Red Nucleus Neurons Actively Contribute to the Acquisition of Classically Conditioned Eyelid Responses in Rabbits

Abstract

The red nucleus (RN) is a midbrain premotor center that has been suggested as being involved in the acquisition and/or performance of classically conditioned nictitating membrane/eyelid responses. We recorded in rabbits the activity of RN and pararubral neurons during classical eyeblink conditioning using a delay paradigm. Neurons were identified by their antidromic activation from contralateral facial and accessory abducens nuclei and by their synaptic activation from the ipsilateral motor cortex (MC) and the contralateral cerebellar interpositus (IP) nucleus. For conditioning, we used a tone as a conditioned stimulus (CS) followed 250 ms later by a 100 ms air puff as an unconditioned stimulus (US) coterminating with it. Conditioned responses (CRs) were determined from the evoked changes in the electromyographic activity of the orbicularis oculi (OO) muscle. Recorded neurons were classified by their antidromic activation and by their changes in firing rate during the CS-US interval. Identified neurons increased their firing rates in relation to the successive conditioning sessions, but their discharge rates were related more to the EMG activity of the OO muscle than to the learning curves. Reversible inactivation of the IP nucleus with lidocaine during conditioning evoked a complete disappearance of both conditioned and unconditioned eyelid responses, and a progressive decrease in CR-related activity of RN neurons. In contrast, MC inactivation evoked a decrease in the acquisition process and an initial disfacilitation of neuronal firing (which was later recovered), together with the late appearance of CRs. Thus, RN neurons presented learning-dependent changes in activity following MC inactivation.

What we do not know about cerebellar systems neuroscience

“…Specific regions in the C3 zone have been identified as the link in the conditioned eyeblink response (Jirenhed et al, 2007 ). Similar to the motor effects observed by Horn et al ( 2010 ) eyeblink resposes of the C3 zone are relayed by the anterior interposed nucleus and the contralateral red nucleus (Morcuendo et al, 2002 ; Pacheco-Calderón et al, 2012 ). In the rat the relay is a separate population of neurons in the dorsolateral red nucleus and the adjoining pararubral area with projections to the facial motor nucleus (Ruigrok and Cella, 1995 ).…”

Contribution of cerebellar loops to action timing

“…Notably, recording studies have shown that during eyeblink conditioning, pauses in Purkinje cells responses promote bursts of activity in deep cerebellar nuclear neurons (Fig. 2), which drive the conditioned eyeblink response via the red nucleus [40–44]. These pauses (for Purkinje cells) and bursts (cerebellar nuclear neurons) are modified via conditioning to generate the temporal structure of the eyeblink response [45], while convergent motor inputs to downstream brainstem circuitry regulates other movement parameters [44].…”

Effect of transcranial direct current stimulation on semantic discrimination eyeblink conditioning

“…Based on research in animals, it is well established that learning in eyeblink conditioning is a primarily dependent on the cerebellum [4,5]. In addition, several other areas such as the red nucleus [6], thalamus [7], and the somato-sensory cortex [8] participate in regulating eyeblink conditioning. Furthermore, as the task difficulty increases, learning becomes more dependent on the modulatory effects of cerebral structures, most notably the hippocampus [9,10] and the prefrontal cortex [11,12].…”

“…The error bars represent +/− SEM.lyzed using repeated measures analysis of variance (rmANOVA) with Group (sham vs. real) as the between-subjects factor and Block(1)(2)(3)(4)(5)(6)(7)(8) and Trial Type (CS+ vs. CS−) as within-subjects factors.…”