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The Potential of DREADDs: A Game-Changer in Neuroscientific Research

Published On 03/28/2024 2:42 PM

The Potential of DREADDs: A Game-Changer in Neuroscientific Research
 
In the realm of neuroscience, understanding the intricacies of brain function has long been a pursuit marked by challenges and complexities. However, recent advancements in technology have opened up new avenues of exploration, one of the most promising being chemogenetics. In this blog, we'll delve into the world of DREADDs, exploring how they work, their applications, and the potential they hold for revolutionizing our understanding of the brain.
 
Understanding DREADDs: A Brief Overview
DREADDs, also known as engineered G protein-coupled receptors (GPCRs), have transformed the landscape of neuroscience research. DREADDs are engineered by mutagenesis to respond exclusively to synthetic ligands rather than their natural ligand. These synthetic ligands do not naturally interact with endogenous receptors in the body, offering researchers unparalleled specificity and temporal control in modulating neural circuits. There are several types of DREADDs, each designed to either excite or inhibit neuronal activity.
  • Excitatory DREADDs (eDREADDs): These receptors, such as hM3Dq, are coupled to Gq proteins, which activate intracellular signaling pathways upon ligand binding, leading to neuronal depolarization and increased firing rates.
  • Inhibitory DREADDs (iDREADDs): Conversely, iDREADDs like hM4Di are coupled to Gi proteins, inhibiting neuronal activity upon ligand binding and leading to hyperpolarization and decreased firing rates.
GPCR-based chemogenetic approach started with allele specific engineered β-adrenergic receptors in 1991, and then to RASSL (receptors activated solely by synthetic ligand) in 1998. In 2007, DREADD was developed, whose endogenous ligand is acetylcholine, and the synthetic ligand is Clozapine N-oxide. Clozapine N-oxide is shown to have no pharmacologic activity at the native target (Sternson & Roth, 2014).
 
Applications of DREADDs in Neuroscience
The versatility of DREADDs has made them invaluable tools in elucidating the complexities of the brain. DREADD-based methods have been examined across various brain functions such as appetite regulation, reward processing, motor control, pain perception, and anxiety-related behaviors, showcasing their capacity to influence neural circuits and behavioral outcomes (Cho et al., 2020). Here are just a few ways in which DREADDs are transforming neuroscientific research:
  • Mapping Neural Circuits: By selectively expressing DREADDs in specific neuronal populations, researchers can dissect intricate neural circuits and uncover their functional connectivity. This allows for a deeper understanding of how different brain regions communicate and cooperate to generate behavior.
  • Investigating Disease Mechanisms: DREADDs offer a powerful platform for modeling and studying neurological disorders. In a paper by Roth (2016), the author discussed the therapeutic implications of DREADDs in treating conditions such as Parkinson's disease and epilepsy. By manipulating neuronal activity in animal models, researchers can gain valuable insights into disease mechanisms and explore novel therapeutic interventions.
  • Controlling Behavior: DREADDs enable researchers to manipulate behavior with unparalleled precision. By activating or inhibiting specific neural pathways, scientists can probe the causal relationship between neuronal activity and behavior, shedding light on the neural basis of cognition, emotion, and motivation.
  • Drug Discovery and Development: DREADDs hold immense potential for drug discovery and development. By screening compounds that selectively modulate DREADD activity, researchers can identify novel therapeutic agents with enhanced efficacy and fewer side effects.
 
Challenges and Future Directions
While DREADDs have revolutionized the field of neuroscience, they are not without limitations. Challenges such as off-target effects, ligand pharmacokinetics, receptor desensitization, and long-term stability need to be addressed to maximize their utility. Additionally, further research is needed to optimize long-term stability and cell-type specificity of DREADD. Achieving cell-type specificity in DREADD expression is essential for dissecting circuitry and understanding complex neural networks. Future directions could involve the development of cell-type-specific promoters or intersectional approaches to target specific neuronal populations more precisely.
Looking ahead, DREADDs hold immense potential for modeling and studying neurological disorders. While the promise of DREADDs is undeniable, their successful application relies on efficient delivery vectors such as adeno-associated viruses (AAVs) and lentiviruses. This is where Biohippo enters the picture, offering a comprehensive AAV and lentivirus packaging service to researchers worldwide. With Biohippo's AAV and lentivirus packaging service, researchers have the support they need to unlock the full potential of DREADDs and drive groundbreaking discoveries in neuroscience.
 
Are you designing your experiment? If you have any requisition or questions, you may email us at orders@biohippo.com.

 
Mfr No Product SKU Vector Name  Promoter  Receptor  Price ($)
PT-0049 BHV12400091 rAAV-CaMKIIa-hM3D(Gq)-mCherry-WPREs  CaMKIIa  hM3D(Gq)  531
PT-0525 BHV12400092 rAAV-CaMKIIa-hM3D(Gq)-EGFP-WPRE-hGH polyA  CaMKIIa  hM3D(Gq)  531
PT-1144 BHV12400406 rAAV-CaMKIIa -DIO-hM3D(Gq)-mCherry-WPRE-hGH polyA  CaMKIIa  hM3D(Gq)  531
PT-1580 BHV12400600 rAAV-CaMKIIa-DIO-hM3D(Gq)-EGFP-WPREs  CaMKIIa  hM3D(Gq)  531
PT-0019 BHV12400084 rAAV-hSyn-DIO-hM3D(Gq)-mCherry-WPRE-hGH polyA  hSyn  hM3D(Gq)  531
PT-0152 BHV12400085 rAAV-hSyn-hM3D(Gq)-EGFP-WPRE-hGH polyA  hSyn  hM3D(Gq)  531
PT-0891 BHV12400357 rAAV-hSyn-DIO-hM3D(Gq)-EGFP-WPREs  hSyn  hM3D(Gq)  531
PT-0042 BHV12400088 rAAV-EF1α-DIO-hM3D(Gq)-mCherry-WPREs  Ef1α  hM3D(Gq)  531
PT-0160 BHV12400089 rAAV-nEF1a-fDIO-hM3D(Gq)-EGFP-WPRE-hGH polyA  Ef1α  hM3D(Gq)  531
PT-0816 BHV12400090 rAAV-EF1α-DIO-hM3D(Gq)-EYFP-WPRE-hGH polyA  Ef1α  hM3D(Gq)  531
PT-0988 BHV12400617 rAAV-EF1a-DIO-hM3D(Gq)-EGFP-WPREs  Ef1α  hM3D(Gq)  531
PT-1040 BHV12400823 rAAV-EF1a-fDIO-hM3D(Gq)-EGFP-3XFlag-WPRE-hGH polyA  Ef1α  hM3D(Gq)  531
PT-0855 BHV12400392 rAAV-CAG-DIO-hM3D(Gq)-mCherry-WPRE-hGH polyA  CAG  hM3D(Gq)  531
PT-0294 BHV12400093 rAAV-CMV-DIO-hM3D(Gq)-mCherry-WPRE-hGH polyA  CMV  hM3D(Gq)  531
PT-1079 BHV12400822 rAAV-CMV-DIO-hM3D(Gq)-P2A-mCherry-hGH polyA  CMV  hM3D(Gq)  531
PT-0138 BHV12400087 rAAV-TRE-tight-hM3D(Gq)-mCherry-WPRE-hGH polyA  TRE3G  hM3D(Gq)  531
PT-1169 BHV12400410 rAAV-GfaABC1D-hM3D(Gq)-mCherry-WPRE-SV40 polyA  GfaABC1D  hM3D(Gq)  531
PT-0650 BHV12400095 rAAV-GfaABC1D-hM3D(Gq)-mCherry-SV40 polyA  GfaABC1D  hM3D(Gq)  531
PT-0489 BHV12400094 rAAV-VGAT1-hM3D(Gq)-mCherry-WPRE-hGH polyA  VGAT1  hM3D(Gq)  531
PT-1084 BHV12400360 rAAV-Dlx5/6-hM3D(Gq)-mCherry-WPRE-hGH polyA  Dlx5/6  hM3D(Gq)  531
PT-1058 BHV12400665 rAAV-mOXT-hM3D(Gq)-mCherry-WPRE-hGH polyA  mOXT  hM3D(Gq)  531
PT-1070 BHV12400711 rAAV-mOXT-DIO-hM3D(Gq)-mCherry-WPRE-hGH polyA  mOXT  hM3D(Gq)  531
PT-1578 BHV12400661 rAAV-CRH-DIO-hM3D(Gq)-EGFP-WPRE-hGH polyA  CRH  hM3D(Gq)  531
PT-1582 BHV12400818 rAAV-CRH-DIO-hM3D(Gq)-EGFP-WPREs  CRH  hM3D(Gq)  531
PT-0017 BHV12400066 rAAV-CaMKIIa-hM4D(Gi)-mCherry-WPRE-hGH polyA  CaMKIIa  hM4D(Gi)  531
PT-0524 BHV12400388 rAAV-CaMKIIa-hM4D(Gi)-EGFP-WPRE-hGH polyA  CaMKIIa  hM4D(Gi)  531
PT-1143 BHV12400405 rAAV-CaMKIIa-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  CaMKIIa  hM4D(Gi)  531
PT-0153 BHV12400069 rAAV-hSyn-hM4D(Gi)-EGFP-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0170 BHV12400070 rAAV-hSyn-fDIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0344 BHV12400071 rAAV-hSyn-DIO-hM4D(Gi)-EYFP-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0020 BHV12400068 rAAV-hSyn-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0170 BHV12400070 rAAV-hSyn-fDIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0344 BHV12400071 rAAV-hSyn-DIO-hM4D(Gi)-EYFP-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-1572 BHV12400514 rAAV-hSyn-Con Fon-hM4D(Gi)-EGFP-WPRE-hGH polyA  hSyn  hM4D(Gi)  531
PT-0159 BHV12400073 rAAV-nEF1α-fDIO-hM4D(Gi)-EGFP-WPRE-hGH polyA  Ef1α  hM4D(Gi)  531
PT-0815 BHV12400074 rAAV-EF1α-DIO-hM4D(Gi)-EYFP-WPREs  Ef1α  hM4D(Gi)  531
PT-0987 BHV12400395 rAAV-EF1α-DIO-hM4D(Gi)-EGFP-WPREs  Ef1α  hM4D(Gi)  531
PT-1039 BHV12400817 rAAV-EF1α-fDIO-hM4D(Gi)-EGFP-3XFlag-WPRE-hGH polyA  Ef1α  hM4D(Gi)  531
PT-0043 BHV12400072 rAAV-EF1α-DIO-hM4D(Gi)-mCherry-WPREs  Ef1α  hM4D(Gi)  531
PT-0856 BHV12400816 rAAV-CAG-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  CAG  hM4D(Gi)  531
PT-1080 BHV12400815 rAAV-CMV-DIO-hM4D(Gi)-P2A-mCherry-hGH polyA  CMV  hM4D(Gi)  531
PT-0312 BHV12400076 rAAV-TRE-tight-hM4D(Gi)-mCherry-WPRE-hGH polyA  TRE3G  hM4D(Gi)  531
PT-0036 BHV12400334 rAAV-TRE3g-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  TRE3G  hM4D(Gi)  531
PT-1091 BHV12400683 rAAV-GFAP-hM4D(Gi)-mCherry-WPREs  GFAP  hM4D(Gi)  531
PT-0488 BHV12400387 rAAV-VGAT1-hM4D(Gi)-mCherry-WPRE-hGH polyA  VGAT1  hM4D(Gi)  531
PT-0618 BHV12400390 rAAV-VGAT1-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  VGAT1  hM4D(Gi)  531
PT-1191 BHV12400412 rAAV-mDlx-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  mDlX  hM4D(Gi)  531
PT-0608 BHV12400077 rAAV-GAD67-DIO-hM4D(Gi)-mCherry-WPRE-hGH polyA  GAD67  hM4D(Gi)  531
PT-0300 BHV12400075 rAAV-PTH-hM4D(Gi)-mCherry-WPRE-hGH polyA  PTH  hM4D(Gi)  531
PT-0123 BHV12400083 rAAV-CaMKIIa-HA-KORD-IRES-mCitrine-WPRE-hGH polyA  CaMKIIa  KORD  531
PT-0122 BHV12400082 rAAV-hSyn-dF-HA-KORD-IRES-mCitrine-WPRE-hGH polyA  hSyn  KORD  531

References:
Atasoy D, Sternson SM. Chemogenetic Tools for Causal Cellular and Neuronal Biology. Physiol Rev. 2018 Jan 1;98(1):391-418. doi: 10.1152/physrev.00009.2017. PMID: 29351511; PMCID: PMC5866359.
Cho, J., Ryu, S., Lee, S. et al. Optimizing clozapine for chemogenetic neuromodulation of somatosensory cortex. Sci Rep 10, 6001 (2020). https://doi.org/10.1038/s41598-020-62923-x
Roth BL. DREADDs for Neuroscientists. Neuron. 2016 Feb 17;89(4):683-94. doi: 10.1016/j.neuron.2016.01.040. PMID: 26889809; PMCID: PMC4759656.
Sternson SM, Roth BL. Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci. 2014;37:387-407. doi: 10.1146/annurev-neuro-071013-014048. Epub 2014 Jun 16. PMID: 25002280.


 
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