@article{Dopaminergic:10107,
      recid = {10107},
      author = {Heer, Chad Michael},
      title = {Dopaminergic Modulation of Hippocampal CA1: Uncovering the  Activity Dynamics of VTA and LC Inputs during Behavior and  Learning},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2023-12},
      pages = {160},
      abstract = {Dopaminergic activity in the hippocampus modulates  synaptic plasticity, alters place cell activity, and affects  hippocampal dependent learning and memory processes.  Traditionally these effects were attributed to the release  of dopamine from sparse projections originating in the  ventral tegmental area (VTA) and extending to the  hippocampus. However, the role of VTA inputs in  dopaminergic modulation of the hippocampus has recently  been brought into question, as denser inputs from the locus  coeruleus (LC) have been shown to release dopamine in the  dorsal hippocampus, and impact hippocampal dependent  learning and memory. To dissect the impacts of both VTA and  LC dopaminergic circuits on hippocampal activity and  memory, we functionally imaged the activity of VTA and LC  axons in dorsal CA1 (dCA1). During spatial navigation, VTA  inputs exhibited a ramping to reward signal that depended  on the animals’ reward expectation. Inhibiting VTA  dopaminergic neurons largely replicated the effects of  reward expectation extinction: reducing overrepresentation  of rewarded locations, inducing place field remapping, and  decreasing place field trial-to-trial reliability. We  conclude that reward expectation restructures CA1 place  cells and determines map reliability through the modulation  of dopaminergic VTA-CA1 reward proximity signals. In  contrast, LC inputs were devoid of the reward-proximity  signal observed in VTA axons and instead exhibited velocity  correlated activity and increases in activity prior to  motion onset. Interestingly, a marked divergence emerged in  novel VR environments. LC axon activity sharply and  persistently increased for over a minute, while the  previously observed VTA axon reward-proximity signal  disappeared. We conclude that LC inputs to dCA1 encode the  animals’ brain state, as changes in behavior and  environmental novelty are associated with heightened  arousal. This observation further strengthens the roles of  LC neurons in influencing brain states and in novelty  encoding in the hippocampus. Together, these findings  demonstrate VTA and LC inputs encode unique information,  likely contributing todifferential modulation of hippocampal  activity during behavior and learning.},
      url = {http://knowledge.uchicago.edu/record/10107},
      doi = {https://doi.org/10.6082/uchicago.10107},
}