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Written by ︱ Ying Zhang editor in charge ︱ Plate made by Wang Sizhen ︱ Jiaxue Zha The global population is entering an aging stage, and the number and proportion of the elderly population in almost every country in the world is increasi.
As people age, cognitive function usually declines gradually [
Although the mechanism by which aging affects cognitive function is still unclear, scientists have used functional magnetic resonance imaging to find that the shape, size, and functional connectivity of some brain regions are related to cognitive impairment with a.
correlation [1-
Among them, a very interesting brain area is the anterior thalamus (ATN) [
The researchers destroyed the frontal thalamus of mice or used chemical genetics to inhibit the function of the frontal thalamus and found that the cognitive learning ability of mice was significantly reduced [5-1
However, the mechanisms of the anterior thalamus in cognitive processes and in aging remain uncle.
The anterior thalamus can be divided into different subregions: anterior dorsal thalamus (AD), anterior ventral thalamus (AV), and anterior medial thalamus (A.
Due to the lack of specific regulatory means, the role of different subregions of ATN in cognitive function has not been studi.
On May 10, 2022, Guoping Feng's lab from MIT published an article entitled "Anterior thalamic circuits crucial for working memory" on PNAS, with Dheeraj.
Roy and Ying Zhang as the co-first authors of the pap.
Using the laboratory's latest transgenic mice, the team found that AV specifically mediated the storage of working memory by specifically regulating different subregions of the anterior thalamus; with the aging of mice, working memory declined, accompanied by the anterior thalamus Decreased neuronal excitability; increasing the activity of this group of neurons using optogenetic methods can significantly improve working memory in aged mi.
In the article, the researchers used the T-maze test device to study the working memory function of mi.
Using C1ql2-Cre transgenic mice [11], the researchers used optogenetic methods to specifically inhibit different subregions of the anterior thalamus and found that AD was specifically involved in working memory encoding, AV was specifically involved in working memory storage, and specific inhibition was Neither AD nor AV affected information retrieval from working memo.
Furthermore, the Cal-light method was used to label neurons active in different periods of working memory, and it was found that the number of labeled AV neurons increased significantly during the storage period of working memo.
These results suggest an important role of AV neurons in the information storage period of working memory (F.
Figure 1 AV participates in the storage period of working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) The brain is a huge network, and the neural connections of various brain regions are intricately connect.
Next, scientists wanted to know how AV affects working memory through neural circui.
Previous studies have shown that AV can project to various regions outside the thalamus, such as the cortex and the infracerebral peduncle [1
Using optogenetic methods to inhibit different AV circuits, it was found that AV projections to the parasubiculum (PaS) were specifically involved in working memo.
Because PaS can project abundantly to the entorhinal cortex (EC), which is considered to be one of the most important learning and memory centers in the brain [13], the researchers reasoned that PaS neurons projecting to the EC could receive Neuronal regulation from .
We tested this hypothesis using neural circuit traci.
Meanwhile, optogenetic inhibition of the ATN→PaS→EC loop significantly affected the working memory function of mi.
Through the regulation of different loops, the researchers found the AV loop that plays a role in working memory (Figure
Figure 2 The AV→PaS loop is involved in the storage period of working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Since inhibiting the activity of AV neurons will damage working memory, increasing the activity of AV neurons can Does it enhance working memory in mice? Using the same optogenetic method, the researchers excited the AV neural circuit in different stages of working memory and found that light stimulation of the ATN→PaS circuit during the memory storage period can significantly improve the working memory of mice (F.
Figure 3 Exciting AV neurons can improve working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Although some studies have revealed that abnormal frontal thalamic function is associated with reduced executive function in the elderly [4], the specific The mechanisms underlying the dysfunction of thalamic circuits in aging-related disorders have not been investigat.
The researchers first confirmed that working memory function in older mice declined significantly compared to younger mi.
Meanwhile, using brain slice electrophysiology, the researchers found that the activity of AV neurons was reduced in aged mi.
So, if artificially boosting the activity of this group of neurons can improve working memory in older mice? The answer is y.
Increasing the excitability of AV neurons or stimulating the ATNàPaS neural circuit can improve the working memory function of mi.
It is worth noting that the prefrontal cortex (PFC) is considered to be an important brain area for working memory [1
Exciting the PFC of old mice can also improve working memory in mice, but it improves anxiety-like behaviors in mice, which This "side effect" does not exist when the ATN→PaS neural circuit is excit.
These results suggest that the abnormality of working memory in aged mice can be improved by modulating AV neurons or AV neural circuits (F.
Figure 4 Regulation of AV neurons or neural circuits can improve working memory in aged mice (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Conclusions and discussions of the article, inspiration and prospects for this study combined with optogenetic methods The important role of the frontal thalamus in working memory was revealed, and it was found that the specific thalamic circuit ATN→PaS→EC (frontal thalamus→hemicephalic inferior peduncle→entorhinal cortex) was involved in the storage of working memo.
Modulating this circuit can improve working memory abnormalities in aged mice without affecting other behaviors of the mi.
Therefore, the anterior ventral region (AV) may be a potential brain region for the treatment of working memory abnormaliti.
We know that many diseases such as schizophrenia and Alzheimer's disease are accompanied by abnormal working memo.
Interestingly, scientists found a decrease in the number of frontal thalamic neurons in some brain samples from patients with schizophren.
Whether AV plays a role in schizophrenia or other disorders of working memory loss remains to be studi.
Researchers use optogenetic methods to regulate neuronal activity, but this method is currently difficult to apply clinical.
If the corresponding molecular targets can be found, the development of non-invasive therapeutic methods would be a meaningful breakthrough
Link to the original text: https://d.
org/11073/pn.
2118712119 In this article, postdoctoral fellows Dheeraj.
Roy and Zhang Ying are the co-first authors, and Professor Feng Guoping, Dheeraj.
Roy, and Zhang Ying are the co-corresponding autho.
Feng Guoping (left), Dheeraj.
Roy (middle), Zhang Ying (right) (photo courtesy of MIT Feng Guoping Laboratory) Talent Recruitment [1] "Logical Neuroscience" is looking for associate editor / editor / operation Post (online office) Selected articles from previous issues【1】Autophagy︱Ye Yihong’s research group reveals new molecular mechanism of neuronal ceroid lipofuscin deposition: DNAJC5/CSPα gene mutation leads to lysosomal homeostasis imbalance【2】J Neuroinflammation | Wang Yilong's team reports new evidence on the relationship between blood inflammatory markers and cerebral small vessel disease 【3】Science︱Neural mechanism of non-cued goal-directed behavior 【4】Front Psychiatry︱Yang Zhi group reports a state anxiety tracking model with high temporal resolution 【5】Review of Neural Regen Res︱The advantages of Rho kinase and its inhibitor Fasduil in the treatment of neurodegenerative diseases 【6】Nat Neurosci︱He Yanlin/Xu Yong team reported the new mechanism of anorexia nervosa 【7】Transl Psychiatry︱Wang Xueyi The team has made new progress in the study of the brain mechanism of the impact of early-life stress on cognitive function in adulthood【8】Nat Neurosci︱Song Juan’s team revealed that the hypothalamic circuit regulates hippocampal neurogenesis, promotes memory retrieval and fights anxiety-like behaviors【9】Mol Psychiatry︱ Shi Yun/Xu Zhengfeng/Yang Jianjun's team revealed a new mechanism of glutamate receptor mutation impairing cognition【10】Cereb Cortex︱Li Changqi's team revealed the role and mechanism of light-intensity exercise in promoting cued fear memory loss in mice [1] Symposium on Single-Cell Sequencing and Spatial Transcriptomic Data Analysis (Tencent Online Conference on June 11-12) [2] Seminar on Patch Clamp and Optogenetics and Calcium Imaging Technologies May 21-22 Tencent Conference Reference Literature (swipe up and down to read)Harada CN, Natelson Love MC, Triebel KL (2013) Normal cognitive agi.
Clin Geriatr Med 29:737-75 Murman DL (2015) The impact of age on cogniti.
Semin Hear 36:111 -12 Hughes EJ, et .
(2012) Regional changes in thalamic shape and volume with increasing a.
Neuroimage 63:1134-114 Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E (2007) Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging stu.
Am J Neuroradiol 28:226-23 Aggleton JP, Keith AB, Sahgal A (1991) Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in ra.
Behav Brain Res 44:151-16 Warburton EC, Aggleton JP (1999) Differential deficits in the Morris water maze following cytotoxic lesions of the anterior thalamus and fornix transecti.
Behav Brain Res 98:27-3 Mitchell AS, Dalrymple-Alford JC (2006) Lateral and anterior thalamic lesions impair independent memory syste.
Learn Mem 13:388-39 Savage LM, Hall JM,Vetreno RP (2011) Anterior thalamic lesions alter both hippocampal-dependent behavior and hippocampal acetylcholine release in the r.
Learn Mem 18:751-75 Winter SS, Clark BJ, Taube JS (2015) Disruption of the head cell direction network impairs the parahippocampal grid cell sign.
Science 347:870-871 Nelson AJD, Kinnavane L, Amin E, O'Mara SM, Aggleton JP (2020) Deconstructing the direct reciprocal hippocampal-anterior thalamic pathways for spatial learni.
J Neurosci 40:6978- 6991 Roy DS, et al (2021) Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease mode.
Neuron 109:2590-2601 Jankowski MM, et al (2013) The anterior thalamus provides a subcortical circuit supporting memory and spatial navigati.
Front Syst Neurosci 7:41 Yamamoto J, Suh J, Takeuchi D,Tonegawa S (2014) Successful execution of working memory linked to synchronized high-frequency gamma oscillatio.
Cell 157:845-851 Lara AH, Wallis JD (2015) The role of prefrontal cortex in working memory: A mini revi.
Front Syst Neurosci 9:17 End of this article
As people age, cognitive function usually declines gradually [
Although the mechanism by which aging affects cognitive function is still unclear, scientists have used functional magnetic resonance imaging to find that the shape, size, and functional connectivity of some brain regions are related to cognitive impairment with a.
correlation [1-
Among them, a very interesting brain area is the anterior thalamus (ATN) [
The researchers destroyed the frontal thalamus of mice or used chemical genetics to inhibit the function of the frontal thalamus and found that the cognitive learning ability of mice was significantly reduced [5-1
However, the mechanisms of the anterior thalamus in cognitive processes and in aging remain uncle.
The anterior thalamus can be divided into different subregions: anterior dorsal thalamus (AD), anterior ventral thalamus (AV), and anterior medial thalamus (A.
Due to the lack of specific regulatory means, the role of different subregions of ATN in cognitive function has not been studi.
On May 10, 2022, Guoping Feng's lab from MIT published an article entitled "Anterior thalamic circuits crucial for working memory" on PNAS, with Dheeraj.
Roy and Ying Zhang as the co-first authors of the pap.
Using the laboratory's latest transgenic mice, the team found that AV specifically mediated the storage of working memory by specifically regulating different subregions of the anterior thalamus; with the aging of mice, working memory declined, accompanied by the anterior thalamus Decreased neuronal excitability; increasing the activity of this group of neurons using optogenetic methods can significantly improve working memory in aged mi.
In the article, the researchers used the T-maze test device to study the working memory function of mi.
Using C1ql2-Cre transgenic mice [11], the researchers used optogenetic methods to specifically inhibit different subregions of the anterior thalamus and found that AD was specifically involved in working memory encoding, AV was specifically involved in working memory storage, and specific inhibition was Neither AD nor AV affected information retrieval from working memo.
Furthermore, the Cal-light method was used to label neurons active in different periods of working memory, and it was found that the number of labeled AV neurons increased significantly during the storage period of working memo.
These results suggest an important role of AV neurons in the information storage period of working memory (F.
Figure 1 AV participates in the storage period of working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) The brain is a huge network, and the neural connections of various brain regions are intricately connect.
Next, scientists wanted to know how AV affects working memory through neural circui.
Previous studies have shown that AV can project to various regions outside the thalamus, such as the cortex and the infracerebral peduncle [1
Using optogenetic methods to inhibit different AV circuits, it was found that AV projections to the parasubiculum (PaS) were specifically involved in working memo.
Because PaS can project abundantly to the entorhinal cortex (EC), which is considered to be one of the most important learning and memory centers in the brain [13], the researchers reasoned that PaS neurons projecting to the EC could receive Neuronal regulation from .
We tested this hypothesis using neural circuit traci.
Meanwhile, optogenetic inhibition of the ATN→PaS→EC loop significantly affected the working memory function of mi.
Through the regulation of different loops, the researchers found the AV loop that plays a role in working memory (Figure
Figure 2 The AV→PaS loop is involved in the storage period of working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Since inhibiting the activity of AV neurons will damage working memory, increasing the activity of AV neurons can Does it enhance working memory in mice? Using the same optogenetic method, the researchers excited the AV neural circuit in different stages of working memory and found that light stimulation of the ATN→PaS circuit during the memory storage period can significantly improve the working memory of mice (F.
Figure 3 Exciting AV neurons can improve working memory (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Although some studies have revealed that abnormal frontal thalamic function is associated with reduced executive function in the elderly [4], the specific The mechanisms underlying the dysfunction of thalamic circuits in aging-related disorders have not been investigat.
The researchers first confirmed that working memory function in older mice declined significantly compared to younger mi.
Meanwhile, using brain slice electrophysiology, the researchers found that the activity of AV neurons was reduced in aged mi.
So, if artificially boosting the activity of this group of neurons can improve working memory in older mice? The answer is y.
Increasing the excitability of AV neurons or stimulating the ATNàPaS neural circuit can improve the working memory function of mi.
It is worth noting that the prefrontal cortex (PFC) is considered to be an important brain area for working memory [1
Exciting the PFC of old mice can also improve working memory in mice, but it improves anxiety-like behaviors in mice, which This "side effect" does not exist when the ATN→PaS neural circuit is excit.
These results suggest that the abnormality of working memory in aged mice can be improved by modulating AV neurons or AV neural circuits (F.
Figure 4 Regulation of AV neurons or neural circuits can improve working memory in aged mice (Source: Roy DS, Zhang Y, et .
, PNAS, 2022) Conclusions and discussions of the article, inspiration and prospects for this study combined with optogenetic methods The important role of the frontal thalamus in working memory was revealed, and it was found that the specific thalamic circuit ATN→PaS→EC (frontal thalamus→hemicephalic inferior peduncle→entorhinal cortex) was involved in the storage of working memo.
Modulating this circuit can improve working memory abnormalities in aged mice without affecting other behaviors of the mi.
Therefore, the anterior ventral region (AV) may be a potential brain region for the treatment of working memory abnormaliti.
We know that many diseases such as schizophrenia and Alzheimer's disease are accompanied by abnormal working memo.
Interestingly, scientists found a decrease in the number of frontal thalamic neurons in some brain samples from patients with schizophren.
Whether AV plays a role in schizophrenia or other disorders of working memory loss remains to be studi.
Researchers use optogenetic methods to regulate neuronal activity, but this method is currently difficult to apply clinical.
If the corresponding molecular targets can be found, the development of non-invasive therapeutic methods would be a meaningful breakthrough
Link to the original text: https://d.
org/11073/pn.
2118712119 In this article, postdoctoral fellows Dheeraj.
Roy and Zhang Ying are the co-first authors, and Professor Feng Guoping, Dheeraj.
Roy, and Zhang Ying are the co-corresponding autho.
Feng Guoping (left), Dheeraj.
Roy (middle), Zhang Ying (right) (photo courtesy of MIT Feng Guoping Laboratory) Talent Recruitment [1] "Logical Neuroscience" is looking for associate editor / editor / operation Post (online office) Selected articles from previous issues【1】Autophagy︱Ye Yihong’s research group reveals new molecular mechanism of neuronal ceroid lipofuscin deposition: DNAJC5/CSPα gene mutation leads to lysosomal homeostasis imbalance【2】J Neuroinflammation | Wang Yilong's team reports new evidence on the relationship between blood inflammatory markers and cerebral small vessel disease 【3】Science︱Neural mechanism of non-cued goal-directed behavior 【4】Front Psychiatry︱Yang Zhi group reports a state anxiety tracking model with high temporal resolution 【5】Review of Neural Regen Res︱The advantages of Rho kinase and its inhibitor Fasduil in the treatment of neurodegenerative diseases 【6】Nat Neurosci︱He Yanlin/Xu Yong team reported the new mechanism of anorexia nervosa 【7】Transl Psychiatry︱Wang Xueyi The team has made new progress in the study of the brain mechanism of the impact of early-life stress on cognitive function in adulthood【8】Nat Neurosci︱Song Juan’s team revealed that the hypothalamic circuit regulates hippocampal neurogenesis, promotes memory retrieval and fights anxiety-like behaviors【9】Mol Psychiatry︱ Shi Yun/Xu Zhengfeng/Yang Jianjun's team revealed a new mechanism of glutamate receptor mutation impairing cognition【10】Cereb Cortex︱Li Changqi's team revealed the role and mechanism of light-intensity exercise in promoting cued fear memory loss in mice [1] Symposium on Single-Cell Sequencing and Spatial Transcriptomic Data Analysis (Tencent Online Conference on June 11-12) [2] Seminar on Patch Clamp and Optogenetics and Calcium Imaging Technologies May 21-22 Tencent Conference Reference Literature (swipe up and down to read)Harada CN, Natelson Love MC, Triebel KL (2013) Normal cognitive agi.
Clin Geriatr Med 29:737-75 Murman DL (2015) The impact of age on cogniti.
Semin Hear 36:111 -12 Hughes EJ, et .
(2012) Regional changes in thalamic shape and volume with increasing a.
Neuroimage 63:1134-114 Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E (2007) Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging stu.
Am J Neuroradiol 28:226-23 Aggleton JP, Keith AB, Sahgal A (1991) Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in ra.
Behav Brain Res 44:151-16 Warburton EC, Aggleton JP (1999) Differential deficits in the Morris water maze following cytotoxic lesions of the anterior thalamus and fornix transecti.
Behav Brain Res 98:27-3 Mitchell AS, Dalrymple-Alford JC (2006) Lateral and anterior thalamic lesions impair independent memory syste.
Learn Mem 13:388-39 Savage LM, Hall JM,Vetreno RP (2011) Anterior thalamic lesions alter both hippocampal-dependent behavior and hippocampal acetylcholine release in the r.
Learn Mem 18:751-75 Winter SS, Clark BJ, Taube JS (2015) Disruption of the head cell direction network impairs the parahippocampal grid cell sign.
Science 347:870-871 Nelson AJD, Kinnavane L, Amin E, O'Mara SM, Aggleton JP (2020) Deconstructing the direct reciprocal hippocampal-anterior thalamic pathways for spatial learni.
J Neurosci 40:6978- 6991 Roy DS, et al (2021) Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease mode.
Neuron 109:2590-2601 Jankowski MM, et al (2013) The anterior thalamus provides a subcortical circuit supporting memory and spatial navigati.
Front Syst Neurosci 7:41 Yamamoto J, Suh J, Takeuchi D,Tonegawa S (2014) Successful execution of working memory linked to synchronized high-frequency gamma oscillatio.
Cell 157:845-851 Lara AH, Wallis JD (2015) The role of prefrontal cortex in working memory: A mini revi.
Front Syst Neurosci 9:17 End of this article
