Guest lecture Flashcards
What are things to consider for your method of choice when performing neuronal experiments?
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
Phineas Gage impaled its own head on accident during work, which led to the pole damaging its frontal association cortex. Phineas his personality changed entirely (inability to function socially, inconsiderate, inability to plan).
This was studied (lesion studies) and was used to find functions of the frontal associations cortices.
Try to think of what methods are used here.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
The lesion study was observational, where a correlation was found between the damage and function of the frontal association cortices.
In patient H.M., his hippocampus was removed on both sides. It was found that he could not produce any new memories.
Try to think of what methods are used here.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
This study was interventional, where a correlation was found between the absence of the hippocampus and memory formation.
In fMRI studies about hippocampal function, they saw that when patients were navigating in a virtual world, the hippocampus became active.
Try to think of what methods are used here.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
fMRI studies are observational and invasive (due to the use of magnetic force). In this study, a correlation was found.
Dr Wilder Penfield described the functions of the sensory and motor cortex by opening up the skull and while patients were awake stimulating certain brain areas.
Try to think of what methods are used here.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
This study is of course interventional en invasive. Furthermore, (I think) in this study causations were found (stimulate a certain area of the brain, response in a certain area of the body).
Nowadays, a certain brain surgery is referred to as the Penfield condition/procedure. What does this mean?
Penfield condition → mapping of brain regions
Penfield developed a method where he would keep his patients awake and where the patients were able to interact with him. Using local anesthetics, he removed the skull cap to expose the brain tissue of the conscious patient.
The Penfield procedure also led to the idea of deep brain stimulation. What is this?
Basal ganglia good target for deep brain stimulation and motor control.
Deep brain stimulation is where an electrode is placed into a specific brain area. This electrode gets connected with a neurostimulator (or so called impuls generator) that gets place somewhere under the skin.
What brain area is a good target for solving problems with motor control, like during Parkinson’s Disease?
The basal ganglia
Try to think of what methods are used for deep brain stimulation.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
Deep brain stimulation → no cellular resolution, very high temporal resolution..
- Intervention
- Invasive
- Region
- No cellular resolution, very high temporal resolution.
Try to think of what methods are used in the cockroach experiment we did in this course..
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
- Invasive
- Observational
- Causational
Electrical recordings of neuronal activity were made during certain behaviors, like the visual representation of Jennifer Aniston. They found the Jennifer Aniston neurons that only spike when seeing the face of Jennifer Aniston (there are also grandmother neurons).
Note: this was done in epileptic patients whose brains were already being monitored for epileptic attacks.
Try to think of what methods are used here.
- Observation vs intervention
- Correlation vs causation
- Invasive vs non-invasive
- Whole brain, region, network or single neuron/synapse
- Spatial resolution, temporal resolution
- Intervention
- Causation (?)
- Invasive
- Single neuron
In epileptic patients, they can remove parts of the hippocampus to treat symptoms. In order to do this, surgeons need to cut away a piece of their temporal lobe. This can be used for research. What two questions are important for this research?
Do human neurons have special properties?
Do these properties relate to mental ability?
- Do human neurons have special properties?
- Do these properties relate to mental ability?
In epileptic patients, they can remove parts of the hippocampus to treat symptoms. In order to do this, surgeons need to cut away a piece of their temporal lobe. This can be used for research.
What can be said about the question if human neurons have special properties?
Human pyramidal neurons have large dendrites compared to other animals.
In epileptic patients, they can remove parts of the hippocampus to treat symptoms. In order to do this, surgeons need to cut away a piece of their temporal lobe. This can be used for research. With this, they also performed cognitive and mental tests (see picture).
What can be said about whether properties of neurons relate to mental ability?
It’s seen that:
- cortical thickness predicts dendrite length.
- cortical thickness positively correlates with IQ
- the speed of action potentials during repeated firing is faster in subjects with a high IQ
Note: these are correlational studies
Cortical thickness positively correlates with IQ
Cortical thickness predicts dendrite lenght
AP sped during repeated firing is faster in high IQ subjects
correlational observations by studying brain tissues and psychological measurements.
Historical view of techniques
What is optogenetics?
Many animals use light-sensitive ionchannels called rhodopsin channels. These animals use it for photosynthesis, or e.g. swimming towards the light.
Rhodopsin channels contain retinal, a light-sensitive organic molecule that catches photons and changes the shape of the channel.
Besides channelrhodopsin, there’s also halorhodopsin.
- Channelrhodopsin → conducts sodium and potassium and depolarizes the cell in the presence of blue light.
- Halorhodopsin → conducts CI- into the cell in the presence of blue light → makes the cell more hyperpolarized and thus silences the cell.
These two rhodopsins can be used in optogenetics, to activate or silence a cell.
What are motor loops and non-motor loops?
- Motor loops → the motor (premotor and somatosensory) cortex are connected to the brain areas of the basal ganglia (putamen, globus pallidus etc.). When a movement input signal is send from the motor cortex to the basal ganglia, the basal ganglia process it and the signal will come back to the motor cortex to initate the movement. This forms a (motor) loop.
- Non-motor loop → there are also loops that initiate certain behaviour that go through the basal ganglia and also come back to the cortex. These non-motor loops are especially responsible for the formation of habits (thus also addiction).
What role does the ventral tegmental area (VTA) play in addiction?
The VTA contains dopaminergic neurons that project to the striatum (part of basal ganglia). The VTA is sensitive to drugs like cocaine that activate these dopaminergic neurons to release dopamine. The increased release of dopamine affects the limbic loop (depicted in picture) and changes gene expression.
What is seen in the brain of a cocaine abuser?
Cocaine abuser → less dopamine since dopamine receptors are overly stimulated
Gene expression is altered and also the amount of dopamine receptor in the nucleus accumbens is drastically diminished (hence why during addiction, over time you need more of the same product to get the same effect).
A mouse is modified by optogenetic so that the ventral striatum of the mouse can be stimulated, when the light is turned on.
What is seen in the mouse that gets to choose to activate the laser by pressing a button?
That the optogenetic mouse chooses to activate the laser rather than pressing the working button that is not working.
Optogenetics can also be applied to the human brain. This was done in a patient with (partial) blindness. How was this done?
Rhodopsin acts similar like retinal photorecptors. Therefore, an adenovirus was used to transfect rhodopsin (ChR2) into the ganglion cells of the retina. Ganglion cells transmit the signals of rods and cones to the brain. So when light was sensed by these rhodopsins in the ganglion cells, the ganglion cells were activated and could send the signal to the brain. Light sensation was done with the use of light-stimulated goggles.
Measuring EEG at the same time —> light stimulation in ChR2 —> change activity in the cortex. Patients was able to grab objects and was aware of their surroundings.
Limitation —> highly invasive (virus, gene expression etc).
What were the conclusions of this experiment that is depicted in the picture?
- When measuring EEG during light stimulation of the rhodopsins in the ganglion cells of the blind person → activity of cortex changed.
- The patient was also able to grab objects and was aware of his surroundings.
What is a limitation of this experiment?
It’s highly invasive → virus, gene expression, optic fibers etc.
