UC Riverside

Neuronal circuits maintain a delicate balance of excitatory drive and inhibitory regulation to execute high order functions, such as learning and memory, and maintain network stability which is severely compromised in temporal lobe epilepsy (TLE). The hippocampal dentate gyrus (DG) acts as a functional gate into the hippocampal trisynaptic circuit and plays a key role in learning and memory. Formation of memories is believed to be coded by activity of a distinct collection of neurons which represent a memory or experience known as an engram. Sparse activity in dentate granule cells (GCs) has been shown to be involved in engram formation; however, the circuit mechanism that underlie formation of these neuronal activity patterns are not fully understood. Recent studies have found that a sparse subtype of dentate projection neurons, semilunar granule cell (SGC) are preferentially recruited in engrams. SGCs differ from GCs in their wide dendritic arbors, molecular layer axon collaterals and persistent firing and have been proposed to support feedback inhibition of GCs. However, circuit connectivity and functional effects of SGCs are not known. The objective of this dissertation is to better understand SGC’s role in the dentate circuit, their role in DG circuit processing as well as alterations to their synaptic inputs epilepsy. I hypothesized that SGCs refine GC engrams by driving a subset of GCs in the engram and supporting feedback inhibition of surrounding “non-engram” GCs. My findings indicate that SGCs have more frequent excitatory inputs, with higher inputs from the medial entorhinal cortex (known to contain spatial information). I report that SGCs are reliably recruited as part of a spatial engram due to its heightened excitability compared to GCs. GCs and SGCs adapt differently in response to pilocarpine induced epilepsy and epileptic mice are unable to use a spatial search strategy in our special behavior paradigm. These studies provide novel fundamental insights into dentate circuit function and memory processing.