BL‐OG: BioLuminescent‐OptoGenetics

Moore, Christopher I.; Berglund, Ken

doi:10.1002/jnr.24575

Cited by 7 publications

(7 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To directly address the question of whether early life alterations in pyramidal activity can induce adult phenotypes and related circuit changes, we systematically enhanced pan-neocortical pyramidal activity levels in early development in healthy mice using BioLuminescent-OptoGenetic (BL-OG)-mediated chemogenetics (Berglund et al, 2013(Berglund et al, , 2016Moore and Berglund, 2019) to activate Emx1-positive neurons. We contrasted this activation with parallel activation of all neurons expressing the dopamine transporter (DAT), parvalbumin (Pvalb), or Dlx5/6.…”

Section: Introductionmentioning

confidence: 99%

Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

Medendorp

Pal

Waddell

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

In leading models of Autism Spectrum Disorder, and in human data, the efficacy of outgoing cortical connectivity transitions from overly exuberant to languid from early development to adulthood. This transition begs the question of whether the early enhancement in excitation might be a common driver, across etiologies, of these symptoms. We directly tested this concept by chemogenetically driving neuronal activity in neocortical neurons during postnatal days 4-14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons, impaired recruitment of inhibitory neurons and reduced cortico-striatal communication. These results directly support the prediction that changed firing in developing circuits irreversibly alters adult circuit function that leads to maladaptive changes in behaviors. This experimental approach offers a valuable platform to study the impact of disruption of developmental neural activity on the formation and function of adult neural circuits and behavior.

show abstract

Section: Introductionmentioning

confidence: 99%

Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

Medendorp

Pal

Waddell

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“… 5 and 6 ) integrates opto- and chemogenetic features in a single actuator. 7 With bioluminescent optogenetics (BL-OG), chemogenetic modulation of neural activity is achieved via delivery of a substrate, coelenterazine (CTZ), that is oxidized by the luciferase in the LMO, producing photons immediately adjacent to (within the same molecule) the optogenetic actuator. This approach allows the use of the same molecule for chemo- and optogenetic control at distinct times in the same animal or individually.…”

Section: Introductionmentioning

confidence: 99%

“…To combine the strengths of above techniques and increase user flexibility, we have developed a bimodal strategy in which a luciferase-opsin fusion molecule (a luminopsin, LMO; Refs. 5 and 6) integrates opto- and chemogenetic features in a single actuator 7 . With bioluminescent optogenetics (BL-OG), chemogenetic modulation of neural activity is achieved via delivery of a substrate, coelenterazine (CTZ), that is oxidized by the luciferase in the LMO, producing photons immediately adjacent to (within the same molecule) the optogenetic actuator.…”

Section: Introductionmentioning

confidence: 99%

Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence

Björefeldt,

Murphy,

Crespo

et al. 2024

Neurophoton.

Self Cite

View full text Add to dashboard Cite

. Significance Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. Approach We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). Results A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo , and efficient modulation of behavior. Conclusions We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.

show abstract

“…In comparison, chemogenetic approaches, including most notably designer receptors exclusively activated by designer drugs, DREADDs, provide sustained and minimally invasive modulation of neural populations distributed across much larger areas of the brain or body [3,4]. To combine the strengths of above techniques and increase user flexibility, we have developed a bimodal strategy in which a luciferase-opsin fusion molecule (a luminopsin, LMO; Berglund et al, 2013;Berglund et al, 2016) integrates opto-and chemogenetic features in a single actuator [5]. With BL-OG, chemogenetic modulation of neural activity is achieved via delivery of a substrate, coelenterazine (CTZ), that is oxidized by the luciferase in the LMO, producing photons immediately adjacent to (within the same molecule) the optogenetic actuator.…”

Section: Introductionmentioning

confidence: 99%

A New Highly Efficient Molecule for Both Optogenetic and Chemogenetic Control Driven by FRET Amplification of BioLuminescence

Björefeldt

Murphy

Crespo

et al. 2023

Preprint

View full text Add to dashboard Cite

The ability to manipulate neuronal activity both opto- and chemogenetically with a single actuator molecule presents unique and flexible means to study neural circuit function. We previously developed methodology to enable such bimodal control using fusion molecules called luminopsins (LMOs), where a channelrhodopsin actuator can be activated using either physical (LED driven) or biological (bioluminescent) light. While activation of LMOs using bioluminescence has previously allowed manipulation of circuits and behavior in mice, further improvement would advance the utility of this technique. Thus, we here aimed to increase the efficiency of bioluminescent activation of channelrhodopsins by development of novel FRET-probes with bright and spectrally matched emission tailored to Volvox channelrhodopsin 1 (VChR1). We find that pairing of a molecularly evolved Oplophorus luciferase variant with mNeonGreen significantly improves the efficacy of bioluminescent activation when tethered to VChR1 (construct named LMO7) as compared to previous and other newly generated LMO variants. We proceed to extensively benchmark LMO7 against previous LMO standard (LMO3) and find that LMO7 outperforms LMO3 in the ability to drive bioluminescent activation of VChR1 both in vitro and in vivo, and efficiently modulates animal behavior following intraperitonial injection of fluorofurimazine. In conclusion, we demonstrate a rationale for improving bioluminescent activation of optogenetic actuators using a tailored molecular engineering approach and provide a new tool to bimodally manipulate neuronal activity with increased bioluminescence-driven efficacy.

show abstract

BL‐OG: BioLuminescent‐OptoGenetics

Cited by 7 publications

References 6 publications

Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence

A New Highly Efficient Molecule for Both Optogenetic and Chemogenetic Control Driven by FRET Amplification of BioLuminescence

Contact Info

Product

Resources

About