Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus

Abstract

Classical conditioning of skeletal muscle responses was accomplished by pairing microstimulation of the pontine nuclei as a conditioned stimulus (CS) with microstimulation of the dorsal accessory olive as an unconditioned stimulus (US). A conditioned response identical in form to the behavioral response elicited by the olivary stimulation was established when the CS was forward paired with the US, and behavioral extinction occurred with CS-alone presentations or unpaired CS-US presentations. Conditioned responding could not be established or maintained when the CS and US were simultaneously presented or when the US preceded the CS (i.e., backward paired). Complete lesions of the interpositus nucleus abolished both conditioned and unconditioned responses. These findings support the idea that plasticity associated with classical conditioning of skeletal muscle responses occurs in regions of the cerebellum that receive convergent CS and US input.

Learning-Induced Plasticity in Deep Cerebellar Nucleus

“…Consistent with previous studies, mossy fiber stimulation supported robust learning (Fig. 5, top) (n ϭ 4; F (4,12) ϭ 18.2; p Ͻ 0.001) (Steinmetz et al, 1989;Hesslow et al, 1999). In an initial test session to confirm proper cannula placement, we infused muscimol to silence the AIN.…”

“…5). Therefore, both SLRs and normal conditioned responses are learned during red nucleus inactivation (Krupa et al, 1993) and with mossy fiber stimulation as the CS (Steinmetz et al, 1989;Hesslow et al, 1999). [It is unlikely that plasticity in a pathway downstream of the AIN that initially bypasses the red nucleus (e.g., via thalamus, cortex, and back to red nucleus) or presynaptic plasticity (e.g., increased transmitter release) in the red nucleus mediates SLRs, because the threshold for evoking eyelid closure by stimulating the AIN does not change with training (Tracy et al, 1998).]…”

“…One such instance is eyelid conditioning, in which repeatedly presenting a tone conditioned stimulus (CS) together with mild electrical stimulation around the eye [the unconditioned stimulus (US)] promotes learning of a well-timed closure of the eyelid in response to the CS. The CS and US are conveyed to the cerebellum, respectively, by mossy and climbing fiber afferents (Mauk et al, 1986;Steinmetz et al, 1989;Hesslow et al, 1999), and the learned eyelid closure is driven by activity in the anterior interpositus nucleus (AIN) of the cerebellum (McCormick and Thompson, 1984;Choi and Moore, 2003) (see Fig. 1).…”

Synapse formation is associated with memory storage in the cerebellum

“…First, the eyeblink CR can be elicited by presentations of just the CS (25) and the onset of the CR precedes the onset of the US. These observations suggest that the memory trace is activated by stimulating the CS pathway (mossy fibers).…”

Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

“…The necessary and sufficient circuitry for excitatory eyeblink conditioning exists within the brainstem and cerebellum. The CS pathway includes mossy fiber projections from the pontine nuclei to the cerebellum (Gould, Sears, & Steinmetz, 1993;Lewis, LoTurco, & Solomon, 1987;Solomon, Lewis, LoTurco, Steinmetz, & Thompson, 1986;Steinmetz, Lavond, & Thompson, 1985;Steinmetz, Rosen, Chapman, Lavond, & Thompson, 1986;Steinmetz, Logan, Rosen, Thompson, Lavond, & Thompson, 1987;Steinmetz, Lavond & Thompson, 1989;Steinmetz, 1990;Tracy, Thompson, Krupa, & Thompson, 1998). The US pathway includes climbing fiber projections from the inferior olive to the cerebellum (De Zeeuw, Van Alphen, Hawkins, & Ruigrok, 1997;Gould et al, 1993;Mauk, Steinmetz & Thompson, 1986;McCormick, Steinmetz, & Thompson, 1985;Steinmetz et al, 1989;Yeo, Hardiman, & Glickstein, 1986).…”