Effects of pharmacological manipulations on activity in the medial entorhinal cortex
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Animal research involving the effects of anxiolytics on theta oscillations has focused on changes in theta frequency in the hippocampus, rather than effects in medial entorhinal cortex (MEC), which provides the cortical input to the hippocampus and is the source of Type I (movement-related) theta rhythm. Neurons coding spatial location, including “grid cells,” are found in the MEC and aspects of their spatial modulation have been linked to theta rhythm in different ways. Theta frequency recorded in the local field potential (LFP) is also strongly correlated with running speed and is used in specific computational models of grid cell firing. Manipulating theta frequency through administration of anxiolytics offers a unique method of examining regulation of the LFP frequency in the MEC, along with the effects of changes in theta frequency on grid cells and other cell types in the region. In addition, the role of the medial septum (MS), which is necessary for theta rhythm in both the MEC and hippocampus, can be investigated by infusing anxiolytics directly into the MS. In this thesis, two separate anxiolytic drugs were tested: a serotonin 1A receptor agonist, 8-OH-DPAT, and a classic benzodiazepine, diazepam, the results of which are described in chapters 2 and 3, respectively. Systemic injections of either drug caused a reduction in theta frequency across all running speeds, resulting in a decrease in the y-intercept of the linear fit to the plot of theta frequency over different running speeds. However, only MS infusion of 8-OH-DPAT, not diazepam, significantly decreased the y-intercept in the MEC. Together, these results expand detection of anxiolytic drug action on theta frequency to a new structure, the MEC, when drugs are given systemically, but demonstrate a dissociation between drug types in their ability to produce effects when infused into the MS. Grid cell firing patterns were unaffected and very few effects were found in single unit firing across different cell types. Overall, these results support predictions made by specific computational models and highlight the involvement of the MEC in the anxiolytic-induced decrease in theta frequency phenomenon uniquely tied to the action of these drugs.