Final Exam
What are the primary motor cortex and somatosensory cortex involved in?
Simple Finger Flexion
What is the supplementary motor area involved in?
Mental rehearsal
What areas are involved in sequential finger movements?
Supplementary motor cortex, primary motor cortex, and somatosensory motor cortex
What area is involved in mental rehersal of finger movements?
Supplementary motor cortex
What is the dorsal pre motor cortex involved in?
Motor planning
What is the ventral premotor cortex involved in?
Grasp function. Only fire when people are moving--doesn't fire when pliers pick something up
Explain the Lateral Corticospinal Tract (Pyramidal Tract) and draw it.
Carries movement for arms and legs
Starts at an upper motor neuron in the primary motor cortex, travels down the spinal cord and decussates at the medulla (bottom of brain stem), then travels to the anterior horn of the spinal cord where it will transmit the information via lower motor neurons
What are Betz cells? Where are they found?
Largest cell in the cortex, they control how we move. They are found in layer 5 of the primary motor cortex/corticospinal tract.
Explain the Dorsal Column- Medial Lemniscal Pathway and draw it.
This pathway is for proprioception of the contralateral side and light touch
Starts at finger nerves which carry information to the spinal cord (dorsal root ganglia/first order neurons) then travels to the dorsal column, comes to cunate nucleus and crosses over through medial lemniscus (second order neurons), synapses in the thamalus, then goes to the somatosensory cortex (third order neurons).
What is a muscle spindle?
A peripheral receptor, a stretch receptor that signals length and changes in length of muscles. It changes as the muscle is stretched
List some concerns individuals with a SCI have after their injury.
Mainly automonic troubles (sexual dysfunction, bladder/bowel dysfunction)
Severe swings of blood pressure which can lead to:
-increased risk of stroke (3-4x)
-increased cardiovascular risk (2-3x)
-Dizziness, light-headedness, confusion
Explain/draw the sympathetic and parasympathetic neurotransmitters and receptors.
Sympathetic:
Preganglionic neuron travels from it's origin to a ganglion and releases acetylcholine and are excitatory.
Postganglionic neuron travels from the ganglion to the smooth muscle or gland being innervated and releases norepinephrine. They can be excitatory or inhibitory on the end organ.
Parasympathetic:
Preganglionic neuron travels from it's origin to the ganglion and releases acetlycholine. Post ganglionic neuron travels from the ganglion to the smooth mucle or gland being innervated and releases acetlycholine. It can be excitatory or inhibitory on the end organ.
Sympathetic system has a bigger neuronal divergence (1:17) than the parasympathetic system (1:2).
Name three things the baroreflex effects.
Heart rate, vascular tone, and kidneys/increases arterial pressure
What is more important for regulating blood pressure/during orthostasis? Heart rate or blood vessels. Why?
Blood vessels/vasculature are more important for regulating blood pressure. Pressure = blood flow/tube radius^4
Explain the natural baroreflex. What happens if someone has a spinal cord injury?
1. When you sit up your blood pressure will drop which is detected by carotid arteries and the aortic arch, specifically the baroreceptors (stretch mechanoreceptors).
2. The information gets sent to the brain stem, specifically the nucleus tractus solitarious (NTS)
3. NTS will tell the rostroventral lateral medulla (RVLM) to become more excited and produce more sympathetic outflow
4. Outflow is transmitted through descending sympatho-excitatoty neurons. Tyrosine hydroxylase (TH) is use to detect where sympathetic descending fibres are. These fibres travel down to the spinal cord
5. In the spinal cord the sympathetic preganglionic neurons will project to post ganglionic fibres that are touching blood vessels, causing them to constrict and raise blood pressure. Acetyle cholinesterase (ChAT) is used to indicate the sympathetic fibres in the spinal cord.
When you have a spinal cord injury the descending sympathetic outflow doesn't work. The afferent arm of the baroreflex is still intact (can still detect changes) but can't adjust to account for these changes.
What is transient blood pressure lability associated with?
Transient severe swings in blood pressure are one of the primary disorders after spinal cord injury. It leads to:
3-4x increase in risk of stroke
2-3x increase of cardiac events
Daily episodes of dizziness, light-headedness, confusion
___ ___ reduces autonomic dysregulation. Explain.
Excitatory inhibition reduces AD.
Reducing the number of excitatory synpases for VGlut onto preganglionic neurons at electrical stimulation point at T2 dynamic hotspot region
What information do A(alpha) primary afferent neurons carry? Are they heavily mylenated or not?
They carry proprioception and are the most mylenated and have the widest diameter of axon (carry information the fastest)
What information do A(beta) fibres carry? Describe their characteristics.
They carry mechanoreception. Their axons are the second largest in diameter (6-12um), mylenated, and second fastest transmission speed.
What information do A(delta) primary afferent neurons carry? Describe their characteristics.
They carry fast nociception and temperature. They have a small diameter of axon and lightly mylenated. Don't carry information too quickly. They are fast, sharp pain.
What information do C primary afferent neurons carry? Describe their characteristics.
They carry information about slow nociception, temperature and itch. They are very thin fibres and are not mylenated. They carry information slowly compared to the other neurons. They carry dull, slow pain you feel after the injury.
Explain common properties of somatosensory receptors.
Modality
Specific: most respond preferentially or exclusively to certain stimuli
Multimodal receptors: Possess low threshold for one stimulus and a higher threshold for another stimulus
Receptors are part of the peripheral nervous system
Ability to adapt
-some adapt quickly (mechanoreceptors) and some adapt slowly (pain receptors)
Tonic Receptors:
Slow acting/adapting OR no adaptation (continue to respond to impulses as long as they are there (proprioreceptors))
Provide information about a steady state stimulus
Phasic receptors:
Quick acting
Adapt: stops firing when stimulus is constant (smell)
Provides information about change in stimulus
Reacts strongly when stimulus is changing
Defined receptive field
An area of the body subserved by the receptor
Smaller RF = better ability to tell two points apart (greater acuity)
Compare Tonic vs Phasic receptors.
Tonic Receptors:
Slow acting/adapting OR no adaptation (continue to respond to impulses as long as they are there (proprioreceptors))
Provide information about a steady state stimulus
Phasic receptors:
Quick acting
Adapt: stops firing when stimulus is constant (smell)
Provides information about change in stimulus
Reacts strongly when stimulus is changing
Name and describe the four types of mechanoreceptors.
Mechanoreceptors are involved in all aspects of touch (pressure, vibration, movement) and are mostly carried by A(beta) fibres.
Merkel's Discs
Located in epidermis (superficially/close to surface-makes them more sensitive and easier to get to)
Respond to light touch and pressure/low Hz vibrations
Slowly adapting
Small receptive field
Sense steady state pressure and texture
Dense in finger tips, lips and genetalia
Critical for tactile acuity (can distinguish verticle from horizontal lines)
Meissner Corpuscle
In superficial layers of the skin (close to the surface)
Small receptive field
Responds to light touch and vibrations (<50Hz)
Fast adapting
Detects movement of textures across skin
Ruffini's Corpuscles
Lie parallel to skin (deeper in skin)
Large receptive field (less sensitive)
Senses stretch by digit or limb movements, skin tension, position and movement
Slow adapting
Pacinian Corpuscle
In subcutaneous tissue
Large receptive field
Responds to pressure (i.e., poke)/deep touch
Fast adapting (adpats faster then Meissner's and lower response threshold)
Discrimination of fine surface textures
Describe Merkel's Discs.
Merkel's Discs
Located in epidermis (superficially/close to surface-makes them more sensitive and easier to get to)
Respond to light touch and pressure/low Hz vibrations
Slowly adapting
Small receptive field
Sense steady state pressure and texture
Dense in finger tips, lips and genetalia
Critical for tactile acuity (can distinguish verticle from horizontal lines)
Describe Meissner Corpuscles.
In superficial layers of the skin (close to the surface)
Small receptive field
Responds to light touch and vibrations (<50Hz)
Fast adapting
Detects movement of textures across skin
Describe Ruffini's Corpuscles.
Lie parallel to skin (deeper in skin)
Large receptive field (less sensitive)
Senses stretch by digit or limb movements, skin tension, position and movement
Slow adapting
Describe Pacinian Corpuscle.
In subcutaneous tissue
Large receptive field
Responds to pressure (i.e., poke)/deep touch
Fast adapting (adpats faster then Meissner's and lower response threshold)
Discrimination of fine surface textures
True or false. Nociceptors are polymodal (can transfer multiple sensations)?
True. They can transfer mechanical pain, hot, cold, itch. They use A(delta) and C fibres to do so.
Explain the spinothalamic tract.
It is a type of pain pathway. Information is carried from the hand (first order neurons) to the spinal cord where it decussates (second order neurons), then to the thalamus and into the sensory cortex (third order neurons). It transferes pain, temperature, coarse touch, and intensity and location of pain.
What are the three key drivers of TBI pathology?
Bioenergetic dysfunction
Excitotoxicity
Neuroinflammation
Explain bioenergetic dysfunction.
When there is a TBI there is a reduction in cerebral blood flow (vasoconstriction) because of vasculature damage. Damage leads to neurotransmitters with vasoactive properties leaking out which can cause constriction which leads to hypoperfusion (less blood flowing to the brain in this area). This leads to less oxygen and glucose to that area.
Explain ionic dysregulation.
Happens after a TBI. Ca influx, K dysregulation which leads to neurotransmitter dysfunction in terms of release.
Can happen after mechanical injury.
Mechanoporation occurs through a mechanism when the phospholipids in the plasms membrane bilayer will rearrange and form pours in the cell membrane where we have unrestricted and unregulated inon influx across the electrochemical gradient leading to dysregulation of ions and charge separation.
Dysregulation of ion flow can lead to other pathological states. If there is high Ca in the cell this can leads to protease acivation which further chew up essential proteins across a number of signalling cascades which will disrupt healthy cell behaviour.
Explain mechnoporation and how to restore it.
Occurs through a mechanisms when the phospholipids in the plasma membrane bilayer will rearrange and form pours in the cell membrane where we have unrestricted and unregulated ion flux across the electrochemical gradient leading to dysregulation of ions and charge separation.
It causes dysregulated ion flux and depolarization. To restore this ATP-dependent ionic pumps shift into overdrive causing hyperglycolysis, depletion of energy stores and increased ADP.
Larger increases in Ca influx are combated by sequesteration into mitochondria but ultimatley leads to mitochondrial dysfunction and oxidative stress/imbalance.
What happens if production of ATP is disrupted?
Ionic imbalance. Disruption to our health. Neurons can't fire and communicate properly.
Summarize what happens after a TBI.
Less blood flow to the brain (less glucose and oxygen)
Mechanoporation -> phospholipid bilayer rearranged
Dysregulated ion flux
ATP in overdrive = why we get hyperglocolysis, energy stores depleted
Large increase in Ca -> mitochondrial dysfunction
Explain the role of astrocytes in excitotoxicity.
Normally astrocytes help buffer synaptic glutamate by taking it up into their cells (by EAAT or GLT1) where it can be metabolized and recycled. In TBI there is a significant reduction in GLT1 transporters so glutamate can't be taken up into the astrocyte anymore. This leads to glutamate excitotoxicity.
What is the normal/healthy role of tau?
Tau is a microtubule stabilizing protein. It binds to and stablizes microtubules involved in polymerization of cytoskeletal networks that are involved in normal and healthy function of a cell
What happens with tau after repeated injury?
Classes of kinases will hyper phosphorylate tau and then it can't bind to microtubules, which leads to microtubule depolymerization.
Taus then form oligomers and neurofibrilary tangles which float around in the cytosol and eventually lead to cell death. With too much acumulatopn the cells will burst and be released into the extracellular milieu in the brain paranchyma and continue to drive pathology. This activates microglia, as they detect them as bad and try to clear them. If the microglia get overwhelmed it will lead to chronic neuroinflammation.
Explain the role of TDP-43.
In a healthy brain TDP-43 keeps tau in check by binding to tau, causing its degradation.
TDP-43 is a transcriptional repressor that binds to UG(n) repeates in the 3'-UTR of tau mRNA causing its degradation.
What happens to TDP-43 in CTE?
TDP-43 loses it's nuclear localization signal (NLS) (due to upregulation of AMPARs) and gets cleaved and truncated and can't stay in the nucleus to bind tau mRNA and facilitate it's degradation. TDP-43 gets phosphorylated and ubiquitinated causing cytosolic aggregation.
Explain pattern separation. Where does it occur?
When memories/inputs are very similar the memories must be stored in ways that it mimizies their overlap so it can be efficiently retrieved. It is proposed to occur in the hippocampus at the level of the dentate gyrus.
Memories show some overlap when they are inputted, but as they go through the levels of the hippocampus and get outputted there are distinct patterms.
Increased or decreased neurogenesis impairs pattern separation? Explain evidence.
Decreased neurogenesis decreases pattern separation.
WT rats and rats with less neurogenesis were shown two triangles. When they were shown the same two triangles and a triangle and a square, the WT rats were more likely to activate the same population of CA3 neurons with the same figure compared to a similar one. The activation of the same population of CA3 neurons was equivalent in the rats that had less neurogenesis when they were shown the same and a similar figure.
Exposed animals to either two identical contexts,
When identical – lot of activation of the same neurons
When different, different neurons
When we knock out NG, the same neurons respond to both contexts, and we lose ability to discriminate between the two
Briefly explain what catFISH is.
You can use it to identify neuronal populations activated at two different times while doing behavioural experiments. This can be used to study the dynamic interactions of neurons associated with different behavioural stimuli.
Explain temporal encoding.
When two events are close together in time they are:
Encoded by different mature neurons because the activity of mature neurons is sparse.
They are encoded by the similar populations of immature neurons because the immature neurons are highly excitable.
When two events are far apart in time they are:
Encoded by different mature neurons because the activity of the mature neurons is sparse.
They are encoded by different populations of immature neurons because they are transiently highly excitable.
Explain what changes happen in CA1 with running.
Running (increasing neurogenesis) leads to forgetting, which leads to reduced activity in the CA1 region.
What is the role of perineuronal nets?
They are extracellular matrix components which typically surround parvalbumin inhibitory interneurons. They regulate the activity of interneurons and regional excitability and may have a role in stabilizing memories.
What happens to perineuronal nets with increased neurogenesis? Explain.
PNN expression is reduced in the CA1 with increased neurogenesis.
After running and mementine PNN expression was decreased in CA1 region. PNN expression is increased with increased age.
What happens if you use optogenetics to excite mature neurons in the CA1?
It will increase neurogenesis, leading to decreased freezing on memory task and decreased expression of PNNs. This may be modulated by the activity of immature neurons (because there are the same amount of immature neurons with and without increased NG?).
Explain the difference between mushroom and thin spines.
Mushroom spines have been potentiated. They have a higher expression of NMDA and AMPA receptors at the synpase.
Thin spines have the potential to potentiate.
What happens to thin spines with increased neurogenesis?
The number of thin spines increase with increased neurogenesis. This means they have the ability to learn new memories faster.
New neurons are more excitable than mature neurons. How do they not become too excitable? How do they not become less excitable?
GABA inputs develop on immature neurons before excitatory inputs which keeps them from being too excitable.
They aren't less excitable because in response to GABA, immature neurons have NKCC1 transporters which pump chloride into the cell, depolarizing it. KCC2 is on mature neurons which pumps chloride out, hyperpolarizing the cell.
What is the biggest non modifiable risk factor for AD?
Age
What is the biggest non-modifiable genetic risk factor for LOAD?
Having the APOE4 gene
Describe APOE2, APOE3, and APOE4
APOE2 is protective against AD
APOE3 is most common and there is no risk for AD
APOE4 carries the strongest genetic risk factor for LOAD
Define late onset vs early onset AD.
Late onset (sporadic), arrises after age 65, most common
Early (familial), arrises before 65, can be due to genetic or non-genetic factor
Both have the same pathology and similar levels of cognitive decline, but different causes.
Explain what happens to tau in AD.
Tau is a microtubule-associated protein normally located in the axon. In AD, tau is translocated to the somatodendritic compartment and undergoes hyperphosphorylation, misfolding, and aggregation, leading to neurofibrillary tangles.
Explain amyloid-beta in AD.
AB accumulates forming intermediate soluble oligomers that are synaptotoxic as well as insoluble B-sheet pleated amyloid fibrils that are the main component of dense core plaques.
What are amyloid beta plaques made up of?
They are made up of extracellular deposits of amyloid beta abundant in the cortex of AD patients. The plaques are classified into diffuse and dense-core
There's a reduction of which transporters in female 5XFAD mice? Explain the study.
There is a reduction of glutamate transporters in female 5XFAD mice. The study used markers of metabolism and found hypometabolism of RSC in female 5XFAD mice. Hypometabolism is linked to hyperactivity. Impairment changes here are seen early on.
Hyperactivity may mean there is decreased inhibition or increased excitability. This could mean an impairment in PV-interneurons, they have high energy demands and may be susceptible to regional metabolic impairments. This was found to be true in female 5XFAD mice, it's only the case later in time in male rats.
What breaks down PNNs?
ChABC
Animals injected with saline or AB, PV density doesn't change much (therefore AB doesn't cause PV interneurons to die).
If the PNN is broken down before administration of ChABC, then PV interneurons die following AB condition
What is the mechanism of cell death in PV interneurons?
Apoptosis inducing factor (AIF) is a mitochondrial protein that can induce caspase independent apoptosis.
AIF is regulated in a sex dependent manner (more AIF in female PV-INS). HSP70 is higher in males and is regulated by estradiol. Low estradiol = low HSP70 = greater AIF nuclear translocation. Females have greater AIF translocation, especially with age.