The overall objective of this research project is to elucidate the roles of specific basal forebrain (BF) neuronal populations as potential neural mechanisms for attention. During the current reporting period, our major research effort was to determine how BF inputs may shape the attention-related activity in the prefrontal cortex. We have adopted the commonly used oddball procedure in human attention studies in the rat. Rats were presented with a stream of frequent standard tones and infrequent target tones once every two seconds. Response to the target, but not to the standard, resulted in reward delivery. The same rats were also trained in an analogous oddball task with two distinct visual cues. We found that BF neurons respond to the onset of the target with robust bursting of spikes, while the bursting strength to the standard was much weaker and variable across trials. In the prefrontal cortex, we identified a layer-specific event-related potential (ERP) response in the local field potential (LFP) activity. This ERP response was tightly correlated with the BF response in single trials, both in terms of amplitude and timing. This observed correlation between BF and PFC ERP responses were similarly present in both auditory and visual oddball tasks, therefore was independent of sensory modality. To determine if the observed correlation was causal, i.e. whether the PFC ERP response was generated by the BF bursting activity, we electrically stimulated the BF and observed a similar ERP response in the PFC, thus supporting a causal role of the BF. Overall, these data suggest that a component of attention-related ERP in the PFC can be generated by a subcortical input via the bursting of non-cholinergic BF neurons. Through this mechanism, the BF can translate the motivational salience signal encoded by the bursting response into fast modulation of cortical neuronal excitability. Future experiments seek to characterize the nature of neurotransmitter involved in generating the ERP response. In a separate collaborative study with Dr. Hao Zhang and Dr. Miguel Nicolelis at Duke University, we investigated how neurons in the rostral BF complex, the medial septum - vertical limb of the diagonal band of Broca (MSvDB), may modulate the theta oscillation activity in the hippocampus. While many previous studies have focused on understanding how MSvDB neurons fire rhythmic bursts to pace hippocampal theta oscillations, a significant portion of MSvDB neurons are slow-firing and thus do not pace theta oscillations. The function of these MSvDB neurons, especially their role in modulating hippocampal activity, remains unknown. We recorded MSvDB neuronal ensembles in behaving rats, and identified a distinct, physiologically homogeneous subpopulation of slow-firing neurons (overall firing <4Hz) which shared three features: 1) much higher firing rate during rapid-eye-movement (REM) sleep than during slow-wave (SW) sleep;2) temporary activation associated with transient arousals during SW sleep;3) brief responses (15-30 ms latency) to auditory stimuli. Analysis of the fine temporal relationship of their spiking and theta oscillations showed that unlike the theta-pacing neurons, the firing of these pro-arousal neurons follows theta oscillations. However, their activity precedes short-term increases in hippocampal oscillation power in the theta and gamma range lasting for a few seconds. Together, these results suggest that these pro-arousal slow-firing MSvDB neurons may function collectively to promote hippocampal activation.
