NERVOUS SYSTEM - LECTURE 4 Flashcards
Recap of the sensory and motor cortex
We have an area called the primary motor cortex which is an area of very large neurons that are the upper motor neurons that are going to activate a neuron in the spinal chord and then activate another to active a muscle
There is an area anterior to the motor cortex that is responsible for planning motor movement - there is an activator/executor of motor activity, and an area for planning
Describe the humuncular representations in the motor vs sensory cortex
Within the primary motor cortex, there is a homoncular representation as shown in the diagram above and to the left. It represents the areas within which muscles would be effected f we activated those neurons
Importantly, the motor humunculus of the primary motor cortex si remarkably similar to the primary sensory cortex (there are some subtle differences)
In addition, a key feature of the humuncular representations is that there is a large representation of the face and hand, but everything else is relatively small. This shows that the face and hands have the most precise control
This is why we can articulate, smile and communicate with our face, and why our hand can write letters
Note that the representation represents the number of neurons and the level of precision necessary
Describe the pyramidal neurons
Pyramidal neurons (cells that have a large and pryamidal cell body located in the primary motor complex), are upper motor neurons that are the biggest neurons in the body (they are 160 microns across, while most cell bodies are 10-20 microns across).
They need to be big in order to store the energy to drive this activity
Describe the corticospinal tract
Pyramidal cell fibres in the primary motor cortex go down through the structure that is the internal capsule, and they will go more specifically towards the front/anterior as it passes through the midbrain.
Once it gets to the pons it will break up into smaller units (for practically sake as there are so many neurons in the pons).
Then they pass through the medulla, and within the medulla they begin to form a structure called the pyramidal decussation (they cross over to other side). As the neurons decussate, they form a cross (as both sides decussate to the other side), which also looks triangular and is referred to as pyramidal (another reason for its name).
Importantly, 85% of the fibres decussate to the other side. While 15% stay on the same side and only decussate at the spinals segmental level.
As mentioned in the previous lecture, they cross over into an area called the lateral funiculi or motor columns, and finally, when they reach the individual spinal segmental level where they will exit through the ventral root, the fibre in the motor column synapse/connects to a neuron in the motor column lamina/lower motor neuron pool (ON THE SAME SIDE), and then the upper motor neuron ends and the low motor neuron begins - it goes out through the ventral root to the muscle to activate it
Why do only some of the pyramidal fibres decusate at the medulla
The reason why - or at least the general belief why - there are some that cross in the medulla and some that don’t, is that the fribres that remain on the same side control axial muscles (big course muscle that generally localised the body where it needs to be localised), while those that cross over are responsible for the more refined movements (e.g. the movement of you arms and limbs, but not the large course movement of the trunk)
Describe spastic paralysis
If we end up with damage to the spinal chord that is localised in the pons, the upper motor neurons apply a high level of cerebral control over the lower motor neurons, but some of the lower motor neuron are independent of the upper motor neurons - which are involved in reflex action.
This means that the myotactic reflex can occur independent of the upper motor neuron.
However what tends to happen if you leave the reflex to occur without upper motor neuron control, the muscle will continue to get more tighter.
For this reason, this lesion causes spasticity/spastic paralysis - because the lower motor neurons can still do their job, but have too much control leading to stiff and rigid muscle
Describe how to test for spastic paralysis
One way to identify spasticity is to grab their hand, pull it down a little bit, and let it go - if reflexes are normal, the hand will com back a short way before stopping, but with spasticity, the reflex will be overexaggerated
Furthermore, if you cross you legs and tap the patella tendon, with spasticity it would be an exaggerated reflex and you would step aside
Describe flaccid paralysis
The alternative to spasticity is when we have damage to the lower motor neuron (damage in the spinal cord or elsewhere to the neurons)
This is a different problem because there is input form the upper motor neuron but no activity in the lower motor neuron
We refer to this as a flaccid paralysis - there is no neural control whatsoever (think of meat at the butcher shop)
Describe subcortical grey matter
Subcortical grey matter is the grey matter in the brain that is underneath the grey matter that makes up the cerebral cortex. It has a large number of grey volumes (large number of cell bodies)
The largest group of subcortical grey matter is a group called the basal ganglia
Describe the function of the basal ganglia
The basal ganglia is responsible for conveying mood through movement, and is required for refined movement control for slow and controlled movement
Part of the basal ganglia circutary has very distinct neurochemistry
First of all, the entire purpose of having basal ganglia circulatory is to activate exactly the right upper motor neurons.
If it is activated correctly, it will go down the path described earlier (go down to the medulla and then pyramidal decussates etc.)
The principal of how the basal ganglia works is that we have fibers from the premotor cortex/planning part of the cortex that send their connection down into the basal ganglia, which ultimately send other fibres back to the primary motor cortex to activate the correct muscles
Describe the function fo the cerebullum
The cerebellum (only shortly mentioned), sits at the brack of the brain and is responsible for extremely fast movement (ballistic movement)
With practice, over the time you can train the basal ganglia such that you can follow the movement and adjust things as you go to do things in a fast but practiced and learned way
As such most movement we use as humans relate to the basal ganglia - handwriting is a good example
Descrube the sturcute of the basal ganglia
There are 5 structures of the basal ganglia, we have:
1) In the wall of the lateral ventricle (a fluid filled space) is the caudate nucleus.
2) The caudate nucleus is linked to a structure called the putamen
Although they seem like two completely distinct regions, it is very hard to distinguish the two, and in most species - e.g. rats - there is only one structure called the striatum (what we call the caudate nucleus and putamen together)
3) Medially, there are two different segments - although called only one - which is called the globus pallidus.
The key features of the globus pallidus is that it is round and pale
There is an internal (medial) and external (lateral) segments
4) Underneath the thalamus, there is the subthalamic nucleus
5) Finally, more underneath and further back in the brain, is a structure called the substantial nigra (black substance)
Describe how the nerves enter the basal ganglia
Fibers from the planning part of the cortex send their connections down into the basal ganglia - specifically the striatum - and use glutamate as their major NT (the no. 1 excitatory NT in the brain - the cortex often uses it to communicate to other regions of the cortex or other subcortical regions)
The glutamate activity can be placed on three different types of neurons in the striatum that are remarkably similar but go to different regions
Where do the three neurons in the striatum lead to and what do they use?
One will go to the external segment of the globus pallidus
One will got to the internal segment of the globus pallidus
The final one will got down into the substantia nigra
All three of these neurons use Gamma Amino Butyric Acid (GABA) - the no. 1 most common inhibitory NT
(when you undergo a generous anesthetic, most what the anesthetic does is it increases the activity of the GABA receptors such that we essentially enter a subconscious mode)
What is in the substancia nigra
There is also another group of neurons that goes from the substancia nigra (pars compacta) that hold dopamine
What the substantia nigra does - through dopamine - is it sends the dopamine up to the the three inhibitory neurons within the striatum such that they are primed absolutely ready to fire (only require a tiny bit of NT to come in from somewhere to activate the inhibitory neurons and activate the rest of the basal ganglia circulatory)
Describe dopamine
Dopamine is an interesting NT in that it doesn’t have a particular positive or negative in and of itself, it acts on different types of dopamine receptors, and the protein structure of the receptor, determines whether you get a positive or negative response from the dopamine
Dopamine is also the NT that holds us level in our thinking:
- If you have too much dopamine, you will see things that aren’t there, you will engage in at risk activities, and generally act abnormally
- If you have too little dopamine, you will be stiff and rigid and be limited in thinking availability, and your executive function (e.g. ability to look at the alphabet and find letters across the page, and your ability to plan ahead etc.)
- Dopamine is also the NT that most psychoactive drugs work on, to some level
- 95% of Dopamine is made in the substantia nigra
Describe the function of the subthalamic nucleus
The subthalamic nucleus creates an alternative pattern of electrical/chemical flow through the basal ganglia - from the Globus pallidus exterior to the new neuron in the globus pallidus interior so that you have two circuits that compete with one another.
In this competition the best scenario wins, and ultimately the neuron body in the globus pallidus internal segment, is responsible for sending an inhibitory signal to the thalamus, and in the thalamus there is a final fibre (an excitatory fibre) that goes back up into the primary motor cortex
What is in the thalamus
Within the thalamus there is a final excitatory fibre that goes back up into the primary motor cortex to activate upper motor neurons
Describe Parkinson’s disease
One of the most common diseases (2nd) in the brain is Parkinson’s disease, which is where we end up with a loss in the amount of dopamine - the substantia nigra loses about 60-80% of the dopamine neurons before one gets the symptoms of the disease.
Due to this loss of dopamine production, the three neurons in the striatum are no longer primed
Although this means that more glutamate will be produced to accommodate and send the message, the problem is that glutamate is toxic if you don’t mop it up - done via astrocytes. Therefore, if there is minimum dopamine and more glutamate is being sent in, the neurons will get too much glutamate
What this means is that the neuron in the striatum cannot do what they need to do, which is inhibiting the next neurons, which means that the next neurons will be firing more and you inhibit the final thalamus neuron which activates the upper motor neuron.
Overall, this means that the amount of excitation in the primary motor cortex decreases - we have hypoexcitation (which results in hypoactivity of the muscle - stiffness, rigidity, difficulty in initiating movement)
- note that there is difficulty in initiating movement as this is something that the basal ganglia is important for
What are Parkinson’s symptoms
What you would expect to see with someone with Parkinson’s disease is a distinctive movement disorder - stiffness, rigidity, difficulty in initiating movement
e.g. you could call them in the waiting room, and they would shuffle to the edge of their seat, eventually get up, and look like they are about to fall over but end up walking normally after a while, there may be a gait problem, and often hunched with a pill rolling tremor, and usually expressionless as they don’t express mood through their movement due to the failure in the basal ganglia
Describe how movement is initiated vs cessated
mportantly, one of the things that the basal ganglion is good at is initiating movements, while the role of the cerebellum - which has neurons that input to the same neurons in the thalamus - is to cessate/stop movement.
Therefore you can tell if someone has a problem with their cerebellum if one isasked to touch their hand and touching their nose - as if they push their hand or overshoot the nose and touch their face, they may not be able to cesate movement at the right time
How are dopamine levels normally
Under normal circumstances you have a normal level of dopamine - which is essentially constant and sent out in microtires (just enough)
How can you increase dopamine levels
If you engage in something thrilling, or take an illicit substance you may increase dopamine
Describe levodopa
In 1961, someone came up with the idea of using levodopa - a precursor to dopamine - to give to people who got parkinson’s disease due to the 1918 flu pandemic.
It was identified that if they because deficient of dopamine due to the flu and took levodopa the remaining cells could turn the levodopa into dopamine and it was reasonably successful
However, when they took it their levels could shoot up such that they have psychosis or depression
This can be the reality of those with Parkinon’s 2-3 or up to 6-8 times a day over the course of a few years
What happens is the symptoms (at the top) sound more like schizophrenia, and one of the reasons why people who have schizophrenia don’t take their medication (almost all antiphychotics bring down the dopamine levels) is that it makes them stiff and rigid (causes the opposite problem - giving them some of the symptoms as Parkinson’s disease)
What are the alternatives for Parkinson’s (other than dopamine replacement drugs like levadopa)
Surgical lesions - pallidotomy and thalamotomy (treatments developed by accident by a neurosergeoun that had a paitent with such severe parkinsons that they thought to cut the parametal tract, and as he went in he found a spasming artery and aborted in case a stroke occurred, and afterwards the patient didn’t have parkisons disease, so the artery must have been important, and the artery was responsible for supplying the globus pallidus internal segment with blood, so he figured that if you lesion that region of the brain you can remove parkinsons as there are less active inhibitory neurons and the pathway to the motor cortex fires as normal/more, one of the quirks of the surgeryis that it works brilliantly on one side, but doesn’t work very well if you do it on both sides)
Deep brain stimulation (common for those who have sever movement disorders than cognitive side for parkinsons) - now in NZ we have 20people paid for byt the government to ge thetis, which is where they insert a very thing electrode into the brain to activate the cells that would usually be activate by the basal ganglion circulatory but with lower reliance of dopamine
When do Parkinson’s patients first get treated
It is important to note that all of this treatment occurs when 60-80% of these neurons are dead - so f we could treat it before the cells die, we could sotp people going to the doctor with a movement disorder and instead a smelling or bowel disorder (what happens before the movement disorder)
