Lecture 9- Measuring neural activity II Flashcards
How do you use genetically encoded Ca indicators? (GCaMPs)
-can use it to image a whole network of neurons in the gut wall -genetically engineer a mouse, where all cells expressing a protein can be made to a GCaMP (Ca indicator) -cross of a mouse expressing Cri and GCaMP3 -GCaMP3 is in all neural crest derivatives -so indicator only expressed in the cells controlling the gut -activation of nicotinic acetylcholine receptors
What is the resolution like with genetically encoded Ca indicators?
-high spatial width of field, low temporal resolution -calcium signal lasts a very long time -as Ca handling not happening instantaneously= slower than AP, the start of Ca means neuron is active but the decay of Ca is slow = in terms of resolution= indication when things start= spatial resolution high but temporal bad!
Are there equivalents of the GCaMPs for the brain?
-similar version for the brain as well= another inidcator that is event better -opening skull and exposing to virus so they have the indicator= then look at activity of neurons through the window of the skull, requires genetic engineering and much equipment -can record from a number of neural cells
What is at the other end of the spectrum?
-psychophysics -we’ve been talking about single cells, this is about the whole system
What is the classic visual brightness illusion and what does it tell us about the nervous system?
-which rectangle is the brightest -this is the psychopsychotic recording: -A) identical, the black background makes one look much lighter B) the same issue = this tells us about how the visual system work, on/off, our brain adjust our ability to determine colour in contrast to background -using this trick can work out how the system actually processes information -eyes detect green/red, blue/yellow, separately • Can use this and other illusions to study visual pathways via brain imaging • Psychophysics and other psychological tests need to be rigorous and well controlled
What is the first element of psychophysics?
-structural imaging of brain
What are the characteristics of an MRI (Magnetic Resonance Imaging)
-structural magnetic resonance imaging -very common, non-invasive -nucleus has characteristic response in a strong magnetic field and when it is changed, method that has been around for at least 50 years -recently= if computing plus tomography= can do MRI= depends upon having a huge magnet= shifting the magnetic field and measuring the consequences= can get beautiful images of particular regions, grey matter= lighter, white matter= darker -can tell if there is a disturbance= tumour (white) -the green, red etc= activity (from fMRI)
What is the resolution like in an MRI?
-very good spatial resolution and extremely poor temporal resolution
What are the types of dynamic brain imaging?
-fMRI -PET -• Both assume that increased blood flow reflects increased neural activity – Inherently limits time resolution -dynamic= where you look at the change in the brain during a function of some kind
What are the characteristics of fMRI?
– Usual form measures changes in blood oxygen levels (BOLD) – Also various forms of MR spectroscopy – Reasonable spatial resolution, but requires many repetitions – Used together with structural MRI -fMRI= if you repeat a stimulus and scan eventually can see the activity -instead of tuning to the mag. resonance to detect water (MRI) they detect BOLD (fMRI)
What are the characteristics of PET?
– Simplest form measures blood flow – Low spatial resolution -PET= inject radioactive marker, often tecticium (half life 90 mins),it is giving out the positron= flies a certain distance from a nucleus then hits electron= anihilation= 2 gamma rays going in opposite direction, from that you can tell where the positron was emitted Positron emission tomography= can label individual neurotransmitters etc. -300 different ligands that can be studied this way -the amount of radiation is tiny and not a health risk
What is an example of fMRI usage (odours)?
- fMRI of active regions to different odours
- allows you to see a key feature of the technique: same individual exposed to pleasant vs unpleasant odour -different pattern of activation
- the white circled= not related to odour per say, it has a role in the pleasantness
- pink= region lights up in both cases so must be connected to odour itself
- problems= the test subject must tell you they detect the signal= must move or something, must have output to the experimenter and that will have parts of the brain light up
What is the resolution like for fMRI and PET?
• Low spatial resolution and often poor temporal resolution
What are fMRI and PET good for and often used for?
• Good for non-invasive studies of locations of specific functions • Both used to localise brain regions associated with specific behaviours
Is fMRI and PET resolution improving?
• Resolution of fMRI is improving, but theoretical limits make it difficult to identify basic mechanisms • PET can be used to study binding sites for drugs and transmitters, but inherent limitations in spatial resolution limit its utility -both BOLD and PET= depend on the idea when neural activity increases then blood to that region increases, increase in BOLD= is the overcompensation for the loss of oxygen when active -these are delayed from the actual neural activity -limit to temporal resolution -nor fMRI or PET cannot replace single unit recordings etc. in terms of resolution temporally and spatial as well but can scan the whole brain -with PET= need cyclotron under the PET scan as the radioactive material decays very quickly
What is the example of PET imaging (visual attention)?
- right side responds to both fields, that is probably since the reporting needs that region
- this occupies about 10% of the cortex, also doesn’t give you a good structural resolution so must superimpose it on an MRI
What does functional brain imaging of temporal lobe during face recognition tell us?
-there is a specific part of the brain dedicated to face recognition in the right temporal love
What is MEG?
-magnetoencephalography (MEG) - a functional neuroimaging technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using very sensitive magnetometers. -MEG= magnetencelaphography -changing of electric field (always change in magnetic field) -millisecond temporal resolution -and good spatial -the problem is to filter the magnetic field of the world -things involved= the detectors are several tonnes in weight= cannot do experiments on moving subjects as too heavy! cannot use a freely behaving animals -head must be held extremely stationary -as signals go tissues move= anoteh spatial resolution limit on all these techniques
What are the weaknesses of MEG? (these broadly apply to fMRI, MRI and PET as well)
• Cannot be used with freely behaving animal • Spatial resolution too coarse to identify elements of neural circuits within an active region • Temporal resolution too slow to follow action potential activity • Requires very careful controls to discriminate activity of interest
What is a portable and non-invasive technique that allows us to overcome some of the weaknesses of the other techniques?
-Electroencephalography (EEG)
What are the characteristics of EEG?
• Electrical recording from the scalp • Usually use many recording electrodes • Can be used with moving subjects unlike other imaging methods • Excellent temporal resolution -electrodes on the scalp -millisecond resolution= 10s of millisecond= way better temporally than all except maybe MEG
What does the EEG measure?
- Electrode measures current produced in cortical dendrites by synaptic inputs
- Signal filtered by tissues of scalp and surrounding neural tissue
- Signal is sum of many currents, big signals - many synapses are active simulataneously
- Spatial resolution is very poor
- Responses to repeated stimuli can be averaged to obtain event related potentials
- Equivalent to fMRI averaging
- EEG measures= the synaptic currents that are being generated in the cortex
- in the pia matter
- telling you specifically about cortical activity
- so signal must be summed to be detected= so have lot of cells activated together
- the spatial resolution is bad because you need summation
- to get a good signal must repeat and repeat
What was the example of EEG usage (dolphin)?
• Dolphins sleep with only half their brain at a time • EEG from several sites shows slow wave sleep on left side and wakefulness on right • Note,highactivity during wakefulness leads to small noisy record -need to come up to the surface to get air -sleep pattern, thalamus and cortex= synchronise their activity and have higher waves -all the thalamic neurons start firing together and cortex as well= slow wave sleep -the summation doesn’t happen when awake as much, so noisy small wave signals
How could you get higher spatial resolution?
• Have to go inside the skull and use electrodes that sample only a small region – When sample many neurons – field potential (local EEG) – Smaller electrodes need to be close to neurons to record from them, but can record individual action potentials from several neurons at once • Can use arrays of electrodes to sample from a wider range of neurons • Works well in lab animals in vivo, including in awake, freely behaving animals -if want better spatial= need to go in to the skull, can leave electrodes in for a while (weeks), invasive but better -also need computer simulation and modelling so you can predict -can use in freely behaviouring animals, -need to kill the animal to see where the electrodes were
Need to know:
• Strengths and weaknesses of the 3 major brain imaging systems – MRI – PET – EEG • When these methods might be used • Essential controls
