Dopaminergic Modulation of Hippocampal-Cortical Interactions in Learning

PROJECT SUMMARY The hippocampus plays a critical role in the formation of episodic memories. The current predominant hypothesis is that memories are gradually established across distributed cortical networks under the influence of hippocampal activity. Dopamine influences memory processing by signaling the motivational salience of behaviorally relevant stimuli and by modulating the plasticity of cortical and hippocampal circuits. However, our understanding of the impact of hippocampal inputs and dopaminergic modulation on cortical circuits during memory processing remains incomplete. Here we propose to use two-photon imaging to characterize the evolution of hippocampal inputs, dopamine dynamics, and neuronal responses in the auditory cortex throughout the formation of associative auditory memories. In addition, we will measure the plasticity of hippocampal inputs and their modulation by dopamine in vivo. Finally, we propose to use a combination of optogenetic and pharmacological perturbations of the hippocampal inputs and dopamine levels in the auditory cortex to determine their functional role in the learning and consolidation of auditory memories. Characterizing hippocampal-cortical interactions and their neuromodulation is of fundamental importance for understanding the circuit mechanisms underlying memory formation and can provide the foundation for elucidating how these mechanisms are perturbed in memory disorders.