How Informative Are Spatial CA3 Representations Established by the Dentate Gyrus?

In the mammalian hippocampus, the dentate gyrus (DG) is characterized by sparse and powerful unidirectional projections to CA3 pyramidal cells, the so-called mossy fibers. Mossy fiber synapses appear to duplicate, in terms of the information they convey, what CA3 cells already receive from entorhinal cortex layer II cells, which project both to the dentate gyrus and to CA3. Computational models of episodic memory have hypothesized that the function of the mossy fibers is to enforce a new, well separated pattern of activity onto CA3 cells, to represent a new memory, prevailing over the interference produced by the traces of older memories already stored on CA3 recurrent collateral connections. Can this hypothesis apply also to spatial representations, as described by recent neurophysiological recordings in rats? To address this issue quantitatively, we estimate the amount of information DG can impart on a new CA3 pattern of spatial activity, using both mathematical analysis and computer simulations of a simplified model. We confirm that, also in the spatial case, the observed sparse connectivity and level of activity are most appropriate for driving memory storage – and not to initiate retrieval. Surprisingly, the model also indicates that even when DG codes just for space, much of the information it passes on to CA3 acquires a non-spatial and episodic character, akin to that of a random number generator. It is suggested that further hippocampal processing is required to make full spatial use of DG inputs.Author Summary: The CA3 region at the core of the hippocampus, a structure crucial to memory formation, presents one striking anatomical feature. Its neurons receive many thousands of weak inputs from other sources, but only a few tens of very strong inputs from the neurons in the directly preceding region, the dentate gyrus. It had been proposed that such sparse connectivity helps the dentate gyrus to drive CA3 activity during the storage of new memories, but why it needs to be so sparse had remained unclear. Recent recordings of neuronal activity in the dentate gyrus (Leutgeb, et al. 2007) show the firing maps of granule cells of rodents engaged in exploration: the few cells active in a given environment, about 3% of the total, present multiple firing fields. Following these findings, we could now construct a network model that addresses the question quantitatively. Both mathematical analysis and computer simulations of the model show that, while the memory system would function also otherwise, connections as sparse as those observed make it function optimally, in terms of the bits of information new memories contain. Much of this information, we show, is encoded however in a difficult format, suggesting that other regions of the hippocampus, until now with no clear role, may contribute to decode it.