Dysfunction of Glutamate Delta-1 Receptor-Cerebellin 1 Trans-Synaptic Signaling in the Central Amygdala in Chronic Pain
Abstract
:1. Introduction
2. Material and Methods
2.1. Animals
2.2. Immunohistochemistry
2.3. Whole-Cell Electrophysiology
2.4. Synaptoneurosome Preparation and Western Blot Analysis
2.5. Stereotaxic Surgery
2.5.1. Stereotaxic AAV Injection
2.5.2. Cannulation
2.6. Pain Induction Models
2.6.1. CFA Inflammatory Pain Model
2.6.2. Spinal Nerve Ligation Pain Model
2.7. Drug Administration
2.7.1. Recombinant Cerebellin 1 (Cbln1) Administration
2.7.2. Chemogenetics
2.8. Behavioral Assessment Tests in Mouse
2.8.1. Von Frey Filament Test
2.8.2. Tail Flick Test
2.8.3. Hotplate Test
2.8.4. Gabapentin Induced Conditioned Place Preference
2.8.5. Formalin Test
2.8.6. Fear Conditioning
2.9. Behavioral Assessment Tests in Rats
2.9.1. Vocalization
2.9.2. Von Frey Test
2.9.3. Elevated plus Maze
2.10. Statistics
3. Results
3.1. Unique Cell- and Input-Specific Expression of GluD1 in the Central Amygdala
3.2. GluD1 Is Necessary for Normal Excitatory Neurotransmission at the Parabrachio-Amygdala Synapses
3.3. Downregulation of GluD1-Cbln1 in the CeLC in Inflammatory and Neuropathic Pain Models
3.4. Recombinant Cbln1 Rescues Mechanical Hypersensitivity in an Inflammatory Pain Model with a Unique Time Course
3.5. Recombinant Cbln1 Normalizes Synapse Structure in the CeLC in an Inflammatory Pain Model
3.6. Recombinant Cbln1 Mitigates Averse and Affective Behaviors in a Neuropathic Pain Model
3.7. Cbln1 Release in the Central Amygdala in Normal Animals may Serve as a Nociceptive Signal
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data availability statement
Acknowledgments
Conflicts of Interest
References
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Gandhi, P.J.; Gawande, D.Y.; Shelkar, G.P.; Gakare, S.G.; Kiritoshi, T.; Ji, G.; Misra, B.; Pavuluri, R.; Liu, J.; Neugebauer, V.; et al. Dysfunction of Glutamate Delta-1 Receptor-Cerebellin 1 Trans-Synaptic Signaling in the Central Amygdala in Chronic Pain. Cells 2021, 10, 2644. https://doi.org/10.3390/cells10102644
Gandhi PJ, Gawande DY, Shelkar GP, Gakare SG, Kiritoshi T, Ji G, Misra B, Pavuluri R, Liu J, Neugebauer V, et al. Dysfunction of Glutamate Delta-1 Receptor-Cerebellin 1 Trans-Synaptic Signaling in the Central Amygdala in Chronic Pain. Cells. 2021; 10(10):2644. https://doi.org/10.3390/cells10102644
Chicago/Turabian StyleGandhi, Pauravi J., Dinesh Y. Gawande, Gajanan P. Shelkar, Sukanya G. Gakare, Takaki Kiritoshi, Guangchen Ji, Bishal Misra, Ratnamala Pavuluri, Jinxu Liu, Volker Neugebauer, and et al. 2021. "Dysfunction of Glutamate Delta-1 Receptor-Cerebellin 1 Trans-Synaptic Signaling in the Central Amygdala in Chronic Pain" Cells 10, no. 10: 2644. https://doi.org/10.3390/cells10102644