Changes in complex spike activity during classical conditioning

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.

Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

“…As illustrated in Fig. 3D, the effect was most pronounced in the latter part of the CS, which is consistent with earlier reports (21) and with the known time course of nucleo-olivary inhibition (14,29).…”

“…A central tenet of the model is that the reinforcement value of a paired trial depends on the existing associative strength between the presented stimuli (3,4). Neural mechanisms for several phenomena related to the Rescorla-Wagner model have already been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In this paper, we present evidence from our eyeblink setup that builds on and advances prior thinking regarding the physiological basis of the RescorlaWagner model.…”

“…However, disinhibiting the cerebellar nuclei also leads to inhibition of the inferior olive via the GABAergic nucleo-olivary pathway (6,7,16,38,39). This can be seen by recording field potentials on the cerebellar surface (40,41), or the frequency of spontaneous complex spikes in Purkinje cells, during conditioning (14). Because the inhibition is associated with an unusually long delay (42), it will coincide with the arrival of the US (13), which suggests that the nucleo-olivary pathway is part of a negative-feedback system that controls cerebellar learning (5,16).…”

Cerebellar contributions to motor control and language comprehension: searching for common computational principles

“…How well does the internal model hypothesis match empirical data from neurophysiological experiments? A simple Pavlovian conditioning task, eyeblink conditioning, has served as a model paradigm for studying cerebellar learning . In one version of this preparation, an air puff to the eye serves as the unconditioned stimulus (US), eliciting an instinctive blink (the unconditioned response, UR) to protect the cornea.…”

“…In one version of this preparation, an air puff to the eye serves as the unconditioned stimulus (US), eliciting an instinctive blink (the unconditioned response, UR) to protect the cornea. If this US is repeatedly preceded by a neutral stimulus such as a tone (conditioned stimulus, CS), then the animal will come to blink in anticipation of the US, a conditioned response (CR) . Moreover, with extended training, the dynamics of the CR will be adjusted such that the blink is maximal around the onset time of the airpuff .…”