Bar pressing for food: differential consequences of lesions to the anterior versus posterior pedunculopontine

Abstract

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.

Nicotine self-administered directly into the VTA by rats is weakly reinforcing but has strong reinforcement enhancing properties

“…It is likely that a different process is mediated by VTA mAChRs-possibly one that is more generally activating, given the large and prolonged elevation of DA release. (2) It is also consistent with experiments showing that excitotoxic lesions of posterior PPTg (a source of cholinergic input to VTA) but not anterior PPTg impair learning reinforced by natural rewards or drugs (Alderson et al 2008;Wilson et al 2009;Winn et al 2009). (3) Electrophysiological data in primates show that PPTg neurons respond in a proportionally graded manner either to signals predicting reward or to reward delivery (Okada et al 2009)-two pieces of information critical to forming predictive associations.…”

Location of Infarcts and Apathy in Ischemic Stroke

“…Animal studies have provided an increasingly sophisticated understanding of the processes underlying normal human motivation and its disruption or dysregulation in apathy. PPN lesions block the motivational effects of ethanol [28,29], morphine, amphetamine [30] and reward learning [31] and cause motivational dysfunction [32] in rats. Other pontine regions involved in motivation and reward are the dorsal raphe nuclei [33].…”

Selective lesions of the cholinergic neurons within the posterior pedunculopontine do not alter operant learning or nicotine sensitization

“…Here, we used this toxin to assess specifically the contributions of cholinergic neurons within pPPTg to instrumental learning and the locomotor response to systemic nicotine. In experiment 1, rats were tested in an exact replication of the instrumental learning protocol in which we demonstrated a persistent learning impairment after excitotoxic lesion of pPPTg (Wilson et al 2009). In experiment 2, the rate and extent of locomotor sensitization to repeated systemic nicotine were assessed in a replication of the protocol used by Alderson et al (2008), which found altered sensitization in excitotoxic pPPTg-lesioned rats.…”

“…Excitotoxic lesions restricted to the posterior PPTg (pPPTg) impair the ability to learn foodrewarded instrumental tasks (Wilson et al 2009). Such lesions also alter the locomotor response to repeated systemic nicotine-reducing the initial hypolocomotion and increasing subsequent hyperlocomotion (Alderson et al 2008).…”