About this Research Topic

Background

Introduction:

The dentate gyrus has long been hypothesized to be a structure integral for the formation of new memories due to its unique connectivity within the medial temporal lobe. Traditionally, it has been thought that one of the primary roles of the dentate gyrus is to reduce interference of memories through the pattern separation of inputs to create distinct outputs. This hypothesized function evolved primarily from aspects of its anatomy and its sparse activity, which then fueled computational models of how dentate gyrus activity affected its local circuits. Many experiments have attempted to identify activity within the dentate gyrus that depicts distinct population codes in the granule cell layer that are more separated than those seen in its upstream or downstream structures. However, proof to support the hypothesized mechanisms through which this separation is accomplished, and experiments that test the impact of such distinct patterns in the activity of downstream structures are far more rare. There is therefore still a great need for a circuit level mechanism approach to studies of dentate gyrus function in which there is a focus upon how the dentate gyrus interacts with other brain structures.

While pattern separation has been an attractive role for dentate gyrus in learning and memory, other hypotheses have implicated the dentate gyrus as critical for a number of other important functions including:

• the formation of engrams
• the emotional consolidation of memories
• the generation of ripples
• the temporal tagging of memories.

A circuit level mechanism approach could potentially unmask other important influences of dentate gyrus upon functions more traditionally ascribed to other downstream subregions of the hippocampus. Moreover, such an approach would greatly aid in tying together these different roles into an integrated, more comprehensive theory of its function.

Topic Proposal:

The goal of this Research Topic is to focus on a more integrated view of dentate gyrus function that is centered on how dentate gyrus activity influences and is influenced by its broader local circuits. Some key questions include, but are not limited to:

1. What is the theoretical and experimental evidence to support mechanisms of how pattern separation is accomplished in dentate gyrus from its inputs and how this separation affects downstream targets?
2. What are the local circuits within dentate gyrus that give rise to its rich oscillatory dynamics, and how might these circuits influence local processing within dentate gyrus and processing throughout the hippocampal circuit?
3. How do reward structures and neuromodulatory inputs influence activity in the dentate gyrus?
4. What role do mossy cells play in the function of dentate gyrus?
5. How do local inhibitory circuits affect the responsiveness of granule cells and downstream CA3 pyramidal neurons to excitatory inputs?
6. How do the physiological properties of adult-born neurons as they mature affect local processing within the dentate gyrus and processing throughout the hippocampal circuit?

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