Abstract
The cerebellar cortex is necessary for adaptively timed conditioned responses (CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause responses or “Purkinje cell CRs” to the conditioned stimuli (CS), resulting in disinhibition of the cerebellar nuclei (CN), allowing them to activate motor nuclei that control eyeblinks. This disinhibition also causes inhibition of the inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO, which relays the unconditional stimulus (US) to the cortex, elicits characteristic complex spikes in Purkinje cells. Although Purkinje cell activity, as well as stimulation of the CN, is known to influence IO activity, much remains to be learned about the way that learned changes in simple spike firing affects the IO. In the present study, we analyzed changes in simple and complex spike firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate ferrets undergoing training in a conditioning paradigm. In agreement with the N-O feedback hypothesis, acquisition resulted in a gradual decrease in complex spike activity during the conditioned stimulus, with a delay that is consistent with the long N-O latency. Also supporting the feedback hypothesis, training with a short interstimulus interval (ISI), which does not lead to acquisition of a Purkinje cell CR, did not cause a suppression of complex spike activity. In contrast, observations that extinction did not lead to a recovery in complex spike activity and the irregular patterns of simple and complex spike activity after the conditioned stimulus are less conclusive.
Highlights
In eyeblink conditioning, repeated pairings of an originally neutral conditional stimulus (CS) and an unconditional, reflexeliciting stimulus (US), results in acquisition of a conditioned response (CR), occurring just before the expected US onset
Purkinje cell CRs are not acquired for interstimulus interval (ISI) below ∼100 ms, and using a 50 ms ISI even causes increased Purkinje cell activity (Wetmore et al, 2014). Is this increase in simple spike frequency associated with a similar increase in complex spike frequency? This study aims to answer these questions by examining the effect of learned changes in Purkinje cell simple spikes on complex spike activity
An additional four cells, which had not been followed during the entire acquisition phase, but which exhibited typical Purkinje cell CRs when found, were included in the extinction dataset
Summary
In eyeblink conditioning, repeated pairings of an originally neutral conditional stimulus (CS) and an unconditional, reflexeliciting stimulus (US), results in acquisition of a conditioned response (CR), occurring just before the expected US onset. This CR can be extinguished by repeatedly presenting the CS alone (Kehoe and Macrae, 2002). Purkinje cells, which provide the sole output from the cerebellar cortex, acquire a pause response, a “Purkinje cell CR” (Figures 1C, 2A,E), that shares many features with learned eyeblinks (Jirenhed et al, 2007; Jirenhed and Hesslow, 2011a,b). Since Purkinje cells are inhibitory, a pause response will cause disinhibition of their target neurons in the cerebellar nuclei (CN; De Zeeuw and Berrebi, 1995), allowing them to initiate a motor response (Hesslow, 1994a; Heiney et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
