lesion studies
- how they do this more recently?
5 uncertainties involved in lesion studies
recently: microinjections, activate small ensembles of neurons, micro-ablation with electicity, cooling probes.
- 5 uncertainy
lesion of correct area; en passant axons; lesion of facilitating area; reduction of blood supply; lesion of inhibiting area
electrical stimulation of NS
- revealed 3 aspects of CNS function
- few clinical examples
- 3 problems
- uncertanties in interpretation
- nerve conduction velocity; spinal cord reflexes; brain associating senses
- DBS, cochlear, vagus, phrenic nerve
- en passant, lesion facilitating or inhibiting area.
- e- stim doesnt activate natural firing patter. activate en passant or neuronal networks that facilitate/inhibit other networks. implanted electrodes are invasice.
TMS
- quick mechanism
advantages
disadvantages
- strong magnetic field pulse, induce electrical current = activate or inhibit neurons and brain function
+ Non-invasice; test spine during surgery; stundy interaction of spinal cord and corticospinal commands - spatial resolution is poor; low repitition rate; stimulates brain surface.
recording electrical activity of large numbers of neurons. = EEG
- advantages
- disadvantages
non-invasive; detect normal and abnormal activity; high temporal resoltuion, diagnose epilepsy, tumors stroke.
- low spatieal resolution
- monitors surface activity
recording small ensembles of neurons
- implants
- representation of area
- implant array is more stable
- array is more representative than single neuron
recording single neurons in slices
- method:
- advantage
- disadvantage
- electrical/optical recording from neuron in brain slice
(+): record identified neurons, net, or neural networks. visualize and patch clamp single neuron. high spatial and temporal; apply drugs, NT, blocker
(-): invasive, damage surrounding tissue, abolish normal inputs/outputs
fundamental discoveries- intracellular second messengers; minute quantity of drug causes change = major change in bodily function.
(+)
(-)
characterize neurons in neurotransmitter properties.
visualize neurons.
manipulate specific functions.
drug discover
may not reveal mechanism.
may affect many parts of CNS
neurogenetics - how genes = neural function mechanism: method advantages disadvantages
specific neuronal types turned on after neuron is born. specific genes turned on by transcription facts or factors/signals secretes
- specific genes knocked out. = developmental or behavioural change
(+): highly conserved from invertebrates to humans. genetic testing can confirm
(-): absence from birth = other CNS neurons take over function. behaviour - complex and variable.
optogenetics: insert genes that sensitize neurons to light
method:
(+):
(-)
gene codes for production of membrane channels sensitive to specific wavelengths of light \+: popln of specific types of neurons may be turned on or off. = sudden change in behaviour. clinical applications. -: induced neuronal firing could be abnormal, sub-class of targeted neurons may have conflicting functions
PET
- mechanism
- +
- -
activate neurons metabolize glucose.
FDG - radioactive glucose. taken in by active neuron, photon emission detected
+: noninvasice, detect deep brain activity, human research
-: isotope injection, low temporal & spatial, doesnt differentiate btw inhibitory & excitatory.
fMRI mechanism method BOLD \+ -
brain areas with active neurons have higher blood flow.
- line up to magnetic field. relaxing back to orginical state detected.
Blood oxygenation level dependent (BOLD)
+: noninvasive, detects local blood flow, better temporal resolution
-: blood flow =/= neuronal activity. neurons not primarily responsible for function, no distinction btw excite/inhibit. thresholding can be misleading
tensor diffusion MRI
-water
+
-
water along axons. allows white matter to be visualized
+: non-invasive, functional connectivity (w fmRI pair)
-: smae as fMRI, new technique
fluorescence of active neurons mechanism method \+ -
voltage and Ca fluctuate.
changes in reflectance of active neurons are detected through hole in skull - add sensitive dyes.
+: detect large area of brain. very good temporal, good spatial
-: invasive, surface layers only
mathematical modeling - neurocomputation
method:
+
-
set up computer model w software.
+: experiments impossible on live animals. desvribe system in precise math terms. predictions of behaviour
-: difficult to mathematically model, difficult to see where are correct, take lots of computing time.
