Functional circuitry of basal forebrain underlying enhanced attention by reward anticipation in rats

Abstract

This thesis focused on the role of the basal forebrain (BF) in the interaction of motivation and attention in Long-Evans rats. The interaction between motivation and attention is critically impacted in psychiatric conditions such as schizophrenia. The neurobiology of both motivation and cognition have long been topics of research interest, however, the specific functional neurocircuitry by which motivation impacts cognition has not been widely studied and remains a matter of debate. This work has indicated areas that are important in this interaction. Accordingly, understanding the neuronal circuitry involved in this interaction is critical to understand functional differences in normal brain and psychiatric disorders. With this aim, we sought to determine whether the basal forebrain is required for the recruitment of cognitive effort in response to reward-related-cues as well as evaluate the nature of any interactions between the BF and the prelimbic cortex (PrL) during reward-modulated attention. To determine the role of the BF in interaction of motivation and attention, in the first experiment, we used the Designer-Receptor-Exclusively-Activated-by-Designer-Drug (DREADD) technique, combined with our recently developed signalled probability sustained attention task, which explicitly evaluates the interaction between motivation and attention. The key finding was that inhibition of BF neuronal activity abolished the ability of reward-related cues to differentially modulate discrimination accuracy. Moreover, BF inhibition did not affect overall attention, as only accuracy on high reward probability trials was impacted. BF inhibition also did not affect perseverative responding, choice-response latency, or omissions, indicating that rats were still able to appreciate the significance of the reward probability signals but were not able to translate this information into adaptive performance. To evaluate the specific contribution/communication between BF and PrL, electrodes were stereotaxically implanted in the target regions and then local field potential (LFP) neural activity of implanted areas were monitored and recorded during the task. We found that unlike the PrL LFPs, for BF LFPs, the difference between high and low probability trials was significant. Also, the discrimination between high and low probability in beta PrL–BF coherence increased significantly across days, which indicated that PrL and BF communication was enhanced across increased experience with the task. Next, we used partial directed coherence (PDC) to determine the directionality of the functional communication between BF and PrL during SPSA performance. The results showed that the influence of SPSA task on the Lead A (PrL → BF) and Lead B (BF → PrL) beta PDC interaction of day × probability was significant. Moreover, the significant discrimination between high and low probability only occurred in Lead B beta PDC, and it was greater than the Lead A beta PDC on the last day. Also, the SPSA task demands across days have a high impact on Lead B beta PDC but not on Lead A. In general, these experiments found that BF is critical for the motivational recruitment of attention in response to reward-related-cues. The BF and the PrL functional connectivity was increased during periods of increased motivational recruitment of attentional resources. Similarly, the BF activity dynamically modulates SPSA performance by recruiting greater PrL attentional resources on high reward-probability trials. These results shed further light on the role of the BF in behavioural flexibility. They also provide further evidence that, contrary to the traditionally-held view of BF as a diffuse and slow modulator of different arousal states, BF activity is involved in the dynamic modulation of cognitive processing in response to behaviourally relevant and motivationally salient environmental cues.