Brain-wide dynamics linking sensation to action during decision-making.

Perceptual decisions rely on learned associations between sensory evidence and appropriate actions, involving the filtering and integration of relevant inputs to prepare and execute timely responses. Despite the distributed nature of task-relevant representations, it remains unclear how transformations between sensory input, evidence integration, motor planning and execution are orchestrated across brain areas and dimensions of neural activity. Here we addressed this question by recording brain-wide neural activity in mice learning to report changes in ambiguous visual input.

Feedback inhibition underlies new computational functions of cerebellar interneurons.

The function of a feedback inhibitory circuit between cerebellar Purkinje cells and molecular layer interneurons (MLIs) was defined by combining optogenetics, neuronal activity recordings both in cerebellar slices and in vivo, and computational modeling. Purkinje cells inhibit a subset of MLIs in the inner third of the molecular layer. This inhibition is non-reciprocal, short-range (less than 200 μm) and is based on convergence of one to two Purkinje cells onto MLIs.

Cerebellar implementation of movement sequences through feedback.

Most movements are not unitary, but are comprised of sequences. Although patients with cerebellar pathology display severe deficits in the execution and learning of sequences (Doyon et al., 1997; Shin and Ivry, 2003), most of our understanding of cerebellar mechanisms has come from analyses of single component movements.

Cerebellar Processing Common to Delay and Trace Eyelid Conditioning.

Results from previous lesion studies have been interpreted as evidence that the cerebellar cortex plays different roles for delay and trace conditioning of eyelid responses. However, the cerebellar cortex is organized by parasagittal stripes of Purkinje cells (PCs) that converge onto common deep nucleus neurons and receive common or related climbing fiber inputs. Based on this organization, we hypothesized that cerebellar tasks involving the same response system, such as delay and trace eyelid conditioning, would engage the same PCs and that the relationships between PC activity and expression of behavioral responses would be similar for both tasks.

A cerebellar adaptation to uncertain inputs.

Noise and variability are inherent and unavoidable features of neural processing. Despite this physiological challenge, brain systems function well, suggesting the existence of adaptations that cope with noise. We report a novel adaptation that the cerebellum implements to maintain correct responses in the face of ambiguous inputs.

Links Between Single-Trial Changes and Learning Rate in Eyelid Conditioning.

The discovery of single-trial learning effects, where the presence or absence (or the number) of climbing fiber inputs produces measureable changes in Purkinje cell response and in behavior, represents a major breakthrough in cerebellar learning. Among other things, these observations provide strong links between climbing fiber-mediated plasticity and cerebellar learning. They also demonstrate that cerebellar learning is stochastic, with each instantiation of a movement producing a small increment or decrement in gain.

Relating cerebellar purkinje cell activity to the timing and amplitude of conditioned eyelid responses.

How Purkinje cell (PC) activity may be altered by learning is central to theories of the cerebellum. Pavlovian eyelid conditioning, because of how directly it engages the cerebellum, has helped reveal many aspects of cerebellar learning and the underlying mechanisms. Theories of cerebellar learning assert that climbing fiber inputs control plasticity at synapses onto PCs, and thus PCs control the expression of learned responses.

Cerebellar mechanisms of learning and plasticity revealed by delay eyelid conditioning.

The analysis of well-defined behaviors that require the cerebellum has helped reveal many key mechanisms operating in the cerebellum to mediate learning and feed-forward prediction. These systems include eyelid conditioning, adaptation of the vestibuloocular reflex, smooth pursuit eye movements, and arm-reaching tasks. This review focuses specifically on the variety of findings that have come from the use of eyelid conditioning to study the cerebellum.