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. Specifically, we seek to determine how attention-related cortical activity is dynamically shaped by BF inputs. Substantial effort during the current reporting period has focused predominantly on start-up activities, including lab set up, staff recruitment and training, animal acquisition and the development of behavioral paradigms. As a first step toward establishing rodent behavioral tasks that capture behavioral and electrophysiological signatures of attention tasks used in human studies, 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 (90%, 10kHz) and infrequent target tones (10%, 6kHz) once every second. Response to the target, but not to the standard, results in reward delivery. We are characterizing the neurophysiological responses in order to validate this paradigm as a model of human ERP responses. In a separate collaborative study with Dr. Hao Zhang and Dr. Miguel Nicolelis at Duke University, we investigated the real-time in vivo dynamic interaction between acetylcholine release originating from the medial septum, the anterior extension of the BF, and the neurophysiological activity (theta oscillation) in the hippocampus. By implementing simultaneous amperometric and electrophysiological recordings in urethane-anesthetized rats, we established that the phasic in vivo acetylcholine release is tightly coupled with hippocampal theta oscillation, on spatiotemporal scales (over tens of seconds and within 0.3mm depth) much finer than previously known. Moreover, we found that the phasic acetylecholine signal lagged behind the onset of theta oscillation by 25-60 seconds, suggesting that acetyocholine modulation may not be required for the initiation of theta oscillations. Instead, our findings suggest that acetylcholine signals may be recruited after sustained theta oscillation, to operate synergistically with theta oscillations in order to promote plasticity in the hippocampus.
