabazine infusion after at least four sessions of extinction.…”

“…Early results in rabbits ranged from complete abolition of the learned responses pointing to the cerebellar cortex as the key site (Yeo, 1991) to nominal effects that suggested a more fundamental role for the AIN (McCormick and Thompson, 1984). Numerous subsequent studies measuring closure of the external eyelid or nictitating membrane have reported responses with relatively fixed and short latencies to onset (ϳ80 -150 ms) after direct lesions (McCormick and Thompson, 1984;Perrett et al, 1993;Perrett and Mauk, 1995;Garcia et al, 1999;Medina et al, 2000) or infusing GABA A antagonists into the AIN (Garcia and Mauk, 1998;Medina et al, 2001;Ohyama and Mauk, 2001;Bao et al, 2002;Ohyama et al, 2003;Aksenov et al, 2004). We previously hypothesized that these short-latency responses (SLRs) (see Fig.…”