Investigating the cellular basis for distinct theta rhythm generators in the dorsal and ventral hippocampus

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Theta rhythm is the most prominent population activity in hippocampus and takes place when the animal is exploring the environment and during REM sleep. This type of rhythm recorded extracellularly occurs at a frequency between 3-12 Hz is known to be essential for memory formation since eliminating it severely impairs memory. Because this type of activity is so important physiologically, understanding the cellular basis of this activity has been a major topic in neuroscience for more than 50 years. The widely accepted model suggests that theta generation in hippocampus is completely dependent on rhythmic neurons located in a ventral brain area named the medial septum. Much to the surprise of everyone in the field, we have shown recently that theta generation in the CA1 area of the hippocampus is a product of neuronal networks located within the hippocampus itself and not in the medial septum. In this proposal, we will further investigate the properties and underlying mechanisms underlying theta rhythm in hippocampus. More precisely, we will investigate the properties of two theta oscillators located in the ventral and dorsal pole of area CA3. This is important since it has been suspected that the ventral and dorsal poles of the hippocampus have much different cognitive roles such that the dorsal pole plays a key role in memory processing whereas the ventral pole is essential for emotional processing. This dissociation of hippocampal function into a memory and emotional pole may be due in part by the distinct brain regions these poles are connected to. Indeed, the dorsal pole is heavily connected to the medial septum and mammilary nuclei whereas the ventral half has unique projections to the prefrontal cortex, amygdala and nucleus accumbens. However, it remains undertermined how the hippocampus can process such different information sumultaneously. We hypothesize that the dorsal and ventral parts of the hippocampus contains dissociable neuronal networks. In addition to investigating the differential cellular mechanisms underlying each generator, we will investigate how they can synchronize with each other. We propose that these dorsal and ventral oscillators can couple depending on the level of plasticity. We will investigate the receptors and the signaling involved in this coupling and uncoupling process. In summary, we propose a physiological substrate to explain how the hippocampus can perform spatial and emotional tasks simultaneously and plan to determine at the cellular level how these dorsal and ventral networks are distinct.