The neurophysiology of express oculo- and skeleto-motor behavior of primates has received renewed interest in systems neuroscience (e.g., Cecala, Corneil et al. 2023; Ito, Maldonado et al. 2022; Mekhaiel, Goodale et al. 2023). This interest is driven by the need to determine the critical brain circuits involved in establishing automaticity. The notion that the subcortical structure, the superior colliculus, is necessary for this process and that it relays sensory-cortical information from posterior regions of the neocortex to the brain stem is not in dispute (Schiller and Tehovnik 2015; for a recent review see Tehovnik 2024). The subcortical circuits that finalize all automated behavior awaits clarification, however.

The cerebellar Purkinje neurons establish an efference copy representation of automated motor responses for such behaviors as movement of the head to trigger VOR or presentation of a visual stimulus for triggering express saccades (Lisberger 1984; Miles and Lisberger 1981; Tehovnik 2024; Tehovnik, Hasanbegović, Chen 2024; Tehovnik, Patel, Tolias et al. 2021). Indeed, the Purkinje channel is important to the mediation of automated motor responses. The best evidence for this comes from the establishment of associations using classical conditioning, after an animal is overtrained on conditioning (Gallistel et al. 2022).

A brief review of the circuit mediating classical conditioning is required (see Fig. 1, from Fig. 1B of Gallistel et al. 2022). Once conditioning is established between a conditioned stimulus (CS) and an unconditioned stimulus (UCS) there is an immediate drop in discharge by the Purkinje neurons; this drop evokes an eyeblink well before the delivery of an unconditioned stimulus. Figure 2 shows the pattern of Purkinje firing once conditioning has been well programmed, such that the conditioned stimulus alone evokes an eyeblink (Fig. 2, from Fig. 2AB of Gallistel et al. 2022). Across the 20 trials illustrated, notice that the latency to evoke a drop in firing oscillates from a low value of 30 ms to a high value of about 100 ms. The figure shows at least three cycles of oscillation, such that every 8 trials a full range of latencies is exhibited by the neuron. The reason this oscillatory pattern is important (a pattern exhibited by overtrained, conditioned Purkinje neurons) is that it maps on to the latency of the behavioral response. As well, when subjects are overtrained on either VOR or on express saccades it is noteworthy that a similar oscillation of behavioral latencies occurs across trials, which can be grouped in blocks of 8 trials or so (Lisberger 1984; Tehovnik, Hasanbegović, Chen 2024). For example, in the case of express saccades (with latencies < 125 ms) versus regular saccades (with latencies > 125 ms), the two saccade types (which are bimodally distributed) are mixed across trials thereby revealing an oscillatory pattern (Schiller and Tehovnik 2015).

We propose that the oscillatory pattern reflects the utilization of a minimal and maximal circuit through the cerebellum used to reinforce automaticity. For the minimal-latency circuit (i.e., short-latency Purkinje discharge), there is a synchronization of transmission through the Purkinje-interpositus and direct-interpositus synapses to induce a combined EPSP at an interpositus neuron. For the maximal-latency circuit, there is no synchronization: the Purkinje-interpositus EPSP will follow the direct interpositus EPSP. The timing of the latter, the direct interpositus EPSP should remain invariant once an animal is overtrained. You might ask: why build a system with such checks and balances? This is to make sure that the Purkinje circuit is always up to date about the latest change to any behavioral program. The worst thing that can happen is to be executing an automated act once that act becomes behaviorally obsolete. This can lead to the death of an animal or fellow animal, e.g., when Alec Baldwin discharged a gun that he believed was not loaded, which resulted in the death of his colleague.

The idea that a minimal circuit (i.e., a cerebellar nuclear circuit only) is sufficient for the execution of automated acts comes from three studies. Disruption of just the Purkinje neurons (while sparing the cerebellar nuclei) affects only the learning of a new VOR gain or a new visual-object-response association while sparing the execution of all old associations (Kassardjian et al. 2005; Sendhilnathan and Goldberg 2020b). However, damage of both the Purkinje neurons and the cerebellar nuclei abolishes all learned behavior, new and old, using an eyeblink conditioning paradigm (Takahara et al. 2003).

The foregoing needs to be verified beyond a doubt. This will require the simultaneous recording of both Purkinje neurons and cerebellar nuclear neurons, as an animal learns new routines and as it is made to express overlearned routines. Furthermore, the effects of paired Purkinje lesions and nuclear lesions will need to be compared to those of individual Purkinje or nuclear lesions for an assortment of behavioral paradigms.

Figure 1: The basic circuit for the conditioning of an eyeblink response in mammals (i.e., in the ferret). Top inset illustrates what happens to a Purkinje neuron (Pc) before and after conditioning. After conditioning with a 300-ms conditioning pulse a Purkinje neuron stops firing; this event causes a cerebellar interpositus (AIN) neuron to increase in discharge. This increase is conveyed polysynaptically to the eyelids to induce an eyeblink. Other labels in the figure: climbing fibres (cf), anterior interpositus neurons (AIN), mossy fibres (mf), granular cells (Grc), parallel fibres (pf), and golgi cell (Gc). From Fig. 1B of Gallistel et al. (2022).

Figure 2: Raster data are shown for one Purkinje neuron whose discharge is abruptly terminated after a conditioned stimulus (the delivery of an electric shock to the ipsilateral paw) in the absence of the unconditioned stimulus (i.e., stimulation of the climbing fibres—see Fig. 1, fibre in red—that innervate both Purkinje neurons and interpositus neurons). (A) A total of 20 trials are illustrated. The first blue bar indicates the onset of the conditioned stimulus, and the second blue bar indicates its offset. The green marker indicates the termination of discharge, and the red marker indicates the resumption of discharge. (B) Show the cumulative histogram of the discharge above for the 20 trials. From Fig. 2AB of Gallistel et al. (2022).