Effects of pharmacological manipulations of NMDA-receptors on deliberation in the Multiple-T task

Abstract

Both humans and non-human animals have the ability to navigate and make decisions within complex environments. This ability is largely dependent upon learning and memory processes, many of which are known to depend on NMDA-sensitive receptors. When humans come to difficult decisions they often pause to deliberate over their choices. Similarly, rats pause at difficult choice points. This behavior, known as vicarious trial and error (VTE), is hippocampally dependent and entails neurophysiological representations of expectations of future outcomes in hippocampus and downstream structures. In order to determine the dependence of VTE behaviors on NMDA-sensitive receptors, we tested rats on a Multiple-T choice task with a reward-delivery reversal known to elicit VTE. Rats under the influence of NMDA-receptor antagonists (CPP) showed a significant reduction in VTE, particularly at the reward reversal, implying a role for NMDA-sensitive receptors in the generation of vicarious trial and error behaviors.

Conflict between place and response navigation strategies: Effects on vicarious trial and error (VTE) behaviors

“…The plus maze paradigm permitted the simultaneous examination of multiple VTE characteristics and expands upon our understanding of VTE behavior during deliberative decision-making. Given that hippocampal manipulations impair VTE (Hu and Amsel 1995;Blumenthal et al 2011), we examined VTE on tasks with and without new hippocampal-dependent learning with the prediction that VTE would be greater during hippocampal-dependent learning. Consistent with this hypothesis, VTE was greater on the task requiring new hippocampal learning (Novel Place Task).…”

“…Hippocampal lesions impaired VTE on a nonspatial discrimination task (Hu and Amsel 1995). Administrations of the NMDA antagonist CPP likewise disrupted VTE behaviors in rats trained on the spatial Multiple-T-Maze (Blumenthal et al 2011).…”

“…VTE was preferentially seen at the highcost choice point on the Multiple-T-Maze task (Johnson and Redish 2007;van der Meer and Redish 2010;Blumenthal et al 2011). VTE was seen at the choice point on a spatial delay discounting task, a task where rats had to choose between a smaller immediate reward and a larger delayed reward (Papale et al 2012).…”

“…Lesion and pharmacological studies suggest a relationship between VTE and performance; manipulations that impair performance also show decreased VTE behavior (Hu and Amsel 1995;Blumenthal et al 2011). Therefore, we examined whether VTE was modulated by performance accuracy.…”

“…Neurophysiological studies support the hypothesis that during VTE an animal is using its "cognitive map" by internally representing potential pathways (Johnson and Redish 2007) and evaluating future outcomes (van der Meer and Redish 2010). Various studies have shown that VTE is supported by the hippocampus (Hu and Amsel 1995;Voss et al 2011), occurs early in learning (Tolman 1939;van der Meer and Redish 2010), and increases with changes in task demands (Blumenthal et al 2011). However, to date, it has been difficult to determine the degree to which VTE behavior is linked to the different decisionmaking systems available.…”