Cerebellar Prediction and Feeding Behaviour

Abstract

Given the importance of the cerebellum in controlling movements, it might be expected that its main role in eating would be the control of motor elements such as chewing and swallowing. Whilst such functions are clearly important, there is more to eating than these actions, and more to the cerebellum than motor control. This review will present evidence that the cerebellum contributes to homeostatic, motor, rewarding and affective aspects of food consumption.Prediction and feedback underlie many elements of eating, as food consumption is influenced by expectation. For example, circadian clocks cause hunger in anticipation of a meal, and food consumption causes feedback signals which induce satiety. Similarly, the sight and smell of food generate an expectation of what that food will taste like, and its actual taste will generate an internal reward value which will be compared to that expectation. Cerebellar learning is widely thought to involve feed-forward predictions to compare expected outcomes to sensory feedback. We therefore propose that the overarching role of the cerebellum in eating is to respond to prediction errors arising across the homeostatic, motor, cognitive, and affective domains.

Keywords: Cerebellum; Feeding behaviour; Hunger; Reward; Satiation.

Fig. 1

Cerebellar anatomical organisation. a Dorsal view of the rat (left) and human (right) cerebellum. There are three main longitudinal compartments of the cerebellar cortex, from medial to lateral the vermis, paravermis and hemisphere. AL, anterior lobe; PL, posterior lobe. b Simplified cerebellar circuitry. Inputs to the cerebellum are from mossy fibres of various pre-cerebellar nuclei and climbing fibres of the inferior olive (IO), both of which are glutamatergic. Mossy fibres synapse onto granule cells (GCs) which form bifurcating axons, known as parallel fibres, targeting Purkinje cell (PC) dendrites, and climbing fibres synapse onto PC dendrites directly. Both mossy fibres and climbing fibres also form collaterals targeting neurons of the cerebellar nuclei (CN). PCs are the sole output neuron of the cerebellar cortex, and these GABAergic neurons target neurons of the CN which form cerebellar output. Several types of interneurons also act within the cerebellar cortex, including molecular layer interneurons (MLIs), not all of which are shown. c Outlines of the rat (left) and human (right) cerebellar nuclei. The vermis, paravermis and hemispheres of the cerebellar cortex project to the fastigial nuclei (FN, also known as medial nuclei), interpositus nuclei (IN) and dentate nuclei (DN, also known as lateral nuclei), respectively. Scaled so that FN is a similar size in both species. Adapted from Altman and Bayer [26]

Fig. 2

Simplified diagram showing cerebellar connections with feeding circuits in the brain. The hypothalamic nuclei are central to a network of brain regions which regulate appetite. Distinct subtypes of neurons in the arcuate (ARC) nucleus of the hypothalamus are involved in the initiation (AgRP neurons) or cessation of food consumption (POMC neurons) via their inputs to the other hypothalamic nuclei including the paraventricular hypothalamic nucleus (PVN), ventromedial hypothalamic nucleus (VMH), lateral hypothalamic nucleus (LH), and dorsomedial hypothalamic nucleus (DMH). Short-term appetite regulation involves the parabrachial nucleus (PBN) and the solitary tract nucleus (NTS) of the brainstem, which respond to feedback from the gut and form connections with the hypothalamus to initiate satiation. The cerebellum has reciprocal connections with the VMH, LH, PBN and NTS, and sends inhibitory projections to the DMH

Fig. 3

Cerebellar and brain-wide networks involved in eating behaviours. a Cerebellar regions shown to be involved in homeostatic (grey), motor (blue), reward (yellow) and affective (purple) aspects of eating. Animal studies are depicted on an outline of the rat cerebellum on the left, and human studies are shown on the right. The numbers correspond to the studies detailed in Table 1. b The cerebellum has connections with brain regions contributing to homeostatic (grey), motor (blue), reward (yellow) and affective (purple) domains of eating behaviours, depicted in a (i) rat and (ii) human brain outline. Connections may be direct or indirect; the latter is the case for cerebello-thalamo-cortical pathways. We propose that the cerebellum has a unifying role via prediction signals which contributes to each of these components. Note that this diagram is not comprehensive, but represents key structures discussed in this review. PFC, prefrontal cortex; VTA, ventral tegmental area; RN, red nucleus; PAG, periaqueductal grey; PBN, parabrachial nucleus; NTS. nucleus tractus solitaries