Lateral habenula as a source of negative reward signals in dopamine neurons

Abstract

Midbrain dopamine neurons are key components of the brain's reward system, which is thought to guide reward-seeking behaviours. Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward, it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes. Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons.

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Hypotheses about the role of dopamine in reinforcement learning are closely tied to the finding that dopamine neurons fire in relation to (positive) prediction errors in rewarded tasks [119][120][121][122][123][124][125]. Substantia nigra pars compacta neurons also receive information about negative prediction errors, through connections that originate in the lateral habenula [126][127][128][129][130][131].…”

Reward Prediction Error Computation in the Pedunculopontine Tegmental Nucleus Neurons

“…Furthermore GABAergic axon terminals originating from the PPTN were observed in the midbrain (Charara et al, 1996), these inhibitory connections may inhibit dopamine neurons and generate the inhibitory reward omission response. Alternatively, the inhibitory reward signals may be sent to the dopamine neurons from other neuronal structures such as the striosome (Brown et al, 1999;Contreras-Vidal & Schultz, 1999), ventral pallidum (Wu et al, 1996), habenula (Matsumoto & Hikosaka, 2007) and rostromedial tegmental nucleus (Jhou et al, 2009). Finally, we present our hypothesis of how the PPTN drives dopamine neurons to compute the reward prediction error signal (Fig.…”

Effects of Drugs of Abuse on Putative Rostromedial Tegmental Neurons, Inhibitory Afferents to Midbrain Dopamine Cells

“…Aversive stimuli have been reported to induce both excitation (Brischoux et al, 2009) and inhibition (Ungless et al, 2004) of DA neurons, a heterogeneous response correlated to specific subgroups of DA neurons (ventral and dorsal, respectively) within the ventral tegmental area (VTA). On the other hand, glutamatergic neurons in the lateral habenula (LHb), an epithalamic region involved in the mechanisms of fear, anxiety, and stress, respond in a reverse manner, being inhibited by rewards and excited by aversive stimuli (Hikosaka et al, 2008;Matsumoto and Hikosaka, 2007). Noteworthy, activity of DA and LHb neurons appears to be causally correlated, as electrical stimulation of the LHb inhibits DA neurons (Christoph et al, 1986;Ji and Shepard, 2007;Matsumoto and Hikosaka, 2007).…”

“…On the other hand, glutamatergic neurons in the lateral habenula (LHb), an epithalamic region involved in the mechanisms of fear, anxiety, and stress, respond in a reverse manner, being inhibited by rewards and excited by aversive stimuli (Hikosaka et al, 2008;Matsumoto and Hikosaka, 2007). Noteworthy, activity of DA and LHb neurons appears to be causally correlated, as electrical stimulation of the LHb inhibits DA neurons (Christoph et al, 1986;Ji and Shepard, 2007;Matsumoto and Hikosaka, 2007). However, the sparse innervation of DA neurons by excitatory LHb afferents (Brinschwitz et al, 2010;Omelchenko et al, 2009) unlikely explains this inhibition, and the presence of an area intermediate between the LHb and the VTA was originally postulated.…”