The inferior olive generates complex spikes at the cerebellar Purkinje neurons by way of the climbing fibres, and these spikes are real-time event signals (Ekerot, Schouenborg et al. 1987; Hasanbegović 2024; Sendhilnathan and Goldberg 2020a; Watson, Apps et al. 2013). Each climbing fibre innervates from 1 to 10 Purkinje neurons and every Purkinje neuron is connect to but one climbing fibre, which allows a single climbing fibre to have control over the plasticity at a Purkinje neuron (Eccles et al. 1967; Gibson et al. 2004; Ito 2008; Rawson and Tilokskulchai 1981). The inferior olive receives input from the neocortex, brain stem, and spinal cord, as does the cerebellar cortex (Eccles et al. 1967; Ekerot, Schouenborg et al. 1987; Hasanbegović 2024; Loyola et al. 2019; Sladek and Bowman 1975; Watson, Apps et al. 2013). Low-frequency stimulation of the climbing fibres of the inferior olive at 10 Hz reduces the firing of simple spikes of a Purkinje neuron to zero (Rawson and Tilokskulchai 1981). The stimulation produces complex spikes at the Purkinje neurons which forecloses the possibility of any simple spikes being generated. Under neutral conditions, the complex-spike rate is about 2 Hz such that at lower frequencies the rate of simple spikes is increased, whereas at higher frequencies the rate of simple spikes is decreased (Bell et al. 1997; De Zeeuw 2021; Gallistel et al. 2022; Giovannucci et al. 2017; Loyola et al. 2019; Shadmehr 2020; Tehovnik et al. 2021; Wang et al. 2023; Zhou et al. 2014). This relationship is used to increase and decrease the simple-spike rate thereby altering the gain of a behavior, which optimizes and automates a response and which is the goal of learning (the purpose of which is to minimize energy expenditure during task execution, Lehericy et al. 2005).
During the generation of volitional acts such as walking, running, swimming, and so on, namely during Vanderwolf’s type I behavior (which is accompanied by theta activity, Tehovnik 2017; Vanderwolf 1969), the pathway between the inferior olive and the cerebellar Purkinje neurons is disabled (Apps 1999; Armstrong et al. 1988; Carli et al. 1967; Gellman et al. 1985; Smith and Chapin 1996). What this indicates is that alterations to the gain at Purkinje neurons must occur during Vanderwolf’s type II behavior, e.g., during behavioral pauses (immobility). Note that this is also the time during wakefulness when declarative conscious memories are stored (Logothetis et al. 2012; Ólafsdóttir et al. 2017; Wilson and McNaughton 1994; Yu et al. 2017), suggesting that information consolidation at the cerebellum and neocortex occur during pauses in behavior.
The climbing fibres carry event information such as the onset of pain (Ekerot, Schouenborg et al. 1987; Watson, Apps et al. 2013), retinal slip (Miles and Lisberger 1981), unconditioned responses (Gallistel et al. 2022; Swain, Thompson et al. 2011), reward delivery (Hasanbegović 2024; Sendhilnathan and Goldberg 2020) or an electrical command pulse (in electric fishes, Fukutomi, Carlson 2020). All these events can be associated with various sensory-motor items via cerebellar simple/complex spike plasticity. Pain evokes a context specific avoidance response, changes in retinal slip change the gain of the vestibulo-ocular reflex, unconditioned responses are paired with conditioned responses, a reward shapes operant behavior, and an electrical pulse is paired with perturbations of the electric field (for communication and the identification of objects by electric fishes). Even something as basic as micturition, defecation, or breathing while learning to speak needs to be configured by cerebellar Purkinje neurons during infant development (Zhu, Wang et al. 2006; note that drivers for respiration/breathing are found in the inferior olive, Nattie 1999 ).
We would suggest that for all associations, the neocortex (which stores declarative conscious information) must be engaged to initiate cerebellar plasticity, which is consistent with the work of Kennedy et al. (1966). For example, it is known that damage to the frontal eye fields and superior colliculus (which abolishes all visually guided saccades by disconnecting the neocortex from the brain stem) fixes the gain of the vestibulo-ocular reflex, such that it can no longer be changed, since to re-calibrate the vestibulo-ocular reflex the gain-change would be interrupted by abolition of the fast-phase of the response (Schiller and Tehovnik 2015). We suspect a similar deficit would occur if the frontal eye fields and the medial temporal cortex/medial superior temporal cortex (area MT/MST) were damaged thereby abolishing the slow phase of the response (i.e., by disrupting smooth pursuit, Dürsteler and Wurtz 1988; Gottlieb, Bruce et al. 1993, 1994; Komatsu and Wurtz 1989; Tehovnik et al. 2000). Accordingly, as suspected by Ivan Pavlov (1927) and later by Donald Hebb (1949), all learning is dependent on the neocortex, and we now know that this dependency is based on an intimate cooperation between the neocortex and the cerebellum (Hasanbegović 2024).
- Badges
- Science topic
- Similar topics
- Methodology
- Research Methodology
- Research Papers