Pedunculopontine Tegmental Nucleus Controls Conditioned Responses of Midbrain Dopamine Neurons in Behaving Rats

Abstract

Midbrain dopamine (DA) neurons respond to sensory cues that predict reward. We tested the hypothesis that projections from the pedunculopontine tegmental nucleus (PPTg) are involved in driving this DA cell activity. First, the activity of PPTg and DA neurons was compared in a cued-reward associative learning paradigm. The majority of PPTg neurons showed phasic responses to the onset of sensory cues, at significantly shorter latency than DA cells, consistent with a PPTg-to-DA transmission of information. However, unlike DA cells, PPTg responses were almost entirely independent of whether signals were associated with rewards. Second, DA neuron responses to the cues were recorded in free-moving rats during reversible inactivation of the PPTg by microinfusion of local anesthetic. The results showed clear suppression of conditioned sensory responses of DA neurons after PPTg inactivation that was not seen after saline infusion or in non-DA cells. We propose that the PPTg relays information about the precise timing of attended sensory events, which is integrated with information about reward context by DA neurons.

Reward Prediction Error Computation in the Pedunculopontine Tegmental Nucleus Neurons

“…There have been only a few studies examining visual responses of PPTN neurons. Pan & Hyland (2005), reported visual responses of PPTN neurons in rats, which had a mean response latency to the onset of a light stimulus of 70 ms, but they observed no variable visual responses for reward prediction (Pan & Hyland, 2005). In contrast to these results, a population of our recorded PPTN neurons in primates responded differentially to a visual stimulus with dependent on motivational state.…”

“…The prolonged response of the fixation target neurons indicates that they may maintain the signals of the predicted reward from the time of cue presentation until the reward delivery neurons signal the actual reward magnitude. This study revealed that the strong excitatory inputs exerted by the PPTN on midbrain dopamine neurons (Mena-Segovia et al, 2004;Pan & Hyland, 2005;Winn, 2006) convey the memory of the predicted reward and the signals of the actual reward, two essential elements needed for computing the reward prediction error. The high information capacities of the fixation target and reward delivery neurons to signal the reward magnitude may help the dopamine neurons to accurately compute the reward prediction error and to efficiently execute reinforcement learning.…”

“…A number of studies have found impairments in learning following excitotoxic lesions of the PPTN (Fujimoto et al, 1989;Fujimoto et al, 1992;Steckler et al, 1994;Inglis et al, 2000;Alderson et al, 2002). Thus, abundant anatomical, electrophysiological and pharmacological studies of slice and whole animal preparations indicate that the PPTN receives signals from the reward related structures including the cerebral cortices and the striatum (Winn et al, 1997) and provides strong excitatory inputs to the dopamine neurons (Clements & Grant, 1990;Blaha & Winn, 1993;Futami et al, 1995;Oakman et al, 1995;Blaha et al, 1996;Conde et al, 1998;Dormont et al, 1998;MenaSegovia et al, 2004;Pan & Hyland, 2005;Mena-Segovia et al, 2008). Interestingly, the dopamine/ acethylcholine interaction seems to be mutual (Scarnati et al, 1987); dopmine neurons in the substantia nigra pars compacta tproject back to PPTN neurons, affecting their excitability.…”

The Hippocampus Modulates Dopamine Neuron Responsivity by Regulating the Intensity of Phasic Neuron Activation

“…Schultz and others have shown that presentation of reward-related signals induces transient burst firing in DA neurons only when the reward-related signal is unpredicted (ie novel) (Schultz, 1998). Furthermore, the PPTg has been shown to respond to sensory stimuli (Grunwerg et al, 1992;Reese et al, 1995) and it has been suggested that this region may be involved in signal detection independent of its behavioral salience (Pan and Hyland, 2005); therefore, the PPTg may be involved in detecting a signal with the hippocampus evaluating its novelty (Lisman and Grace, 2005). Since the computation of novelty requires the comparison of incoming information with stored memories, this likely occurs in the hippocampus (Knight, 1996).…”

“…Thus, vSub activation excites Acb projection neurons that inhibit ventral pallidal GABAergic afferents to the VTA, thereby releasing DA neurons from a tonic inhibitory influence (Floresco et al, 2001). In contrast, the pedunculopontine tegmental nucleus (PPTg) is a glutamatergic/cholinergic region driven by a number of limbic afferents, including the prefrontal cortex, bed nucleus of the stria terminalis and central nucleus of the amygdala (Semba and Fibiger, 1992), and has been shown to be activated by auditory (Pan and Hyland, 2005;Reese et al, 1995), visual (Pan and Hyland, 2005) and somatosensory stimuli (Grunwerg et al, 1992). The PPTg was found to also directly regulate burst firing of DAergic neurons (Floresco et al, 2001;Lokwan et al, 1999).…”