Optogenetics and meditation Flashcards
What was the hypothesis tested by Weible and colleagues in 2017?
What functions are associated with Anterior cingulate cortex (ACC)?
What is promoter?
In a nutshell, the technique involves putting together a genetic construct where a promoter- that is a region of the DNA where the transcription of a certain gene starts- will be added just before the sequence of our gene of interest. This promoter will have the same sequence of the promoter of the gene that encodes a certain protein we want to condition our construct to be active with.
What steps are taken to use optogenetics in a mouse?
The construct is then inserted into a virus which is injected into the mouse brain. It will infect many cells, but as we’ve said, the expression of our sensitive to light proteins will only occur in neurons that express the protein whose promoter region in the DNA is similar to that of the promoter of our construct.
So, in the brain of mice injected with the virus carrying the construct of the sensitive to light protein, only neurons expressing the gene for parvalbumin, that is, only interneurons, will express our special proteins. A fibre optic cable will then be implanted into the mouse brain, and every time the appropriate wavelength of light is delivered, our special ion channels or protein pumps will become activated.
What channels are affected? How?
How can anxiety like behaviour in rodentes be tested?
By using behavioural tests that have been validated to measure this specifc type of behaviour. Examples would be the elevated plus-maze test and the lightdark box.
What was the study design?
The authors used optogenetic control of interneurons, which are cells that express a protein called parvalbumin. So, their optogenetic construct was made in a way that in some animals only cells expressing parvalbumin – that is, only interneurons – would express channelrhodopsin 2 (ChR2) whereas in other animals, interneurons would express a light-driven ion pump called archaerhodopsin (Arch). It’s also important to remember that interneurons are GABAergic, inhibitory neurons which can very efectively inhibit excitatory pyramidal neurons. So, the authors used ChR2 to excite ACC interneurons (therefore leading to an overall decrease in activity in the ACC, as interneurons are inhibitory neurons) and Arch which will then inhibit interneurons in the ACC, leading to an increased global neuronal activity of excitatory pyramidal neurons in this area of the mouse brain. For 4 weeks, twenty thirty-minute sessions of light induced rhythmic activity in the ACC of mice randomly allocated to one of the following groups: 1) Receiving the light pulses at 1 Hz 2)At 8 Hz 3)At 40 Hz 4)No-laser They then checked 1) whether their optogenetic system worked, and 2) what the efect of inducing activation of the ACC by light pulses on specifc behaviours and measures that are indicative of anxiety, motor output and cognitive performance was. Behaviour was assessed before and after the 4-week stimulation.
What were the limitations of the study?
- We should not take the results on the anxiety measures as conclusive, considering that animals were tested only in one behavioural paradigm – the light/dark box;
- Little can be said about how the induction of rhythmic oscillations in the ACC actually relates to decreased anxiety-related behaviour. There is an association but we cannot say it is causal. The authors discuss the possibility of cortical stimulation leading to increased myelination and therefore to a more efcient regulation of limbic regions known to activate anxiety/fear responses, like the amygdala. • Finally, one important limitation of the study, is the fact that one of the controls used – the PV-PV line – exhibited diferences in motor output which could have been due to an efect of laser. In the context of the other fndings, this does not mean that we should disregard the study altogether. Nevertheless, just as we’ve seen in the podcast about mindfulness studies in humans, an overexcitement should be avoided, and future studies should make sure to advance the feld by refning even more the techniques and design used so that more conclusive answers can be drawn from the study.
