Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert

Abstract

Associative learning is crucial for daily function, involving a complex network of brain regions. One region, the nucleus basalis of Meynert (NBM), is a highly interconnected, largely cholinergic structure implicated in multiple aspects of learning. We show that single neurons in the NBM of nonhuman primates (NHPs; = 2 males;) encode learning a new association through spike rate modulation. However, the power of low-frequency local field potential (LFP) oscillations decreases in response to novel, not-yet-learned stimuli but then increase as learning progresses. Both NBM and the dorsolateral prefrontal cortex encode confidence in novel associations by increasing low- and high-frequency LFP power in anticipation of expected rewards. Finally, NBM high-frequency power dynamics are anticorrelated with spike rate modulations. Therefore, novelty, learning, and reward anticipation are separately encoded through differentiable NBM signals. By signaling both the need to learn and confidence in newly acquired associations, NBM may play a key role in coordinating cortical activity throughout the learning process. Degradation of cells in a key brain region, the nucleus basalis of Meynert (NBM), correlates with Alzheimer's disease and Parkinson's disease progression. To better understand the role of this brain structure in learning and memory, we examined neural activity in the NBM in behaving nonhuman primates while they performed a learning and memory task. We found that single neurons in NBM encoded both salience and an early learning, or cognitive state, whereas populations of neurons in the NBM and prefrontal cortex encode learned state and reward anticipation. The NBM may thus encode multiple stages of learning. These multimodal signals might be leveraged in future studies to develop neural stimulation to facilitate different stages of learning and memory.

Forebrain Cholinergic Signaling: Wired and Phasic, Not Tonic, and Causing Behavior

“…We further demonstrated that the behavioral power of cholinergic transients is due to the generation of high-frequency oscillations in cortex that persist beyond the cue period and required muscarinic M1 acetylcholine receptor (mAChR) stimulation (Howe et al, 2017). Thus, fast, phasic and precisely timed presynaptic cholinergic signaling can give rise to relatively long-lasting postsynaptic effects (Hangya et al, 2015;Martinez-Rubio et al, 2018;Urban-Ciecko et al, 2018) (see also Case study 2, below).…”

The amygdala instructs insular feedback for affective learning

“…Basal forebrain cholinergic neurons rapidly respond to reinforcement feedback in both valence domains ( Hangya et al, 2015 ). Since neurons in the CE are unlikely to mediate NBM response to US, we posit that CE neurons and the CE–NBM axis integrate primary reinforcement signals ( Cui et al, 2017 ) with information on novelty, confidence, and expectation ( Martinez-Rubio et al, 2018 ; Steinberg et al, 2020 ), which is relayed to the IC and the amygdala itself ( Yu et al, 2017 ). Indeed, these higher order prediction errors, which incorporate hierarchical probability distributions, have been mapped onto the basal forebrain in humans ( Iglesias et al, 2013 ).…”

Role of Cholinergic Signaling in Alzheimer’s Disease

“…It may have a key function in coordinating cortical activity throughout the learning process, as novelty, learning and reward expectation are encoded by different NBM signals. Its cellular degradation is associated with the progression of AD and Parkinson [ 32 ].…”