Stimulus Generalization of Conditioned Eyelid Responses Produced Without Cerebellar Cortex: Implications for Plasticity in the Cerebellar Nuclei

Abstract

In Pavlovian eyelid conditioning and adaptation of the vestibulo-ocular reflex, cerebellar cortex lesions fail to completely abolish previously acquired learning, indicating an additional site of plasticity in the deep cerebellar or vestibular nucleus. Three forms of plasticity are known to occur in the deep cerebellar nuclei: formation of new synapses, plasticity at existing synapses, and changes in intrinsic excitability. Only a cell-wide increase in excitability predicts that learning should generalize broadly from a training stimulus to other stimuli capable of supporting learning, whereas the alternatives predict that learning should be relatively specific to the training stimulus. Here we show that deep nucleus plasticity, as assessed by conditioned eyelid responses produced without input from the cerebellar cortex, is relatively specific to the training conditioned stimulus (CS). We trained rabbits to a tone or light CS with periorbital stimulation as the unconditioned stimulus (US), and pharmacologically disconnected the cerebellar cortex during a posttraining generalization test. The short-latency conditioned responses unmasked by this treatment showed strong decrement along the dimension of auditory frequency and did not generalize across stimulus modalities. These results cannot be explained solely by a cell-wide increase in the excitability of deep nucleus neurons, and imply that an input-specific mechanism in the deep cerebellar nucleus operates as well.Several examples of motor learning including Pavlovian eyelid conditioning and adaptation of the vestibulo-ocular reflex require the cerebellum, and the relevant plasticity appears to occur in the cerebellar cortex and the deep cerebellar or vestibular nuclei

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.…”

“…Thus, the stimulus specificity cannot be attributed to an inability of the white noise to gain access to the AIN. The data suggest that a highly input-specific form of plasticity in the AIN underlies SLRs (Perrett and Mauk, 1995;Ohyama et al, 2003).…”

“…A pairing-specific increase in the number of excitatory synapses in the AIN (Kleim et al, 2002) and/or long-term potentiation (LTP) at the mossy fiber-to-AIN synapse (Racine et al, 1986;Pugh and Raman, 2006) have been reported. Persistent increases in the intrinsic excitability of deep cerebellar nucleus neurons (Aizenman and Linden, 2000;Nelson et al, 2003Nelson et al, , 2005Zhang et al, 2004) could also contribute, but such changes must be region specific (Zhang and Linden, 2003) to explain the stimulus specificity of SLRs (Perrett and Mauk, 1995;Ohyama et al, 2003).…”

“…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.…”

Cerebellar Cortex Contributions to the Expression and Timing of Conditioned Eyelid Responses

“…1, A, left, and B; P Ͼ 0.05). Lidocaine infusions unmasked shortlatency responses similar to those produced after lesions of cerebellar cortex or infusions of the GABA A receptor antagonists picrotoxin or gabazine into the DCN (Bao et al 2002;Garcia and Mauk 1998;Medina et al 2000aMedina et al , 2001Ohyama et al , 2003aPerrett and Mauk 1995;Perrett et al 1993) (Fig. 1, A , middle, and B, bottom).…”