Reward-related learning guides a vast array of adaptive and maladaptive behaviors. The overall goals of this project are to analyze the mechanisms underlying two forms of reward-related learning, appetitive classical and reward operant conditioning. Results from the previous and present project periods demonstrate that similarities exist between classical and operant conditioning at the systems level, but at the cellular level the mechanisms mediating these two forms of learning are fundamentally different. The goals of the present project are to extend this analysis to the molecular level and to other circuit elements.
The Specific Aims are: 1. Investigate the subcellular mechanisms of operant reward learning. Previously an in vitro analogue of operant conditioning was reduced to a single identified neuron (B51) in culture. This analogue procedure induces changes in B51 that are identical to those induced by operant conditioning.
Aim 1 will: 1.1) Characterize the modulation of membrane currents by contingent reinforcement;1.2) Investigate intracellular signaling cascades that mediate the convergence of the operant (neuronal activity) and the reinforcement (dopamine);and 1.3) Examine the role of cAMP response element binding protein 1 (CREB1) in long-term changes in the membrane properties of B51. 2. Characterize the signaling cascades in B51 that underlie short- and long-term appetitive classical conditioning. B51 is a locus of plasticity common to operant and classical conditioning. However, the two forms of learning have very different effects on B51. Operant conditioning increases the excitability of B51, whereas classical conditioning decreases its excitability. To investigate how these two different outcomes emerge, Aim 2 will: 2.1) Investigate the signaling cascades that mediate short-term classical conditioning;and 2.2) Examine the molecular mechanisms of long-term classical conditioning. 3. Identify and analyze additional sites of plasticity following the in vitro analogues of operant and classical conditioning. Although several sites of plasticity have been identified following operant and classical conditioning, other sites, yet to be identified, are necessary to explain all of the changes in behavior following conditioning.
Aim 3 will: 3.1) Determine the extent to which operant conditioning modifies pattern-initiating neurons in the buccal ganglia (e.g., B31/32, B35, B50, B63) and the extent to which classical conditioning modifies command neurons in the cerebral ganglion (e.g., CBI-2 and CBI-3);3.2) Examine the extent to which the signaling cascades that underlie plasticity in B51 generalize to additional sites of plasticity in the pattern-initiating neurons;and 3.3) Determine whether newly identified sites of plasticity in pattern-initiating neurons following the in vitro analogue of operant conditioning are also modified by the in vitro analogue of classical conditioning. The proposed studies will provide a deeper understanding of reward-related learning and may provide insights into related disorders such as addiction, AD/HD, impulsivity and eating disorders.
Reward-related learning guides a vast array of adaptive and maladaptive behaviors. For example, clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological recruitment of neural processes that normally serve reward-related learning. The studies outlined in the present proposal will examine the molecular mechanisms of appetitive classical conditioning and operant reward learning and thereby provide a deeper understanding of reward-related learning. A more in depth understanding of the mechanisms of reward-related learning may provide insights into related disorders, such as addiction, obsessive compulsive disorder, impulsivity, AD/HD, schizophrenia and eating disorders.
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