Cell︱Breakthrough! The new mechanism of human brain spatial navigation and memory: phase precession of hippocampus and entorhinal cortex

Written by Wang Sizhen, edited by Wang Sizhen, the spatial navigation and episodic memory of Wang Sizhen's brain are very important to human daily activities
.

For example, "Where am I? Where have I been? Where am I going?" Our brain has the ability to encode these related events and associate them in an orderly manner.
A potential neural mechanism of this ability is phase precession.
(Phase precession) [1]
.

Phase precession is a neurophysiological process that refers to the phase relationship between action potentials (discharges) and periodic rhythm field potentials (such as local theta oscillations) of some special neurons (such as the spatial adjustment cells of the hippocampus of the brain).
Phase precession is believed to play an important role in the neural coding of information [2-3]
.

 The spike timing (or spike timing) of hippocampal neurons is very important for the connection between events in the learning sequence [4]
.

The pulse timing can be coordinated by the oscillation of large-scale network activity, and this activity fluctuation can be detected by local field potential (LFP) [5-6]
.

Therefore, the consistent relationship between network oscillations and individual neuron pulses may contribute to the coding sequence, which can play a role in complex behaviors or cognitive aspects (such as memory) [7]
.

 In rodents, the activity of hippocampal neurons through phase precession shows a coordinated relationship between LFP and pulse timing, which suggests that phase precession may be a potential mechanism for the integration and processing of sequence events [1]
.

Studies have also suggested that the phase precession may compress and process the spatial trajectory on the behavioral scale into a short theta oscillation period that is conducive to synaptic plasticity [8]
.

 In addition to representing spatial features, phase precession can also represent non-spatial features by integrating and processing the underlying mechanisms of sequence events, participating in or relating to some neural representations of brain regions, thereby supporting different aspects of cognition, learning, and memory [9- 10]
.

Although many theories and studies suggest that phase precession plays a very important role in neural coding, the current research is almost only focused on rodent models [11]
.

So, is phase precession also common in humans? And play an important function? On May 11, 2021, in the latest paper published online in Cell titled Phase precession in the human hippocampus and entorhinal cortex, Salman E.
Qasim of Columbia University (first article), Joshua Jacobs (corresponding author) and California Itzhak Fried of the University of Los Angeles collaborated on these scientific issues
.

The study found that human brain neurons use the rhythmic pulse timing of local network oscillation to represent spatial location and non-spatial state, and emphasized that phase advancement is a common neuronal mechanism for coordinating behavior and pulse timing in cognitive processes
.

 The study recruited 13 patients with drug-resistant epilepsy (hereinafter referred to as subjects) and asked them to perform navigation tasks for specific destinations in a virtual environment
.

As shown in the figure below, there are 6 target shops around the square, and there are obstructive buildings on both sides of the target.
The subject can move clockwise or counterclockwise along the track while recording the subject’s navigation at the destination.
Process the spatial and non-spatial phase precession of neurons in the hippocampus, entorhinal cortex, etc.
, and analyze the relationship between neuron firing and phase precession in navigation tasks
.

The top view of the virtual task environment (red squares indicate possible target locations) (picture quoted from: Qasim et al.
, Cell 2021; 184: 1-14) First of all, the author noticed that, compared to rodents, humans are in the process of spatial navigation The phase precession is more intense, and this is related to the high firing frequency of the neuron; compared with the navigation time, 12% (35/296) of the human space adjusts the relationship between the phase precession of the neuron and the navigation position These neurons are mainly located in brain areas such as the hippocampus and inner nasal cortex, which suggests that this spatial phase precession may be a relatively common phenomenon; the correlation between position and phase is obviously stronger than The correlation between the discharge frequency and the phase indicates that the pulse-phase encoding (capacity) of the spatial position information is stronger than the encoding (capacity) of the spatial position information of the discharge frequency
.

 Secondly, although the phase precession in a specific spatial position of the brain is the most obvious, there are also phase precessions in the brain regions of non-spatial behavior and non-spatial stimulation, and brain regions outside the hippocampus, which implies that the phase precession of the brain may be A common phenomenon [10, 12]
.

Here, the author measured the pulse frequency of neurons with firing but no spatial adjustment in the navigation task, and after comparing and analyzing with the continuous LFP, it was found that 20% (146/744) of the navigation task had non-spatial adjustment.
There is a significant relationship between the LFP frequency and pulse frequency of neurons, and among the 20% non-spatially adjusted neurons, 62% (90/146) neurons have obvious phase precession
.

Therefore, phase precession also exists in neurons that encode non-spatial position information, which is a common phenomenon
.

 Finally, the author found that only when subjects were navigating specific targets, 11% (49/448) of the non-spatial adjustment neurons would selectively and clearly show phase precession to encode and correlate the navigation process.
Learning and memory trajectories.
These neurons are mainly concentrated in the anterior cingulate, orbitofrontal lobe, amygdala, hippocampus and other brain regions.
This specific target phase precession may represent a unique kind of neuron spatial phase precession The process of nerve cell activity
.

On the other hand, these findings also indicate that the specific non-spatial phase precession in the navigation (trajectory) of a specific target may represent some non-spatial, ordered behavior or stimulus characteristics
.

 Article pattern diagram: Phase precession is an important spatial and non-spatial neural coding mechanism across species and multiple brain regions (picture quoted from: Qasim et al.
, Cell 2021; 184: 1–14) Article conclusion and discussion This research provides evidence for the spatial phase precession of the human hippocampus and entorhinal cortex during virtual navigation, and the human spatial phase precession shows similar characteristics to rodents.
The research also shows that the specific target navigation task (trajectory) Non-spatial phase precession exists specifically
.

Therefore, phase precession is a universal neural mechanism for encoding non-spatial location information in the human brain
.

In addition, the research also suggests that the phase precession of a specific target has a potential relationship with a series of physiological experience characteristics (experiential learning and memory during navigation)
.

 Of course, this research still has some flaws in its beauty, and it also brings some enlightenment for future research
.

1.
Although it is proved that there is phase precession in humans, unlike rodent phase precession research (method), human phase precession research (method) adopts a wider frequency band standard and looser spatial adjustment Therefore, there are potential differences between rodent and human phase precession studies (results).
How to reasonably connect the two studies (results) will be a challenge for future work
.

2.
Although the research suggests the universality of phase precession, that is, both spatial and non-spatial phase precession exist in humans, it is necessary to further prove this universality, such as choosing animals with low-frequency brain activity similar to humans (such as bats).
And non-human primates)
.

(3) The subject in the study is a patient with epilepsy, and the subject is allowed to perform spatial navigation tasks in a virtual environment.
Then, whether the brain phase precession pattern of the epilepsy patient is similar to that of other humans (healthy people or patients with other diseases) same? Is the phase precession pattern of the real environment (navigation task) the same or different from the phase precession pattern of the virtual environment (navigation task)? In summary, this study shows that phase precession is a spatial (spatial cognition and memory) and non-spatial (experience) that spans species (sawtooths to humans) and multiple brain regions (hippocampus, inner nasal cortex, etc.
) Sexual characteristics) important neural coding mechanism
.

Original link: https://doi.
org/10.
1016/j.
cell.
2021.
04.
017 Selected articles from previous issues [1] PNAS︱ A new hope for visual restoration? CXCR4/CXCL12 signal-mediated new mechanism of damaged optic nerve regeneration [2] Sci Transl Med︱ a new mechanism to improve the pathology of Alzheimer’s disease [3] Alzheimer's Dementia︱ the latest scientific hypothesis! JNK is a therapeutic target for neurodegenerative diseases [4] Nat Neurosci︱ for the first time! Neuronal ApoE affects immune response genes to cause a new mechanism of AD pathology [5] Nat Immunol︱ perspective challenge! Microglia phagocytosis mediated Amyloid plaques may have a protective effect [6] Interpretation of how Nature︱ impaired meningeal lymphatic function affects microglia response and anti-Aβ immunotherapy high-quality scientific research training courses recommended [1] "Research Image Processing and Mapping" offline : June 26-27, Shanghai; July 10-11, Beijing [2] Patch clamp and optogenetic and calcium imaging technology seminar (June 26-27, two days and one night) References (slide up and down to view ) [1] O'Keefe, J.
, and Recce, ML (1993).
Phase relationship between hippocampal place units and the EEG theta rhythm.
Hippocampus 3, 317–330.
[2] Hafting, T.
, Fyhn, M.
, Molden, S.
, Moser, M.
-B.
, and Moser, EI (2005).
Microstructure of a spatial map in the entorhinal cortex.
Nature 436, 801–806.
[3] Reifenstein, ET, Kempter, R.
, Schreiber, S.
, Stemmler, MB, and Herz, AVM (2012).