UC San Diego

Oscillations in the brain support cognitive functions by synchronizing activity of neuronal populations across large spatial scales. Oscillations therefore aid in communication and information transfer between brain regions. Theta oscillations (6-9 Hz) are large amplitude oscillations in the rodent hippocampus that play a crucial role in facilitating working memory and sensory processing. Theta oscillations can accomplish this function through a number of ways including (1) coordinating with other oscillations in cortical and sub-cortical structures, and (2) regulating the spike timing of neurons within the hippocampus and in associated brain regions like the medial prefrontal cortex. In this dissertation, we investigated both mechanisms to shed light on the role of theta oscillations in memory and sensory processing. In addition to the well-known role of theta oscillations in the prefrontal-hippocampal circuit, respiration-entrained oscillations in the olfactory bulb (OB) have been described in these structures. We first asked whether theta oscillations in the prefrontal-hippocampal circuit get coupled to these respiration-entrained oscillations and thus support sensory processing. We trained mice in an odor-cued working memory task and examined the coupling of theta and respiration-entrained oscillations during the different phases of the task. We found that these oscillations remain uncoupled to each other even when their frequencies match each other and during task phases when communication between these brain regions might be deemed necessary. Having established that coherence between theta oscillations and respiration-coupled oscillations are not necessary for performance in an odor-cued working memory task, we then probed deeper into the role of precise timing of theta oscillations in controlling spike timing within the medial prefrontal cortex (mPFC) during a delayed spatial alternation task. We employed an optogenetic strategy to manipulate the frequency of theta oscillations within the prefrontal-hippocampal network and assessed the effect of these manipulations on mPFC neuronal firing. A subset of the mPFC neurons responded to the artificially paced oscillations by shifting the frequency of their rhythmicity to match the stimulation frequency, specifically during the encoding and maintenance phases of the task. These results suggested that theta oscillations play a crucial role in mediating prefrontal-hippocampal interactions during encoding and maintenance of working memory.