Integration of New Memories in the Hippocampal Network

Post by Anna Cranston

What's the science?

The incorporation of new memories without disrupting acquired ones is critical for adaptation and survival. Prior memories have been shown to influence and promote further learning as well as the ability to re-active memories held in the hippocampus network. However, the exact network-level operations underlying cross-memory interaction are not yet known. This week in Nature Neuroscience, Gava and colleagues investigate the organizational mechanisms that allow for the continuous integration and interaction of hippocampal memories.

How did they do it?

The authors took recordings from the dorsal CA1 region of the hippocampus in mice, using microdrives containing electrodes that were surgically implanted at the site of the CA1 hippocampal pyramidal layer. In these recordings, mice were exploring a familiar environment before and after associating a separate, novel environment with a reward (sucrose), using a behavioral test known as the conditioned place preference (CPP) task. They analyzed the compartment preference for the mice that were conditioned by sucrose solution in the CPP task, while simultaneously recording neuronal spiking in these mice. Next, using recordings of spike trains, which are representations of neuronal activity at defined time-points, the authors recorded the mice during active exploration to determine the firing pattern relationships between sets of co-active, or nearby neurons during each task. The authors also constructed mathematical graphs that represent the spike relationships among CA1 principal cells recorded in a given CPP task session. Finally, they analyzed spatial coherence and topology of neuronal cluster firing, to determine grouped firing patterns of neurons (how the neurons co-fire together) that depended on the location of the mice during the task.

What did they find?

Through the spike train recordings obtained during the CPP performance task, the authors found that the new CPP memory reorganized pre-existing hippocampal firing topology. In addition, through a principal component analysis of co-firing maps generated from recordings throughout the CPP tasks, they found that the co-firing maps could be described by three principal components (in other words, the data varied primarily along three axes in three ways): 1) Similar co-firing patterns could be seen across different sessions in the same environment, indicating the location of the memory and considered to represent the core or main part of the memory, 2) Different co-firing patterns described different aspects of the behavioural task/CPP sessions, and 3) Different co-firing patterns differentiated between exposure and re-exposure to an environment. Overall, new memories obtained during the CPP task influenced existing firing patterns of hippocampal neurons representing prior memory. Finally, the authors found that high- and low-activity cells contribute differently to these hippocampal network co-firing axes, working together to segregate memories by space, novelty, and events.

What's the impact?

This study investigated the topology of neuronal co-activity and found that memory information spans multiple functional axes of the neuronal network in the mouse hippocampus. Their findings reveal underlying principles of organization for how memories are integrated, and provide novel insights into the division of labor between distinct types of hippocampal neurons.  

Gava et al. Integration of New Memories in the Hippocampal Network. Nature Neuroscience (2021). Access the original scientific publication here.