Cerebellar Cortex Lesions Prevent Acquisition of Conditioned Eyelid Responses

Abstract

We have used aspiration and electrolytic lesions to investigate the contributions of cerebellar cortex to the acquisition and expression of conditioned eyelid responses. We show that lesions of the anterior lobe of rabbit cerebellar cortex disrupt the timing of previously learned conditioned eyelid responses. These short-latency responses were used as an indication that the cerebellar cortex was sufficiently damaged and that the underlying pathways necessary for the expression of responses were sufficiently intact to support responses. Rabbits were subsequently trained for 15 daily sessions using a new conditioned stimulus. Whereas rabbits in which lesions had no significant effect on response timing showed rapid acquisition of appropriately timed eyelid responses to the new conditioned stimulus, animals with lesions that disrupt timing showed no significant increases in either amplitude or probability of responses. Histological analysis suggests that damage to the anterior lobe of the cerebellar cortex is necessary and sufficient to abolish timing and prevent acquisition. These data indicate that the cerebellar cortex is necessary for the acquisition of conditioned eyelid responses and are consistent with the hypotheses that (1) eyelid conditioning results in plasticity in both the anterior lobe of the cerebellar cortex and in the anterior interpositus nucleus and (2) induction of plasticity in the interpositus requires intact input from the cerebellar cortex.

Cerebellum volume and eyeblink conditioning in schizophrenia

“…The present results suggest that this acquisition deficit may be associated with structural abnormalities of the anterior cerebellum. This is in agreement with non-human studies showing that lesions to anterior cerebellum disrupt CR acquisition (Lavond and Steinmetz, 1989;Garcia et al, 1999). In fact, Garcia and colleagues (1999) contend that the anterior cortex is necessary for the acquisition/learning of novel paired CS-US relationships.…”

“…In terms of anterior cerebellum influences on CR timing, these data are in agreement with nonhuman studies showing that Purkinje cells in the anterior cerebellum, whose efferents target the interpositus nucleus, have a distinct pattern of activation followed by inhibition after the onset of a CS (Green and Steinmetz, 2005) and ablation of these cells causes timing disruptions of the CR Thompson, 1984b, Parrett et al, 1993;Garcia et al, 1999). The findings unique to the control group data also are in accord with a study by Gerwig et al (2005) showing that anterior cerebellar damage is associated with short CR onset latencies.…”

“…Inhibitory projections from Purkinje cortical neurons modulate the activity of the interpositus, effectively manipulating the timing of the CR (Mamounas et al, 1987;Bao et al, 2002). Evidence suggests that one locus of CR timing modification is the anterior regions of cerebellar cortex (Green and Steinmetz, 2005), an area wherein lesions disrupt CR onset and peak latencies (McCormick and Thompson, 1984b;Logan, 1991;Perrett et al, 1993;Garcia et al, 1999) and, perhaps, CR acquisition (Lavond and Steinmetz, 1989;Garcia et al, 1999). Other studies have implicated the posterior cerebellar cortex in CR acquisition, but with a limited role in the timing of the CR (e.g., Attwell, Rahman, and Yeo, 2001).…”

“…A fairly consistent finding among recent studies has been earlier CR onset and peak latencies (Sears et al, 2000;Brown et al, 2005;see Marenco et al, 2003, for an exception). In the non-human literature, CR onset and CR peak latencies have been associated with anterior cerebellum dysfunction Garcia et al, 1999;Green and Steinmetz, 2005). Although additional research will be necessary to determine the impact of clinical state, medication status, and methodological manipulations on EBC in schizophrenia, there is evidence suggesting that schizophrenia may be associated with cerebellar dysfunction.…”

Learning-Induced Plasticity in Deep Cerebellar Nucleus

“…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.…”