Persistent Hyperdopaminergia Decreases the Peak Frequency of Hippocampal Theta Oscillations during Quiet Waking and REM Sleep

Kafui Dzirasa, Lucas M. Santos, Sidarta Ribeiro, Jennifer Stapleton, Raul R. Gainetdinov, Marc G. Caron, Miguel A. L. Nicolelis

Long-term changes in dopaminergic signaling are thought to underlie the pathophysiology of a number of psychiatric disorders. Several conditions are associated with cognitive deficits such as disturbances in attention processes and learning and memory, suggesting that persistent changes in dopaminergic signaling may alter neural mechanisms underlying these processes. Dopamine transporter knockout (DAT-KO) mice exhibit a persistent five-fold increase in extracellular dopamine levels. Here, we demonstrate that DAT-KO mice display lower hippocampal theta oscillation frequencies during baseline periods of waking and rapid-eye movement sleep. These altered theta oscillations are not reversed via treatment with the antidopaminergic agent haloperidol. Thus, we propose that persistent hyperdopaminergia, together with secondary alterations in other neuromodulatory systems, results in lower frequency activity in neural systems responsible for various cognitive processes.