"Cell" sub-journal: the first discovery of the neural circuit of sleep to consolidate social memory, the latest research results of the Chen Xiaowei/Qin Han team of the Army Medical University

*For medical professionals only

As social animals, we can identify and remember other people during social interactions, and we can use these social memories to communicate and make decisions in subsequent social activities [1].

It is not difficult to see that social memory is a necessary condition for normal social interaction and is very important
for human survival and reproduction.

The relationship between sleep and memory has always attracted much attention, and most readers probably have experienced sleep deprivation and memory decline
.

However, the neuronal circuitry needed to consolidate the newly encoded social memory remains unknown
.

Recently, the team of Chen Xiaowei and Qin Han from the Army Medical University discovered the neural mechanism by which rapid eye movement sleep (REM) can consolidate social memory through mouse models [2].

Using techniques such as calcium flow in vivo imaging, optogenetics, and in vivo single-cell electrophysiology, they found that neurons projected by the hypothalamic supramammary nucleus (SuM) into the CA2 region of the hippocampus are highly activated during REM sleep, and that specific inhibition of this group of neurons during REM sleep impairs social memory
.
They also found that neurons that specifically inhibit SuM projection to the dentate gyrus (DG) hippocampus had no significant effect
on social memory during REM sleep.

This work is the first to demonstrate that hypothalamic SuM projection into the hippocampal CA2 neuronal circuit during REM sleep is necessary to
consolidate social memory.
This important study was published online in
the prestigious journal Neuron.

Figure 1: Screenshot of the paper cover

Social memory is the basis for animals to be able to recognize and remember members of the same species [3].

The successful memory formation process includes the encoding of new things in society, the recall of new things and their subsequent consolidation [4].

At present, the neural circuit mechanism of encoding, expression and consolidation of social memory has been studied, but it is not well understood
.

Based on existing research, the current understanding is that hippocampal CA2 neurons are activated when faced with members of new species of external society, and that this is necessary to encode social memory [5].

Furthermore, the encoding of social memory is closely related to the projection of hypothalamic SuM → hippocampal CA2 [6].

CA2 neurons then transmit signals to CA1 on the ventral side of the hippocampus, which may be responsible for storing social memories [7].

For memory consolidation, it is currently known that the reactivation of hippocampal CA3 neurons during sharp wave ripples (SWRs) of non-REM sleep is required for spatial memory consolidation [8].

However, how and through which specific neural circuits social memory is consolidated in the hippocampus remains an unsolved mystery
.
Therefore, Chen Xiaowei and Qin Han's team launched research to try to unravel this mystery
.

So let's follow the singularity cake to see how they carry out their research
.

First, the authors confirmed the presence of neural pathways (SuM CA2 projection neurons) in the hypothalamic SuM→hippocampal^CA2 and SuM→hippocampal DG neural pathways (SuM^DG projection neurons) by virus-specific pathway labeling (Figure 2).

Figure 2.
Virus-specific pathway labeling indicates confirmation of the presence of SuM^CA2 projecting neurons and SuM^DG projecting neuronal pathways

Next, they used retrograde neural tracing to further demonstrate that both groups of neuronal somas are present in SuM, and they found that SuM^{CA2-projecting} neurons and SuM^DG projecting neurons are two different groups
of nerve cells.

Since previous studies had shown that SuM neurons were activated during REM sleep and wakefulness, the authors next wanted to explore whether SuM^{CA2-projecting} neurons or SuM^DG projecting neurons were highly activated
during REM sleep.

To explore this question, they first measured the calcium flow response
of nerve fibers from SuM CA2 projecting neurons or SuM DG projection neurons at^CA2 and^DG using fiber optic recording, respectively.
During this process, EEG and electromyogram recordings allowed them to distinguish between different states in which mice were located, including REM sleep, non-REM sleep, and resting states
.

They found that the nerve fibers of the two groups of neurons were significantly more activated in REM sleep than in non-REM sleep and resting states (Figures 3 and 4).

Figure 3.
SuM^CA2 projection neurons are highly activated during REM sleep

Figure 4.
SuM^DG projection neurons are highly activated during REM sleep

Then, through in vivo single-cell electrophysiology and optogenetic techniques, they showed that these two groups of neuronal somas of SuM (SuM^CA2 and SuM^DG projection neurons) also specifically exhibit a highly activated state
during REM sleep.

Seeing these exciting results, you must want to ask, do SuM^CA2 or SuM^DG projection neurons contribute to the consolidation of social memory?

So, through optogenetic and mouse behavioral studies, the authors explored the role
of these two groups of neurons in the process of social memory consolidation.
They found that if SuM^{CA2-projecting} neurons were specifically inhibited during REM sleep, the mice's social memory declined
significantly.

Specifically, these mice were still more interested in the new social member they had been exposed to (before sleep) than the control group, indicating that they did not develop a corresponding social memory, that is, they did not remember having been exposed to this member before (Figure 5).

In addition, they found that this neural circuit was specifically inhibited during REM sleep and had no effect
on spatial memory consolidation.

Figure 5.
Specific inhibition of SuM^CA2 projection neurons during REM sleep, impairing social memory in mice, does not affect spatial memory

For SuM^DG projection neurons, the authors conducted a similar study
.

They found that if SuM^DG projecting neurons were specifically inhibited during REM sleep, the mice's social memory was not significantly affected, while spatial memory was significantly reduced
.

Overall, this study combines a variety of cutting-edge techniques to directly demonstrate that the hypothalamus and hippocampus are highly active nerve groups during REM sleep, and that the two neural circuits play important roles
in the consolidation of social memory and spatial memory, respectively.

Graphic summary

This research result not only deepens the understanding of social memory consolidation neural circuits, but also provides potential targets for future clinical interventions for different memory disorders
.

References:

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[6].
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A hypothalamic novelty signal modulates hippocampal memory.
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[7].
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[8].
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