Abstract
The basal forebrain, composed of distributed nuclei, including substantia innominata (SI), nucleus basalis and nucleus of the diagonal band of Broca plays a crucial neuromodulatory role in the brain. In particular, its projections to the prefrontal cortex have been shown to be important in a wide variety of brain processes and functions, including attention, learning and memory, arousal, and decision-making. In the present study, we asked whether the basal forebrain is involved in recruitment of cognitive effort in response to reward-related cues. This interaction between motivation and cognition is critically impacted in psychiatric conditions such as schizophrenia. Using the Designer Receptor Exclusively Activated by Designer Drug (DREADD) technique combined with our recently developed signaled probability sustained attention task (SPSA), which explicitly assays the interaction between motivation and attention, we sought to determine the role of the basal forebrain in this interaction. Rats were stereotaxically injected in the basal forebrain with either hM4D(Gi) (a virus that expresses receptors which silence neurons in the presence of the drug clozapine-N-oxide; CNO) or a control virus and tested in the SPSA. Behavior of rats during baseline and under saline indicated control by reward probability. In the presence of CNO, differential accuracy of hM4D(Gi) rats on high and low reward-probability trials was abolished. This result occurred despite spared ability of the reward-probability signals to differentially impact choice-response latencies and omissions. These results indicate that the basal forebrain is critical for the motivational recruitment of attention in response to reward-related cues and are consistent with a role for basal forebrain in encoding and transmitting motivational salience of reward-related cues and readying prefrontal circuits for further attentional processing.
Highlights
Behavioral flexibility refers to the ability to adjust behavior adaptively in response to stimuli or changes in contingency in the environment
In our previous studies we have shown that discrimination accuracy on high reward-probability trials is higher than accuracy on low reward-probability trials, and we have interpreted this as evidence that the reward probability signal acts as a cognitive incentive, leading to increased cognitive effort on high reward-probability trials
We have previously shown that prefrontal cortex and striatum are critical for the ability of reward probability signals to modulate attention in our task (Ward et al, 2015a,b; Hall-McMaster et al, 2017)
Summary
Behavioral flexibility refers to the ability to adjust behavior adaptively in response to stimuli or changes in contingency in the environment. Prefrontal cortical areas have been implicated (Duncan and Owen, 2000; Johnstone et al, 2007) These areas receive a direct projection from the basal forebrain (BF; including substantia innominata (SI), nucleus basalis, nucleus of the diagonal band of Broca and the nucleus basalis of Meynert (Woolf, 1991; Zaborszky, 2002; Zaborszky et al, 2012, 2015). This projection, comprising both cholinergic and GABAergic neurons (and a smaller glutamatergic projection), is one of the more important modulatory circuits in the brain (Gritti et al, 2006). The GABAergic neurons, while relatively less studied than the cholinergic projections, have been shown to modulate cortical networks which are associated with cognition, and are thought to participate in decision-making processes (Sarter and Bruno, 2002; Lin et al, 2006; Zaborszky et al, 2012; Nguyen and Lin, 2014; Anaclet et al, 2015)
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