Temporal Coding in the Dentate Gyrus


Outcome:
TDLC’s Lara Rangel, Andrew Alexander, Brad Aimone, Janet Wiles, Rusty Gage, Andrea Chiba, and Laleh Quinn have discovered that granule cells in the dentate gyrus of the hippocampus encode the temporal separation between experiences that occur over long periods of time. Working from a model developed by Aimone, Wiles, and Gage, they tested the hypothesis that the continual addition of newborn neurons in the adult dentate gyrus enables the temporal tagging of memories. They showed that both the length of time between experiences and the levels of adult neurogenesis during the different experiences affected the ability of neurons in the dentate gyrus to exhibit activity selective to a given experience. It was previously unknown that the dentate gyrus could temporally distinguish between experiences in this manner. Their data reveal the existence of a temporal orthogonalizing neuronal code within the dentate gyrus, a hallmark feature of episodic memory.


Impact/benefit:
Episodic memory requires the ability to distinguish events that are experienced at different times, in other words, knowing what happened when. This data indicates that the addition of new neurons into the adult dentate gyrus is an important component of temporally encoding experiences. Thus, facilitating neurogenesis could have benefits for episodic memory formation. Many things impact the ability to form and sustain new neurons in adulthood including exercise, environmental enrichment, and diet. It is now known that adult neurogenesis can continue throughout our lifespan, even into old age. If steps are taken to increase the chance of creation and survival of new neurons, deficits in episodic memory that occur with aging and other disorders may be alleviated.

 

Explanation:
A recent model of the hippocampus by Aimone et al. predicted that the unique properties of the dentate gyrus allow for the temporal separation of events. According to their hypothesis, this temporal separation is accomplished in part through the continual generation of new neurons, which, due to a transient window of hyperexcitability, allows for preferential encoding of information present during theirdevelopment. Rangel et al used invivoelectrophysiological recordings to test their prediction and identified a cell population exhibiting activity that was selective to single behavioral contexts when ratsexperienced a long temporal separation between context exposures during training. Thisselectivity was attenuated as the temporal separation between context exposures was shortened. To test the contribution of newborn neurons to context selectivity, temozolomide (a chemotherapeutic agent that kills dividing cells) was utilized to knockdown neurogenesis. Selectivity was further attenuated when neurogenesis was reduced in this manner.

Figure: The dentate gyrus uses distinct populations of neurons to timestamp experiences that occur over long periods of time.

 




Rangel LM, Alexander AS, Aimone JB, Wiles J, Gage FH, Chiba AA, Quinn LK. Temporally selective contextual encoding in the dentate gyrus of the hippocampus. Nat Commun. 2014;5:3181. doi: 10.1038/ncomms4181.