Long-term synaptic plasticity is a possible mechanism for storing information in the cortical matrix. Stimulus repetition is a basic component of synaptic information storage. Nonetheless, the capability to remember stimuli which appeared consciously only a limited number of times, indicates that stimulus repetition is only one factor among many, which determines memory. Attention and the expectation of reward are other factors contributing to the storage of information in a repetition-independent manner. Most commonly, the two mental states are not totally independent, since attention is often caused by the expectation of a reward. Attention and reward are correlated with the roles of the cholinergic and dopaminergic function in the cortex. Long-lasting dysfunction of the cholinergic or of the dopaminergic systems often result in devastating neurological disorders such as Alzheimer's disease and schizophrenia. These two neurotransmitters trigger intracellular cascades with possible cross-talk points. We hypothesize that the sequential activation of the cholinergic and of the dopaminergic systems triggers a series of molecular events that lowers the cellular threshold for synaptic storage. The focus of our study is the auditory cortex, which hosts a variety of dopamine and acetylcholine Muscatine receptor and is grossly affected by dysfunctions of cholinergic and dopaminergic systems. Our hypothesis is that cortical plasticity is induced by a two-step process initiated by the suppressive effect of acetylcholine on cortico-cortical transmission followed by an increase in synaptic plasticity due to the simultaneous activation of muscarinic and dopaminergic receptors. Our long-term goal is to determine cellular and molecular effects and interactions of acetylcholine and dopamine in the auditory cortex.
Our specific aims are to determine how acetylcholine and dopamine modulate glutamatergic and GABAergic synaptic activity and how their interactions modulate or induce long-term plasticity in the auditory cortex.
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