This review presents the hypothesis that the best way to consider the pedunculopontine tegmental nucleus is by analogy with the substantia nigra. The substantia nigra contains two main compartments: ...the pars compacta and the pars reticulata. The former contains dopamine neurons that project widely within the basal ganglia while the latter is in receipt of corticostriatal output. Similarly, the PPTg contains the Ch5 acetylcholine containing neurons that project to the thalamus and corticostriatal systems (notably the pars compacta of substantia nigra and the subthalamic nucleus) while the non-cholinergic neurons of the pedunculopontine are in receipt of corticostriatal output. Assessment of the location, composition and connections of the pedunculopontine tegmental nucleus is made to support the hypothesis that it has structural similarities with substantia nigra. Assessment of the motor, sensory and cognitive functions of the pedunculopontine is also made, suggesting functional similarities exist also. Having a clear model of pedunculopontine structure and function is a matter of some importance. It is clearly involved in Parkinson's disease and could potentially be a target for therapeutic intervention. If this is to be realized it will be best to have as clear an understanding as possible of pedunculopontine structure and function in order to maximize positive benefits.
The pedunculopontine tegmental nucleus (PPTg) has been proposed as a target for deep brain stimulation (DBS) in parkinsonian patients, particularly for symptoms such as gait and postural difficulties ...refractory to dopaminergic treatments. Several patients have had electrodes implanted aimed at the PPTg, but outcomes have been disappointing, with little evidence that gait and posture are improved. The PPTg is a heterogeneous structure. Consequently, exact target sites in PPTg, possible DBS mechanisms, and potential benefits still need systematic investigation in good animal models. We have investigated the role of PPTg in gait, developed a refined model of parkinsonism including partial loss of the PPTg with bilateral destruction of nigrostriatal dopamine neurons that mimics human pathophysiology, and investigated the effect of DBS at different PPTg locations on gait and posture using a wireless device that lets rats move freely while receiving stimulation. Neither partial nor complete lesions of PPTg caused gait deficits, underlining questions raised previously about the status of PPTg as a motor control structure. The effect of DBS in the refined and standard model of parkinsonism were very different despite minimal behavioral differences in nonstimulation control conditions. Anterior PPTg DBS caused severe episodes of freezing and worsened gait, whereas specific gait parameters were mildly improved by stimulation of posterior PPTg. These results emphasize the critical importance of intra-PPTg DBS location and highlight the need to take PPTg degeneration into consideration when modeling parkinsonian symptoms. They also further implicate a role for PPTg in the pathophysiology of parkinsonism.
► We tested the role of D2 receptors in active avoidance conditioning. ► Fast learning required activation of D2 receptors in the nucleus accumbens. ► Slower learning required activation of D2 ...receptors in the dorsolateral striatum.
The role of dopamine (DA) in rewarding motivated actions is well established but its role in learning how to avoid aversive events is still controversial. Here we tested the role of D2-like DA receptors in the nucleus accumbens (NAc) and the dorsolateral striatum (DLS) of rats in the learning and performance of conditioned avoidance responses (CAR). Adult male Wistar rats received systemic, intra-NAc or intra-DLS (pre- or post-training) administration of a D2-like receptor agonist (quinpirole) or antagonist ((−)sulpiride) and were given two sessions in the two-way active avoidance task. The main effects observed were: (i) sulpiride and lower (likely pre-synaptic) doses of quinpirole decreased the number of CARs and increased the number of escape failures; (ii) higher doses of quinpirole (likely post-synaptic) increased inter-trial crossings and failures; (iii) pre-training administration of sulpiride decreased the number of CARs in both training and test sessions when infused into the NAc, but this effect was observed only in the test session when it was infused into the DLS; (iv) post-training administration of sulpiride decreased CARs in the test session when infused into the NAc but not DLS. These findings suggest that activation of D2 receptors in the NAc is critical for fast adaptation to responding to unconditioned and conditioned aversive stimuli while activation of these receptors in the DLS is needed for a slower learning of how to respond to the same stimuli based on previous experiences.
•The pedunculopontine tegmental nucleus is essential for action–outcome learning.•Sensitivity to instrumental contingency degradation is blocked by PPTg inactivation.•Inactivation of PPTg does not ...change performance of previously learnt operant tasks.•This is the first demonstration of a role for brainstem in action–outcome learning.•Learning functions of basal ganglia extend into the deepest parts of the circuitry.
The pedunculopontine tegmental nucleus (PPTg) is in a pivotal position between the basal ganglia and brainstem: it is able to influence and regulate all levels of basal ganglia and corticostriatal activity as well as being a key component of brainstem reticular and motor control circuitry. Consistent with its anatomical position, the PPTg has previously been shown to process rapid, salient sensory input, is a target for Parkinson’s disease treatments and has been implicated in associative learning. We explicitly investigated the role of the posterior pPPTg (pPPTg) in action–outcome processes, where actions are performed with the goal-directed aim of obtaining an anticipated outcome. We assessed rats’ sensitivity to degradation of the contingency between actions (lever pressing) and outcomes (food reward) during either inactivation of pPPTg by microinjection of the GABA agonist muscimol or control infusions of saline. In response to the degradation of contingency between lever press and food reward, saline treated rats rapidly reduced rates of lever pressing whereas muscimol treated rats (pPPTg inactivation) maintained previous lever pressing rates. In contrast, when the contingency between lever press and food reward was unchanged saline and muscimol treated rats maintained their previous rates of lever pressing. This shows that the pPPTg is critically required for updating associations between actions and outcomes, but not in the continued performance of previously learned associations. These results are consistent with a role for the PPTg in ‘higher-order’ associative learning and are the first to demonstrate a brainstem role in action–outcome learning.
Rationale
Aversively motivated learning is more poorly understood than appetitively motivated learning in many aspects, including the role of dopamine receptors in different regions of the striatum.
...Objectives
The present study investigated the roles of the D1-like DA receptors in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) on learning and performance of conditioned avoidance responses (CARs).
Methods
Adult male Wistar rats received intraperitoneal (i.p.), intra-NAc, or intra-DLS injections of the D1 dopamine receptor agonist SKF 81297 or the D1 receptor antagonist SCH 23390 20 min before or immediately after a training session in the CAR task two-way active avoidance, carried out 24 h before a test session.
Results
Pre-training administration of SCH 23390, but not SKF 81297, caused a significant decrease in the number of CARs in the test, but not in the training session, when injected into the DLS, or in either session when injected into the NAc. It also caused a significant increase in the number of escape failures in the training session when injected into the NAc. Systemic administration caused a combination of these effects. Post-training administrations of these drugs caused no significant effect.
Conclusions
The results suggest that the D1-like receptors in the NAc and DLS play important, though different, roles in learning and performance of CAR.
The pedunculopontine tegmental nucleus (PPTg) is in a key position to participate in operant reinforcement via its connections with the corticostriatal architecture and the medial reticular ...formation. Indeed, previous work has demonstrated that rats bearing lesions of the whole PPTg are impaired when learning to make two bar presses for amphetamine reinforcement. Anterior and posterior portions of the PPTg make different anatomical connections, including preferential projections by the anterior PPTg to substantia nigra pars compacta dopamine neurons and by the posterior PPTg to ventral tegmental area dopamine neurons. We wanted to assess the effects of anterior and posterior PPTg ibotenate lesions on rats learning simple and more complex schedules of natural reinforcement. We trained rats with lesions to the anterior PPTg (n = 11) and the posterior PPTg (n = 5) and appropriate controls (n = 15) to bar press for food on a variety of fixed‐ratio and variable‐ratio reinforcement schedules and then during extinction. We found that posterior PPTg‐lesioned rats bar pressed at lower rates, were slower to learn to bar press, and often had deficits characteristic of impaired learning and/or motivation. In contrast, anterior PPTg‐lesioned rats learned to bar press for reinforcement at normal rates. However, they made errors of perseveration and anticipation throughout many schedules, and pressed at a higher rate than controls during extinction, deficits best characterized as reflecting disorganized response control. Together, these data suggest that the anterior PPTg and posterior PPTg (and their related circuits) contribute differently to reinforcement learning, incentive motivation, and response control, processes that are considered to malfunction in drug addiction.
Abstract The pedunculopontine tegmental nucleus (PPTg) is involved in Parkinson's disease and has become a therapeutic target. However, its normal functions are uncertain: are they motor, sensory or ...integrative? This position paper reviews PPTg structure and considers experiments designed to understand its behavioural functions. The PPTg is part of the corticostriatal architecture and, consistent with this, a core deficit following lesion is the inability to properly establish action–outcome associations. Understanding normal PPTg structure and function will provide insight into the role it has in Parkinson's disease and related disorders, and will benefit the development of surgical treatments aimed here.
In this review, it is argued that the consequence of bilateral damage to the pedunculopontine tegmental nucleus (PPTg) in experimental animals is the production of a form of frontal syndrome. Frontal ...syndrome is a term used to describe the behavioural consequences of damage to the frontal lobes in human patients. These behavioural changes can be classified as disinhibition of behaviour (a release of behavioural control), the production of inappropriate behaviour (which in patients can be either inappropriate actions or verbal behaviour), and the production of perseverative behaviour (the maintenance of an action beyond the point at which it should have been terminated). The psychological changes which underlie these behavioural changes are thought to involve executive functions, which include such things as the prospective planning of sequences of actions, attentional shifting and working memory. In this review, I attempt to demonstrate two things: first, that there are significant anatomical connections from frontostriatal systems to the PPTg. The motor cortex projects directly to the PPTg while the prefrontal cortex contacts it via striatal circuitry, forming clear routes by which the frontal lobes can communicate with the PPTg. Second, having established the existence of connections between frontostriatal systems and the PPTg, behavioural data are described. Experimental animals bearing bilateral lesions of the PPTg have been examined in a wide variety of tasks. Animals bearing such lesions are not impaired in basic processes of feeding, drinking, locomotion, or grooming and simple observation of lesioned rats’ normal behaviour reveals no obvious gross impairment in function. However, the results of more subtle tests reveal a wide variety of deficits in various tasks. The outcome of these experiments are in many ways contradictory, but in the vast majority of cases, the changes can be described as involving disinhibition of behaviour, the release of inappropriate behaviour, and the production of perseverative behaviour. Anatomical and behavioural data support the conclusion that there are functional connections between frontal systems and the PPTg. This review also discusses what psychological processes might be served by such connections.
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