The overall objective of this research project is to elucidate the roles of basal forebrain (BF) neurons as potential neural mechanisms for attention. During the current reporting period, our research effort focused on two main questions: (1) how does BF neuronal activity facilitate response speed in the context of top-down attention;and (2) how does BF activity mediate the influence of attention on enhancing cortical neural activity, especially in terms of event-related potential (ERP) responses. Given that aging is associated with reduced processing speed as well as changes in ERP responses, these investigations will help to better understand the neural mechanisms of cognitive aging. Reaction time (RT) provides a quantitative measure of response speed and is widely used as a simple behavioral readout of various cognitive functions, including attention. To understand the functional organization and neural control of fast RT responses, we recorded neuronal activity in the BF while rats performed a reward-guided RT task. Our study showed that, between different RT distributions, the speed and variability of RT distributions are correlated with, and likely controlled by, the ensemble bursting of non-cholinergic BF neurons. Within the same RT distribution, however, the strength of BF bursting was not differentially modulated between fast and slow RT trials. Consistent with a causal relationship, direct activation of the BF via electrical microstimulation resulted in faster RT distributions with predictable shifts in the RT distribution shape compared with non-stimulated controls. Together, these results reveal a novel distribution-level organization of fast RT responses and support that the bursting response of non-cholinergic BF neurons controls the speed of the entire RT distribution, but not the speed of individual trials within the distribution. Therefore, non-cholinergic BF neurons, which encode motivational salience of attended stimuli, likely mediate the influence of attention on facilitating the speed of behavioral response. To further understand whether the influence of attention on enhancing cortical neural activity may be mediated by BF neuronal activity, we studied the relationship between the activity of non-cholinergic BF neurons and attention-related ERP responses in the prefrontal cortex (PFC). ERPs have been widely used as an objective physiological index of attention and other cognitive functions but their underlying neural circuit mechanisms remain unclear. Our study showed that, in rats performing an active oddball task, the first prominent negative N1 ERP component in the frontal cortex is correlated with, and likely caused by, the ensemble bursting activity of non-cholinergic BF neurons. We found that, on a single trial basis, the frontal N1 ERP and BF bursting were tightly coupled in time and in amplitude, across both auditory and visual domains. Furthermore, the frontal N1 ERP showed a characteristic depth profile across the layers of PFC circuits, which was mimicked by BF electrical stimulation. These data support the idea that non-cholinergic BF neurons may gate the generation of an attention-related cortical ERP, thus translating the motivational salience signal into fast modulation of cortical neuronal excitability.
