Emotional responses are made up of the hippocampus, including the hippocampus（hippocampus, hpc）and amygdala（amygdala, amy）The loops of the limbic system are generated. In the human brain, wave (13-30Hz) communication between these structures is associated with self-reported mood and anxiety. However, the mechanism and significance of this biomarker as a marker or driver of emotional state remains unknown.
January 23, 2023, University of California, San Franciscovikaas s. sohalThe professor is inneuronpublished an article titled“amygdala-hippocampus somatostatin interneuron beta-synchrony underlies a cross-species biomarker of emotional state”Research**. Among them, Adam DJackson is the first author of this article.
Here, the researchers showed that wave communication between the ventral hippocampus (VHC) and the basolateral amygdala (BLA) can also contribute to anxiety-related behaviors in mice, both on longer time scales (30 minutes) and before immediate behavioral selection. Genetically encoded voltage indicators (GEVI) suggest that this biomarker reflects the synchrony between somatostatin (SST) interneurons in VHC and BLA. In fact, synchronization between these neurons can dynamically approach and avoidance decisions, and the use of optogenetics to change the synchronization phase for just 25 milliseconds is sufficient to modulate anxiety-related behavior in both directions.
Thus, this translational study from clinical to basic establishes human biomarkers as causal determinants of emotional state(and not just the ** factor)., revealing a novel mechanism by which frequency, phase, and cell type-specific inter-region synchronization controls emotional processing.
-Coherence bursts are able to act as miceBiomarkers of anxiety in humans
The -coherence difference between AMY and HPC was able to track mood and anxiety in humans, and they first tried to test whether it was also able to ** anxiety levels in rodents. Therefore, they first recorded local field potential (LFP) from BLA and VHC in rearing cages to calculate the difference between BLA and VHC -coherence, and compared their correlation with zero maze (EZM) performance. They found thatThe differences in AMY-HPC-coherence before the experiment, especially -coherence bursts, showed a significant negative correlation with the time of the EZM open arm region.
Using a dataset originally published from patients with epilepsy, the researchers found transient, high -coherence bursts in human intracranial electroencephalogram (IEEG) recordings (Figure 1A). In human data, there was a strong positive correlation between the number of -coherence bursts and the difference in AMY-HPC -coherence (Fig. 1b). In addition, the occurrence of -coherence bursts was strongly negatively correlated with subjective scores of mood and anxiety (Immediate Mood Scaler (IMS; Figure 1c). Correspondingly, recordings of negative emotional states (high IMS) contain more -coherence bursts than positive emotional states (low IMS) (Figure 1D). To sum up,These studies have shown that -coherence bursts are associated with anxiety in humans and mice.
Between SST+ neurons in BLA and HPCSynchronicity is associated with mood anxiety
To test whether -Coherence Burst may play a role in anxiety-related behaviors on rapid behavior-related time scales, the researchers employed an elevated plus maze (EPM) paradigm and recorded LFP signals between BLA and VHC at the open and closed arms of mouse exploration (Figure 2A).
The researchers observed that the time-locked probability of -coherence bursts increased before avoiding the open-arm environment; This increase in time-lock is not present when mice approach (rather than avoid) the open-arm region (Figure 2B-C).
Then, using trans-membrane electrical measurements performed optically (tempo), the researchers found that the activities of VHC and BLA SST+ interneurons were synchronized with -coherence bursts in transgenic mice with Gevi virus and SST-Cre. Rather than parvalbumin (PV)-expressing interneurons.
Given that VHC-BLA-SST is synchronized with -Coherence bursts, and -Coherence bursts are associated with anxiety-related avoidance behaviors, the researchers further examined whether the synchronicity of SST+ interneurons is also associated with anxiety-related behaviors. The researchers found out through EPM experiments and simultaneously recording the corresponding LFP signalsThe synchronicity of SST+ interneurons increases before avoiding the open-arm behavior and ending the open-arm exploratory behavior.
VHC-BLA-SST+ interneuron synchronywithCausality of anxiety-like behavior
Furthermore, the researchers increased or decreased anxiety-related behaviors (avoidance of open arms, reduced risk behaviors) in EPM by activating or disrupting VHC-BL-SST+ interneuron synchrony through optogenetics. Moreover, inhibition of BLA-SST+ interneurons reduced -coherence bursts and anxiety-related avoidance (Fig. 3 a-e).
This series of results suggests that BLA-SST+ interneurons appear to play a key role in initiating the synchronization of BLA and VHC circuits, and therefore there may be long-term direct inhibition of BLA-SST+ interneurons to VHC targets, including SST+ interneurons. To confirm this, the researchers recorded the suppressive current from BLA to VHC by patch-clamp technique (Figure 3 F-G), demonstrating the existence of this functional loop.
Taken together, this study found that synchronization between AMY and HPC is a cross-species biomarker of emotional state, and that this synchronization is driven by the synchronicity of the SST+ interneuron population(Figure 4).