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

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.

[1]  P. Winn,et al.  Outflow from the nucleus accumbens to the pedunculopontine tegmental nucleus: A dissociation between locomotor activity and the acquisition of responding for conditioned reinforcement stimulated by d-amphetamine , 1994, Neuroscience.

[2]  W. Schultz,et al.  The activity of pars compacta neurons of the monkey substantia nigra is depressed by apomorphine , 1984, Neuroscience Letters.

[3]  R. Spencer,et al.  A cholinergic projection to the rat substantia nigra from the pedunculopontine tegmental nucleus , 1987, Brain Research.

[4]  W. Schultz,et al.  Dopamine responses comply with basic assumptions of formal learning theory , 2001, Nature.

[5]  Pedunculopontine tegmental nucleus lesions impair stimulus--reward learning in autoshaping and conditioned reinforcement paradigms. , 2000, Behavioral neuroscience.

[6]  W. Schultz,et al.  Responses of monkey dopamine neurons during learning of behavioral reactions. , 1992, Journal of neurophysiology.

[7]  Anthony G. Phillips,et al.  Dopamine functions in appetitive and defensive behaviours , 1992, Progress in Neurobiology.

[8]  W. Schultz,et al.  Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions. , 1990, Journal of neurophysiology.

[9]  E. Scarnati,et al.  Pedunculopontine-evoked excitation of substantia nigra neurons in the rat , 1984, Brain Research.

[10]  E. Scarnati,et al.  The function of the pedunculopontine nucleus in the preparation and execution of an externally-cued bar pressing task in the rat , 1999, Behavioural Brain Research.

[11]  C. Blaha,et al.  Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat , 2003, The European journal of neuroscience.

[12]  J. Bolam,et al.  Cholinergic input to dopaminergic neurons in the substantia nigra: A double immunocytochemical study , 1991, Neuroscience.

[13]  D. van der Kooy,et al.  The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  Donald J Woodward,et al.  Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats , 1999, Brain Research.

[15]  D. van der Kooy,et al.  Excitotoxic lesions of the tegmental pedunculopontine nucleus impair copulation in naive male rats and block the rewarding effects of copulation in experienced male rats , 2003, The European journal of neuroscience.

[16]  J. Tepper,et al.  Electrophysiological Pharmacology of Mesencephalic Dopaminergic Neurons , 2002 .

[17]  W. Schultz,et al.  Dopamine neurons of the monkey midbrain: contingencies of responses to active touch during self-initiated arm movements. , 1990, Journal of neurophysiology.

[18]  Arjun Sahgal,et al.  The pedunculopontine tegmental nucleus: a role in cognitive processes? , 1994, Brain Research Reviews.

[19]  G. Krauthamer,et al.  Somatosensory input and thalamic projection of pedunculopontine tegmental neurons , 1992, Neuroreport.

[20]  P. Overton,et al.  Burst firing in midbrain dopaminergic neurons , 1997, Brain Research Reviews.

[21]  B. Hyland,et al.  Firing modes of midbrain dopamine cells in the freely moving rat , 2002, Neuroscience.

[22]  A. Grace,et al.  Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission , 2003, Nature Neuroscience.

[23]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[24]  Mark G. Perkins,et al.  Lesions of pontomesencephalic cholinergic nuclei do not substantially disrupt the reward value of medial forebrain bundle stimulation , 1998, Brain Research.

[25]  W. Schultz,et al.  Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli , 1996, Nature.

[26]  A. Sahgal,et al.  Lesions of the pedunculopontine tegmental nucleus do not alter delayed non-matching to position accuracy , 1994, Behavioural Brain Research.

[27]  H. Condé,et al.  The role of the pedunculopontine tegmental nucleus in relation to conditioned motor performance in the cat I. Context-dependent and reinforcement-related single unit activity , 1998, Experimental Brain Research.

[28]  P. Overton,et al.  Stimulation of the pedunculopontine tegmental nucleus in the rat produces burst firing in A9 dopaminergic neurons , 1999, Neuroscience.

[29]  R. Roth,et al.  Comparison of effects of L-dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones. , 1973, Nature: New biology.

[30]  W. Schultz,et al.  Discrete Coding of Reward Probability and Uncertainty by Dopamine Neurons , 2003, Science.

[31]  B. Bunney,et al.  Dopamine “Autoreceptors”: Pharmacological characterization by microiontophoretic single cell recording studies , 1977, Naunyn-Schmiedeberg's Archives of Pharmacology.

[32]  Peter Redgrave,et al.  A direct projection from superior colliculus to substantia nigra for detecting salient visual events , 2003, Nature Neuroscience.

[33]  T. Robbins,et al.  Pedunculopontine tegmental nucleus lesions impair stimulus--reward learning in autoshaping and conditioned reinforcement paradigms. , 2000, Behavioral neuroscience.

[34]  M. N. Wallace,et al.  Origin of high acetylcholinesterase activity in the mouse superior colliculus , 2004, Experimental Brain Research.

[35]  R. Wise Brain Reward Circuitry Insights from Unsensed Incentives , 2002, Neuron.

[36]  Trevor W Robbins,et al.  Selective deficits in attentional performance on the 5-choice serial reaction time task following pedunculopontine tegmental nucleus lesions , 2001, Behavioural Brain Research.

[37]  E. Garcia-Rill,et al.  Auditory input to the pedunculopontine nucleus: II. Unit responses , 1995, Brain Research Bulletin.

[38]  Joshua W. Brown,et al.  How the Basal Ganglia Use Parallel Excitatory and Inhibitory Learning Pathways to Selectively Respond to Unexpected Rewarding Cues , 1999, The Journal of Neuroscience.

[39]  S. Walker,et al.  An examination of the effects of bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on responding to sucrose reward , 2002, Behavioural Brain Research.

[40]  P. Bickford,et al.  Auditory sensory gating in the rat hippocampus: modulation by brainstem activity , 1993, Brain Research.

[41]  A. Grace,et al.  Nigral dopamine neurons: intracellular recording and identification with L-dopa injection and histofluorescence. , 1980, Science.

[42]  W. Schultz Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey. , 1986, Journal of neurophysiology.

[43]  N. O. Timofeeva,et al.  Activity of Neurons in the Pedunculopontine Nucleus during a Food-Related Operant Conditioned Reflex , 2003, Neuroscience and Behavioral Physiology.

[44]  A. Grace,et al.  Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—1. Identification and characterization , 1983, Neuroscience.

[45]  J. D. Miller,et al.  Mesencephalic dopaminergic unit activity in the behaviorally conditioned rat. , 1981, Life sciences.

[46]  S. T. Kitai,et al.  Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta , 1995, Neuroscience Research.