Investigations of the basal forebrain system have become increasingly more popular over the last two decades. Neuropathology observed in people suffering from Alzheimer's disease (AD) includes degeneration of this region. In addition, damage to this region produces deficits in animal models of learning and memory that parallel the cognitive deficits seen in AD. However, there is still substantial debate concerning the exact nature of these deficits. The majority of investigations into the role of the basal forebrain in learning and memory have used manipulations that reduce basal forebrain function prior to training. Unfortunately, such pre-training manipulations do not differentiate between potential effects on acquisition, consolidation and expression of memories. The set of experiments proposed here are designed to provide a systematic analysis of basal forebrain cholinergic and gamma-aminobutyric acid (GABA)ergic modulation in the acquisition, consolidation and expression of fear conditioning. Using selective pre- and post-training lesions of either cholinergic or GABA-ergic neurons in the basal forebrain, current competing hypotheses regarding basal forebrain modulation will be tested, such as its proposed roles in attention, encoding and retrieval. Such a complete analysis within a single behavioral paradigm will provide critical insight into the neuropharmacological and anatomical substrates that modulate learning and the formation of long-term memories.
