Research Examines the Function of Different Neural Cell Groups in Mouse Hippocampus During Memory Formation

May 4, 2023 feature

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by Ingrid Fadelli , Medical Xpress

The hippocampus plays a crucial role in forming episodic memories, which are long-term memories of our experiences that we can consciously remember and mentally re-experience. Past neuroscience studies have found that this memory consolidation process, as well as the ability to learn from past experiences, is influenced by the generation of electrophysiological oscillations in the hippocampus, known as sharp-wave ripples (SWRs).

Researchers at Columbia University recently published a paper in Nature Neuroscience, in which they characterized the activity of interneurons in two regions of the hippocampus as mice move in their surrounding environment and their brain is forming new memories. This was done in order to better understand how specific populations of interneurons regulate memory consolidation and learning while animals are actively engaged in activities.

'After memories form, they need to be consolidated or they will vanish,' said Tristan Geiller, one of the researchers who carried out the study, to Medical Xpress. 'One the biggest and long-standing questions in our field relates to identifying what triggers these SWR events. Over the years, inhibitory interneurons have been posited as a major circuit element supporting the generation of SWR, but it is notoriously difficult to experimentally record the activity of these cells in awake behaving animals and test this hypothesis.'

In their recent experiments, Geiller and his colleagues examined the activity of interneurons in the CA3 and CA2 regions of the mouse hippocampus as the animals were awake and moving, using a new method introduced in their previous work. This allowed the researchers to characterize the activity and responses of different sub-types of interneurons as the mice were forming new memories and SWRs were generated in their brain.

For instance, they found that interneurons expressing the protein cholecystokinin were less active before the SWRs took place, while interneurons expressing the protein parvalbumin were highly active after SWR oscillations. 'Recently, it has been shown that not only SWRs are important for memory consolidation, but that the duration of SWR can be predictive of how well an animal remembers, or rather we should say 'how fast an animal learns,'' said Geiller.

While other research teams examined the activity of interneurons in the past, most of their efforts focused on anesthetized rodents or used poorly performing techniques on moving rodents. Geiller and his colleagues' study provides new insights into the role of interneurons in memory consolidation and learning while animals are actively engaged in activities.

'Our paper suggests that the activity of cholecystokinin (CCK)-expressing interneurons (a class of interneurons) in the CA3 region of the hippocampus (where SWR are thought to originate) decreases just before SWR events, and that the magnitude of this decrease is associated with how long the SWR will be. Similarly, we found that parvalbumin (PV)-expressing basket interneurons activity is associated with the termination of SWR events, and reflective of how long the SWR was.'

The recent work by this team of researchers sheds new light on the activity of specific types of interneurons in the hippocampus before, during and after the generation of SWRs, thus contributing to the understanding of memory consolidation and learning processes. In the future, it could pave the way for further studies looking at how distinct interneuron populations influence and regulate learning related SWRs.

'In our next studies we plan to leverage the genetic specificity of these interneuron classes and to manipulate them in a temporally controlled manner with optogenetics,' Geiller added.

'We want to test whether we can artificially increase the duration of SWR events and consequently improve learning in mice. However, we know that CCK and PV interneurons are only one element of the circuit mediating SWR generation. Previous work has also implicated neuromodulation and other subcortical nuclei with this process, so it may be a long time until we fully understand the neural underpinnings of memory consolidation.'

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