Rho GTPases in the Amygdala—A Switch for Fears?
Abstract
:1. Introduction
2. The Amygdala Is the Fear Center in the Brain
3. Rho GTPases and Their Regulation
4. Rho GTPases in Synaptic Spine Plasticity
5. Rho GTPases and Fear Conditioning in the Amygdala
6. The Critical Role of Rich2 in Fear Modulation
6.1. Rich2 Deletion Induces Specific Behavioral Changes in Mice
6.2. Rich2 Deactivates Different Rho GTPases in Different Brain Regions
6.3. Spine Morphology in Rich2 Knock-Out Animals
6.4. Deletion of Rich2 Affects the Immediate-Early Gene Expression in the Amygdala
6.5. Shank3-Rich2 Interaction in the Context of Fear Learning
7. Rho GTPases and Fear Modulation in Neurological/Neuropsychiatric Disorders with Anxiety and Phobia as Comorbidities
7.1. Rho GTPases in Mood Disorders
7.2. Rho GTPases in Autism Spectrum Disorders
7.3. Rho GTPases in Schizophrenia (SCZ)
7.4. Rho GTPases in Intellectual Disability (ID)
8. Rho GTPases as a Potential Drug Target
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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GTPase | Study Model | Study Findings | Ref. |
---|---|---|---|
RhoA | Neuronal culture | Inhibits dendritic growth and dynamics; constitutive overexpression leads to spine loss | [48] |
Rac1 | Neuronal culture | Promotes dendritic growth and dynamics | [48] |
Hippocampal slice culture | Overexpression of dominant-negative Rac1 reduces spine density | [49] | |
Conditional knock-out (alpha CaMKII promoter, deletion in the postnatal hippocampus) | Reduction in Rac1 activity and spine density, impairment in learning and memory (using Rac1 inhibitors) | [50,51] | |
Cdc42 | Neuronal culture | Promotes dendritic growth and dynamics | [48] |
Conditional knock-out (alpha CaMKII promoter, deletion in postnatal forebrain) | Spine density of hippocampal CA1 reduced, remote memory recall was impaired | [52] |
GTPase | BLA Expression | CEA Expression | Ref. |
---|---|---|---|
RhoA | + (in all parts of the amygdala) | [67] | |
Rac1 | + | not reported | [74,77] |
Cdc42 | + * | - | |
Kalirin | + | CEl and CEm | [78] |
Rich2 | + | [79] | |
BCR | + * | [80] | |
Dock9 | + * | [80] | |
Trio | + * | [80] | |
Wfs1 | + | [81] | |
Auts2 | + * | [80] | |
Dock4 | + * | [80] | |
RICS | + | [82] | |
RAPGEF6 | + | [83] | |
Oligophrenin 1 | ubiquitous (whole brain) | [84] | |
MEGAP | + | [85] |
GTPase/Regulator | Function in Amygdala | Association with Disease | Ref. |
---|---|---|---|
Rac1 | Extinction of contextual fear | [71] | |
Reconsolidation of auditory fear memory | [73] | ||
Post-training activation is required for both long-term and short-term auditory fear memory. | [74] | ||
Photoactivation of Rac1 in LA impairs fear memory. | [75] | ||
Alpha2- chimaerin (RhoGAP) | Abnormal contextual fear learning | [145] | |
ArhGAP4 | Odor stimulus avoidance | [65] | |
MEGAP (ArhGAP14) | Loss of MEGAP disrupts learning and memory | ASD and ID | [143] |
ArhGAP32 | Knock-out showed abnormal fear learning memory and ASD-like behaviors | ASD | [129,130] |
Oligophrenin 1 (RhoGAP) | Deletion leads to a deficit in fear memory extinction and alteration in the cAMP/PKA pathway | ASD, ID, and Cerebellar Hypoplasia | [134,135,139] |
RhoGEF KIAA0377 | Odor stimulus avoidance | [65] | |
Wfs1 | Modulation of anxiety and fear | Bipolar disease (Wolfram disease) | [146] |
TRIO (RhoGEF) | Neural Development | Bipolar disease | [115,147] |
Collybistin (ArhGEF9) | Deletion leads to loss of inhibitory neurons | ID, Anxiety, Epilepsy | [131] |
ArhGEF10 | Knock-out increased norepinephrine and serotonin levels in the amygdala | ASD | [118] |
RAPGEF6 | Deletion leads to reduced fear learning and less neuronal activation | SCZ | [83] |
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Sarowar, T.; Grabrucker, A.M. Rho GTPases in the Amygdala—A Switch for Fears? Cells 2020, 9, 1972. https://doi.org/10.3390/cells9091972
Sarowar T, Grabrucker AM. Rho GTPases in the Amygdala—A Switch for Fears? Cells. 2020; 9(9):1972. https://doi.org/10.3390/cells9091972
Chicago/Turabian StyleSarowar, Tasnuva, and Andreas M. Grabrucker. 2020. "Rho GTPases in the Amygdala—A Switch for Fears?" Cells 9, no. 9: 1972. https://doi.org/10.3390/cells9091972