During in vivo electrophysiological recordings in anesthetized rodents, the animals should be in a similar anesthetic state so that brain responses are comparable. However, some animals respond better or worse to anesthetic agents. Some physiological measures (heart beat, temperature, reflexes) can already give a clue to how the animal is responding. But are there any quantitative measures to assess the animal's brain state based on LFPs or cell responses? Studies show qualitative changes in the power spectrum depending on the brain state, but I haven't found any quantitative criteria.
This is a very tricky problem as the effects of different anaesthetics on EEG and other responses (down to cellular level) all vary, so comparing between agents is very difficult - within a single anaesthetic agent, then there are assorted measures that can be used, including the equivalent of BIS (although most of the animal data is in larger species, where a human-style electrode can be attached). This at least gives a "quantitative" measure.
It is a complex problem as stated above, but can be made simpler by controlling as many of environmental parameters as possible. Like human surgery, clearing the GI tract helps smooth and stablize metabolism. Size/age of the animals will help regulate variables, as does handling/taming of the animals. Once into the surgery, the timing and duration before the critical recordings begin to become standardized and occur in a similar time window, and monitoring and adjusting body/brain temperature.
Does it have to be acute surgical recordings? Can a chronic implantation be done, and then for the critical recordings the animals are anesthetized?
What are the exact recordings to be performed, is there data of this nature from awakebehaving animals, and from other anesthetized preps to compare to?
So having a favourite weight/age for the surgery and recordings will help. If there is an inhouse breeding program then using littermates in different groups is even better. Daily handling/ taming for a week also will reduce stress such that most animals will be at a "floor" level and more similar, than the individual differences at a maximal "ceiling" level that would occur with no handling whatsoever. Having the animals food deprived from the night before will clear the GI tract and even out anesthetic metabolism and therefore level. Initiating the recordings within a set time window will permit the duration and depth of the anesthetic and brain temperature to be less variant. Actively controlling the body temperature with a heating pad (that does not interfere with recordings) will also reduce variance.
On this last point we have shown changes in hippocampal evoked potentials under a variety of temperature manipulations, including swimming in cold water, sleep, simple behavioral activity increases, anesthetic, and radiant heating.
Cain, D.P., Hargreaves, E.L., and Boon, F. (1994). Brain temperature-and behavior-related changes in the dentate gyrus field potential during sleep, cold water immersion, radiant heating, and urethane anesthesia. Brain Research, 658, 135-144.
Downloadable in *.pdf from my website pageoneuroplasticity, under the "about Eric" tab, and subsequently downloadable reprints tab.
There are no two anesthetic agents that would produce exactly the same brain state unless given at a high dose that would completely suppress neuronal activity. You may wish to adjust the dose to achieve regular slow wave (delta) activity; with a certain class of general anesthetics (mostly GABAA acting agents) this may be attainable and the states will be relatively similar, although not identical. However, do not expect a close correspondence between brain state (EEG) and nociceptive reflexes across various agents.
Dear Claudia,
I do not know if my answer fits correctly to the goal of your experiments, but the in vivo imaging techniques could furnish a quantitative information about the brain function. Such imaging techniques include either functional MRI or FDG-PET scans.
Kind regards,
Carmen
Thank you for your replies. To clarify, the goal of my experiments is not to compare between different anesthetic agents. I use isoflurane to lightly anesthetize my subjects, I apply sensory stimuli and I measure neural responses. I would like to minimize variability in the brain responses during the anesthesia (although strictly speaking, there is also a lot of variability when recording in awake animals because some might be more sleepy and less alert than others).
It is very important to control environmental parameters, and I can try to better control some of the variables mentioned by Eric Hargreaves (thank you for that useful summary).
One of the measures for monitoring anesthetic depth is the EEG. As pointed out by Anthony Hudetz, it can be useful to look online for a certain activity pattern (e.g. delta waves). My question is whether it is possible to use the EEG power spectrum to assess anesthetic depth (or brain state) - rather than assessing it just by looking at the data. A study that describes changes in power spectra in non-anesthetized mice under different sleep/wake conditions has been published by Bessaih et al., Epilepsia, 53(8):1429–1435, 2012. I'm looking for similar information on anesthetized animals.
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