DIANA fMRI reveals neural circuit changes due to thalamic dysfunction
Poster No:
1994
Submission Type:
Abstract Submission
Authors:
Semi Park1, Hyein Song2, Seung-Ah Oh3, Jae-Youn Keum1, Phan Tan Toi1, Heejung Chun2, Daehong Kim3, Jang-Yeon Park1,4
Institutions:
1Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Republic of Korea, 2College of Pharmacy, Yonsei University, Incheon, Republic of Korea, 3National Cancer Center, Goyang, Republic of Korea, 4Department of Biomedical Engineering Sungkyunkwan University, Suwon, Republic of Korea
First Author:
Semi Park
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Co-Author(s):
Jae-Youn Keum
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Phan Tan Toi
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University
Suwon, Republic of Korea
Jang-Yeon Park
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University|Department of Biomedical Engineering Sungkyunkwan University
Suwon, Republic of Korea|Suwon, Republic of Korea
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University|Department of Biomedical Engineering Sungkyunkwan University
Suwon, Republic of Korea|Suwon, Republic of Korea
Introduction:
In vivo direct imaging of neuronal activity (DIANA) has provided a breakthrough in brain science by enabling non-invasive dynamic investigation of neural circuits with millisecond precision (Toi et al., 2022; Keum et al.,2024). In this study, we used DIANA fMRI to investigate changes in neural circuits including the primary motor cortex (M1) when the ventromedial nucleus of the thalamus (VM) in mice was lesioned by inducing reactive astrocytes in the VM, which plays an important role in fine motor control (Starr & Summerhayes, 1983; Monconduit et al., 1999). Behavioral tests were also performed to determine if there were any changes in the voluntary movements of the mice.
Methods:
For DIANA fMRI, the VM-focal GiD model, Cre-inducible diphtheria toxin receptor transgenic mouse (n=8) was used. AAV-hGFAP-Cre-mCherry virus into VM was locally injected, followed by intraperitoneal injection of DT, to induce reactive astrocytes in VM. DIANA fMRI was performed twice, before and 1 week after DT injection, using a 7T animal scanner (BioSpec, Bruker). Ketamine/xylazine was used as an anesthetic. Electrical stimulation (1 ms duration, 0.5 mA) was applied to the right forepaw every 250 ms. A 1.5-min rest period was given every 5 trials to reduce neural adaptation. Time resolution was 5 ms and in-plane spatial resolution was 0.22x0.22 mm. Two slices were acquired (thickness, 1.5 mm): an anterior slice containing M1 and a posterior slice containing the thalamus. DIANA fMRI data were processed using spatiotemporal activation mapping (Keum et al., 2024) , which exploits temporal information of peak DIANA responses to identify regions of brain activation.
For behavioral tests , we used wild type mice (C57BL/6J, n=6) and injected Adeno-GFAP-GFP into the VM to induce reactive astrocytes. The open-field test (OFT) was performed in a square white acryl chamber. Each mouse was placed at the center of the chamber and allowed to move freely for 10 min. The total distance travelled was analyzed using open-source code written in MATLAB (MathWorks).
For behavioral tests , we used wild type mice (C57BL/6J, n=6) and injected Adeno-GFAP-GFP into the VM to induce reactive astrocytes. The open-field test (OFT) was performed in a square white acryl chamber. Each mouse was placed at the center of the chamber and allowed to move freely for 10 min. The total distance travelled was analyzed using open-source code written in MATLAB (MathWorks).
Results:
Spatiotemporal DIANA activation maps were presented with 5-ms temporal resolution. In DIANA fMRI, before DT injection, contralateral activation was observed in VM at 35 ms after stimulation, followed by M1 at 75 ms. However, after inducing reactive astrocytes, no activation was found in VM and M1, suggesting that reactive astrocytes suppressed VM activation and blocked neural signaling to M1. In the OFT, VM-damaged mice showed a reduced total distance traveled in an open field compared to control mice, indicating impaired motor function, which may be explained by the lack of DIANA activation in VM and M1 in DIANA fMRI. Although the difference was not statistically significant (p = 0.0662), these results suggest a trend toward decreased voluntary movement with VM lesion.
In addition, in DIANA fMRI, before VM lesion, activation of the hippocampal perforant pathway, known to be involved in sensory integration (Fones, 1993), was observed in the hippocampus. CA1 was activated at 65 ms (direct pathway), and activation in the entorhinal cortex (EC) was activated at 55 ms, followed by CA3 at 75 ms and CA1 at 95-100 ms (indirect pathway). The amygdala, known to be involved in emotional responses (Murray & Mishkin, 1985), was also activated at 30 ms. However, no activation was observed in the hippocampal perforant pathway after VM lesion. Amygdala activation was observed at 50 ms, after a 20 ms delay.
In addition, in DIANA fMRI, before VM lesion, activation of the hippocampal perforant pathway, known to be involved in sensory integration (Fones, 1993), was observed in the hippocampus. CA1 was activated at 65 ms (direct pathway), and activation in the entorhinal cortex (EC) was activated at 55 ms, followed by CA3 at 75 ms and CA1 at 95-100 ms (indirect pathway). The amygdala, known to be involved in emotional responses (Murray & Mishkin, 1985), was also activated at 30 ms. However, no activation was observed in the hippocampal perforant pathway after VM lesion. Amygdala activation was observed at 50 ms, after a 20 ms delay.
Conclusions:
In this study, DIANA fMRI revealed changes in neural circuits, i.e., no activation in VM and M1, after VM lesions, showing potential application as a biomarker for neurodegenerative diseases. Behavioral tests also confirmed that VM lesion decreased voluntary movements in mice by disrupting the relay of neural signal to the M1. In addition, delayed responses in the amygdala and lack of activation of the perforant pathway were observed after VM lesion, which requires further investigation through behavioral studies.
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Novel Imaging Acquisition Methods:
Non-BOLD fMRI 1
Keywords:
ANIMAL STUDIES
FUNCTIONAL MRI
HIGH FIELD MR
Motor
MRI
Sub-Cortical
Thalamus
Other - DIANA fMRI; Reactive astrocyte; Lesion
1|2Indicates the priority used for review
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2. Keum, J.-Y., Toi, P. T., Park, S., Chun, H., & Park, J.-Y. (2024). Direct imaging of neural activity reveals neural circuits via spatiotemporal activation mapping. bioRxiv.
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6. Murray, E. A., & Mishkin, M. (1985). Amygdalectomy impairs crossmodal association in monkeys. Science, 228(4699), 604–606