Pedunculopontine tegmental nucleus lesions impair probabilistic reversal learning by reducing sensitivity to positive reward feedback

Abstract

Recent findings indicate that pedunculopontine tegmental nucleus (PPTg) neurons encode reward-related information that is context-dependent. This information is critical for behavioral flexibility when reward outcomes change signaling a shift in response patterns should occur. The present experiment investigated whether NMDA lesions of the PPTg affects the acquisition and/or reversal learning of a spatial discrimination using probabilistic reinforcement. Male Long-Evans rats received a bilateral infusion of NMDA (30 nmoles/side) or saline into the PPTg. Subsequently, rats were tested in a spatial discrimination test using a probabilistic learning procedure. One spatial location was rewarded with an 80% probability and the other spatial location rewarded with a 20% probability. After reaching acquisition criterion of 10 consecutive correct trials, the spatial location – reward contingencies were reversed in the following test session. Bilateral and unilateral PPTg-lesioned rats acquired the spatial discrimination test comparable to that as sham controls. In contrast, bilateral PPTg lesions, but not unilateral PPTg lesions, impaired reversal learning. The reversal learning deficit occurred because of increased regressions to the previously ‘correct’ spatial location after initially selecting the new, ‘correct’ choice. PPTg lesions also reduced the frequency of win-stay behavior early in the reversal learning session, but did not modify the frequency of lose-shift behavior during reversal learning. The present results suggest that the PPTg contributes to behavioral flexibility under conditions in which outcomes are uncertain, e.g. probabilistic reinforcement, by facilitating sensitivity to positive reward outcomes that allows the reliable execution of a new choice pattern.

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

“…However, past studies have shown that a rat which has prior exposure to a working memory test or a different maze environment does not affect pharmacological or brain manipulations on behavioral flexibility tests compared to rats who have not had exposure to a working memory test or a different maze environment (DeCoteau & Kesner, 2000; Gilbert et al, 2001; Ragozzino et al, 1998, 1999, 2002). Similarly, acquisition performance in rats from the current study was comparable to that of rats that had not been previously exposed to a spontaneous alternation test (Brown et al, 2012; Syed et al, 2016). Thus, it is unlikely that exploring a maze in a different context influences subsequent spatial discrimination testing.…”

Cholinergic midbrain afferents modulate striatal circuits and shape encoding of action strategies

“…In line with our findings, the role of the PPN in adaptive behavior and action control has been previously addressed by a series of experiments using lesions or pharmacological manipulations. For example, non-specific PPN lesions impair adaptation to incremental walking speeds in a motor task 67 , affect the assimilation of new strategies with a consequent increase in perseverant responses 36,68 , and decrease the sensitivity to reward omissions 69 , thus denoting a failure in adjusting the behavioral state. Furthermore, pharmacological inhibition of the PPN produces a decrease in the responsiveness to degradation in contingencies between action and outcome, but did not change it if contingencies remain unchanged 70 , in line with findings showing impaired ability of rats to adapt to new strategies when the contingencies changed following inhibition of cholinergic transmission in the striatum 4,71 or CINs lesions 72 .…”

Cholinergic Midbrain Afferents Modulate Striatal Circuits and Shape Encoding of Action Control

“…In line with our findings, the role of the PPN in adaptive behavior and action control has been previously addressed by a series of experiments using lesions or pharmacological manipulations. For example, non-specific PPN lesions impair adaptation to incremental walking speeds in a motor task 64 , affect assimilation of new strategies with a consequent increase in perseverant responses 65,66 , and decrease the sensitivity to reward omissions 67 , thus denoting a failure in adjusting the behavioral state. Furthermore, pharmacological inhibition of the PPN produces a decrease in the responsiveness to degradation in contingencies between action and outcome, but did not change it if contingencies remain unchanged 68 , in line with findings showing impaired ability of rats to adapt to new strategies when the contingencies changed following inhibition of cholinergic transmission in the striatum 6,69 or CINs lesions 70 .…”