Negative motivational control of saccadic eye movement by the lateral habenula

Abstract

Reward is crucial for survival of animals and influences animal behaviours. For example, an approaching behaviour to reward is more frequently and quickly elicited when a big reward is expected than when a small reward is expected. Midbrain dopamine neurons are thought to be crucial for such reward-based control of motor behaviour. Indeed, dopamine neurons are excited by cues predicting reward and inhibited by cues predicting no-reward. These excitatory and inhibitory signals would then be used for enhancing and depressing sensorimotor processing, respectively, in the brain areas targeted by dopamine neurons (e.g., striatum). However, it was unknown which parts of the brain provide dopamine neurons with reward-related signals necessary for their responses. We recently showed evidence that the lateral habenula transmits reward-related signals to dopamine neurons, especially to inhibit dopamine neurons. This recent study suggested that the lateral habenula suppresses less rewarding saccadic eye movements by inhibiting dopamine neurons. In the present review, we first summarize anatomical and functional aspects of the lateral habenula. We will then describe our own study. Finally, we will discuss how the lateral habenula, as well as dopamine neurons, contributes to the reward-based control of saccadic eye movements.

Figure 1

(A) Scheme showing the location of the lateral habenula and its afferent and efferent connections in a parasagittal section of the macaque brain. Acc, nucleus accumbens; DB, diagonal band of Broca; DR, dorsal raphe; fr, fasciculus retroflexus; GPi, globus pallidus internal segment; LH, lateral hypothalamus; LHb, lateral habenula; MPFC, medial prefrontal cortex; MR, medial raphe; sm, stria medullaris; SNc, substantia nigra pars compacta; VP, ventral pallidum; VTA, ventral tegmental area. (B) Sequence of events in the visually guided saccade task. (C) Distribution of saccade latencies in reward trials (black) and in no-reward trials (gray) in one example monkey. Modified from Nature (Matsumoto and Hikosaka, 2007).

Figure 2

(A) and (B) Averaged activity of lateral habenula neurons (A, n=43) and dopamine neurons (B, n=62) during the visually guided saccade task with positional reward bias. Spike density functions (SDFs) are aligned at the onset of target (left) and at the onset of outcome (right). The SDFs are shown for reward trials (black) and no-reward trials (gray). Continuous curves indicate activity in trials excluding the first trials after the reversal of rewarded direction. Dotted curves indicate activity in the first trials. The data from ipsilateral and contralateral saccades are combined. (C) A hypothetical scheme showing the role of the lateral habenula in reward-based control of saccadic eye movements. CD, caudate nucleus; DA, dopamine neurons; FEF, frontal eye field; PF, prefrontal cortex; SC, superior colliculus; SEF, supplementary eye field; SNr, substantia nigra pars reticulata. Excitatory and inhibitory connections are indicated by (+) and (-), respectively. It is unknown whether lateral habenula neurons themselves are inhibitory. Modified from Nature (Matsumoto and Hikosaka, 2007).