Basal forebrain motivational salience signal enhances cortical processing and decision speed

Abstract

The basal forebrain (BF) contains major projections to the cerebral cortex, and plays a well-documented role in arousal, attention, decision-making, and in modulating cortical activity. BF neuronal degeneration is an early event in Alzheimer’s disease (AD) and dementias, and occurs in normal cognitive aging. While the BF is best known for its population of cortically projecting cholinergic neurons, the region is anatomically and neurochemically diverse, and also contains prominent populations of non-cholinergic projection neurons. In recent years, increasing attention has been dedicated to these non-cholinergic BF neurons in order to better understand how non-cholinergic BF circuits control cortical processing and behavioral performance. In this review, we focus on a unique population of putative non-cholinergic BF neurons that encodes the motivational salience of stimuli with a robust ensemble bursting response. We review recent studies that describe the specific physiological and functional characteristics of these BF salience-encoding neurons in behaving animals. These studies support the unifying hypothesis whereby BF salience-encoding neurons act as a gain modulation mechanism of the decision-making process to enhance cortical processing of behaviorally relevant stimuli, and thereby facilitate faster and more precise behavioral responses. This function of BF salience-encoding neurons represents a critical component in determining which incoming stimuli warrant an animal’s attention, and is therefore a fundamental and early requirement of behavioral flexibility.

Input dependent modulation of olfactory bulb activity by GABAergic basal forebrain projections

“…By inhibiting weak and facilitating strong inputs, GABAergic BF fibres in the OB likely increase MTCs signal-to-noise ratio, a hallmark of attentional processes that have been previously attributed mainly to cholinergic processes [2][3][4]9,10 . Our findings are in line with recent data indicating that the classical view on the (cholinergic) BF system might be oversimplified: activity of non-cholinergic BF neurons was more strongly correlated with arousal and attention [11][12][13][14][15] , whereas cholinergic neuron activity was correlated with body movements, pupil dilations, licking, punishment 75,103 as well as primary reinforcers and outcome expectations 11 . The distinct early sensory modulation effects of cholinergic and GABAergic BF neurons observed in this study might therefore be owed to the different functions of these two basal forebrain systems.…”

“…Furthermore, they have been identified as key players in mediating attentional modulation of sensory processing as well as in coordinating cognitive operations 9,10 . However, the concept of a prevalent role of cholinergic cells in the BF was recently challenged as activity of non-cholinergic neurons was shown to strongly correlate with arousal and attention [11][12][13][14][15] . Despite the knowledge of BF subpopulations containing neurotransmitters different from acetylcholine [16][17][18][19] no direct comparison of modulation effects caused by cholinergic and non-cholinergic projections is currently available.…”

The menagerie of the basal forebrain: how many (neural) species are there, what do they look like, how do they behave and who talks to whom?

“…Additional markers to identify this subgroup of GABAergic neurons are lacking at present. A subpopulation of slowly-discharging, non-cholinergic BF neurons, possibly GABAergic, which lack strong state-dependent modulation of discharge encode motivational salience [2,52]. …”

Improvement in arm and hand function after a stroke with task-oriented training

“…Treatment sessions were constructed based on fundamental principles of motor learning, for example, intensive,10 task-specific,9 challenging10 and variable training 11 21. Task-specific, challenging training tasks that are context-dependent were reported to enhance motor performance9 by increasing participation and engagement in practice through motivational salience 22. Training tasks were chosen by sharing treatment goals with the patient and his relatives, considering the degree of disability in a specific daily task, to enhance engagement and motivation through the sessions.…”