Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Abstract

Aim:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). Methods: The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US). A high-resolution potentiometer was used to monitor eyeblink responses. Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4), during which microinjections of muscimol, a GABA A receptor agonist, were performed to reversibly inactivate the cerebellum unilaterally prior to training. To test whether any learning had occurred during these inactivation sessions, training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation. Results: Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4, and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7. In contrast, animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4, although their CR acquisition was significantly retarded during session 2. In addition, microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity. Finally, microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR). Conclusion: In contrast to the essential role of the ipsilateral cerebellum, the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.

Spontaneous Behavior in Noise and Silence: A Possible New Measure to Assess Tinnitus in Guinea Pigs

“…It has been shown that guinea pigs can generalize this response to other sound levels and to intracochlear electrical stimulation ( 17 , 19 ). Guinea pigs can also be trained to respond to pure tones, although in different training paradigms ( 21 – 25 ). In spite of these positive findings, training guinea pigs to respond to silent intervals (CS) in noise was unsuccessful, both in naïve and previously trained animals.…”

Medial Prefrontal Cortex–Pontine Nuclei Projections Modulate Suboptimal Cue-Induced Associative Motor Learning

“…Moreover, for optogenetic activation of the bilateral caudal mPFC and of its axon terminals in the PN, rats were bilaterally microinjected with 0.5 µL of pAAV 2/9-CaMKIIα-ChR2(H134R)-mCherry (Virus titers: 1.35 × 10 13 GC/mL) or pAAV 2/9-CaMKIIα-mCherry (Virus titers: 1.25 × 10 13 GC/mL) into both left and right caudal mPFC (AP + 1.92 mm, ML ± 0.9 mm, DV − 3.0 mm; Figs 3A,B and 5A,B). In addition, previous studies have shown that the mPFC projects bilaterally to the PN, which then projects predominantly to the contralateral cerebellum, and that only the ipsilateral cerebellum (relative to the US presented eye) is required for EBC (Hu et al 2009;Moya et al 2014). Thus, for direct optogenetic activation of the PN cell bodies, rats were unilaterally microinjected with 0.5 µL of pAAV 2/9-hSyn-ChR2(H134R)-mCherry (Virus titers: 5.18 × 10 12 GC/mL) or pAAV 2/9-hSyn-mCherry (Virus titers: 7.04 × 10 12 GC/mL) into the right PN (AP −7.32 mm, ML 0.9 mm, DV −10.0 mm; i.e., contralateral to the training eye) (Fig.…”