Lecture 9- Measuring neural activity II

Question 1

How do you use genetically encoded Ca indicators? (GCaMPs)

Answer 1

-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

Question 2

What is the resolution like with genetically encoded Ca indicators?

Answer 2

-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!

Question 3

Are there equivalents of the GCaMPs for the brain?

Answer 3

-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

Question 4

What is at the other end of the spectrum?

Answer 4

-psychophysics -we’ve been talking about single cells, this is about the whole system

Question 5

What is the classic visual brightness illusion and what does it tell us about the nervous system?

Answer 5

-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

Question 6

What is the first element of psychophysics?

Answer 6

-structural imaging of brain

Question 7

What are the characteristics of an MRI (Magnetic Resonance Imaging)

Answer 7

-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)

Question 8

What is the resolution like in an MRI?

Answer 8

-very good spatial resolution and extremely poor temporal resolution

Question 9

What are the types of dynamic brain imaging?

Answer 9

-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

Question 10

What are the characteristics of fMRI?

Answer 10

– 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)

Question 11

What are the characteristics of PET?

Answer 11

– 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

Question 12

What is an example of fMRI usage (odours)?

Answer 12

• 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

Question 13

What is the resolution like for fMRI and PET?

Answer 13

• Low spatial resolution and often poor temporal resolution

Question 14

What are fMRI and PET good for and often used for?

Answer 14

• Good for non-invasive studies of locations of specific functions • Both used to localise brain regions associated with specific behaviours

Question 15

Is fMRI and PET resolution improving?

Answer 15

• 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

Question 16

What is the example of PET imaging (visual attention)?

Answer 16

• 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

Question 17

What does functional brain imaging of temporal lobe during face recognition tell us?

Answer 17

-there is a specific part of the brain dedicated to face recognition in the right temporal love

Question 18

What is MEG?

Answer 18

-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

Question 19

What are the weaknesses of MEG? (these broadly apply to fMRI, MRI and PET as well)

Answer 19

• 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

Question 20

What is a portable and non-invasive technique that allows us to overcome some of the weaknesses of the other techniques?

Answer 20

-Electroencephalography (EEG)

Question 21

What are the characteristics of EEG?

Answer 21

• 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

Question 22

What does the EEG measure?

Answer 22

• 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

Question 23

What was the example of EEG usage (dolphin)?

Answer 23

• 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

Question 24

How could you get higher spatial resolution?

Answer 24

• 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

Question 25

Need to know:

Answer 25

• Strengths and weaknesses of the 3 major brain imaging systems – MRI – PET – EEG • When these methods might be used • Essential controls