Physiology of Neurodegenerative Disease

Question 1

Grey vs White Matter

Answer 1

The CNS has two kinds of tissue: grey matter and white matter
Grey matter, which has a pinkish-grey color in the living brain, contains the cell bodies, dendrites and axon terminals of neurons, so it is where all synapses are.
Darker: Contains cell bodies in larger densities

White matter is made of axons connecting different parts of grey matter to each other. Signal pathways

Question 2

Neurons

Answer 2

Function is determining factor in morphology

Question 3

Glial cells

Answer 3

Space-fillers
Not a critical role
10x more than neurons, indicating that they must be important for neuron function
Wrap around axons as Myelin

1. Maintain ionic balance (k+)
2. Modulate the rate of nerve signal propagation
3. Uptake of neurotransmitters (glutamate)
4. Regulate the recovery of neurons from injury
5. Form epithelium in ventricles and other functions

Question 4

Chemical Synapse

Answer 4

Info passes chemically, in the form of neurotransmitters (glutamate, GABA, ACh)
Takes longer than gap synapse; minutes to hours

1 and 2: Electrical signal is translated into chemical message (neurotransmitter) by presynaptic neuron at presynaptic terminal

3: Synaptic vesicle fuses with synaptic cleft and neurotransmitter “swims” across the synaptic cleft until it reaches the other neuron (passing through the postsynaptic neurotransmitter receptor on postsynaptic membrane)
4. Other neuron translates the chemical signal back into an electrical one
5. Chemical signal is degraded

Question 5

Electrical Synapse

Answer 5

Signal is sent through gap junction channels from the cytoplasm at the presynaptic membrane to the neighboring neuron

1. Direct passage of molecules/ions
2. Synaptic cleft is only 3.5nm vs 50 in neuromuscular
3. Conduction in both directions
4. Inactivated by H+ or Ca2+
5. Useful in reflex pathways and during development

Question 6

Neuromuscular Junction

Answer 6

Type of chemical synapse (using ACh)

1. Synaptic cleft is 50 nm
2. Conduction in one direction
3. Synaptic delay is 1 ms

Question 7

Excitatory Postsynaptic Potential (EPSP)

Answer 7

Depolarization of the membrane due to transient increase in Na+ or Ca2+ conductance

Question 8

Inhibitory Postsynaptic Potential (IPSP)

Answer 8

Hyperpolarization of the membrane due to transient increase in K+ or Cl- conductance

Question 9

Axon hillock

Answer 9

Initial segment, action potential originates here

Question 10

Spatial summation

Answer 10

Spatial summation occurs when excitatory potentials from many different pre-synaptic neurons cause the post-synaptic neuron to reach its threshold and fire.

Using many shovels to fill up a hole at once

Question 11

Temporal summation

Answer 11

Temporal summation occurs when a single pre-synaptic neuron fires many times in succession, causing the post-synaptic neuron to reach its threshold and fire.

Using one shovel to fill up a hole over time

Question 12

Gap junction channels

Answer 12

The pores connecting cytoplasm of two neurons in electrical synapses

Each contains 6 connexin subunits

Question 13

Association Cortex

Answer 13

~75% of cortical area
Functions to:
1. Integrate (associate) info from various brain regions
2. Influence (modulate) a broad range of behaviors/functions

Responsible for cognitive ability

Question 14

Primary Sensory and Motor Areas

Answer 14

~25%; Grey

Question 15

Classifications of Human Memory

Answer 15

1. Nature of what is being remembered (declarative or procedural)
2. Time over which it is effective

Question 16

Declarative Memory

Answer 16

Available to consciousness

Daily episodes, words and their meaning, history

Question 17

Procedural Memory

Answer 17

Not available to consciousness, cannot be described in words

Motor skills, associations, priming cues, puzzle solving skills

Question 18

Time Memory

Answer 18

Immediate memory or sense of the present >
Short term memory (7 random digits) >
Intermediate term memory >
Long term memory>

All can lead to forgetting

Question 19

Acquisition and storage of declarative information

Answer 19

Short term memory storage: hippocampus
Long-term memory storage: variety of cortical sites
(Wernicke’s for meaning of words)
(Temporal cortex for memories of objects & faces)

Question 20

Acquisition and storage of procedural information

Answer 20

Short term memory storage: sites unknown but presumably spread
Long-term storage: Cerebellum, basal ganglia, premotor cortex, other sites related to motor behavior)

Question 21

Amnesia

Answer 21

Pathological forgetting
Mental ability is normal
No difficulty in perception
Abstract thinking is normal
Declarative long-term memory is normal
Procedural ST and LT memories are normal

Anterograde: inability to form new memories (hippocampus is damaged)
Retrograde: inability to retrieve old memories (occurs following damage to some cortical areas)

Question 22

Korsakoff Syndrome

Answer 22

Amnesia (anterograde > retrograde)
Caused by vitamin B1 deficiency and associated destruction of mammillary bodies
Seen in alcoholics as a late neuropsychiatric manifestation of Wernicke encephalopathy
Confabulations (fabricated memories)

Question 23

Causes of Amnesia

Answer 23

Vascular occlusion of both posterior cerebral arteries (bilateral medial temporal lobe, hippocampus)

Midline tumors (medial thalamus, bilaterally)

Trauma or surgery or infections (bilateral medial temporal lobe)

Vitamin B1 deficiency (medial thalamus and mammillary bodies

ECT for depression

Question 24

Brain size

Answer 24

Peaks at about 15-20 years of age
Decrease is due to loss of some neuronal circuitry (synapses and neurons), resulting in decreased memory functions

Neurodegeneration and memory loss can occur during some diseases

Question 25

Pathology of AD

Answer 25

Loss of neurons and synaptic connections in hippocampus, entorhinal cortex, and amygdala, leading to dissociation of hippocampus and cortex

Loss of neurons in basal forebrain nuclei (ACh, 75% loss), locus coeruleus (norepinephrine, NE), and raphe nuclei (serotonin; 5-HT)

Question 26

Pathology of AD

Answer 26

Loss of neurons and synaptic connections in hippocampus, entorhinal cortex, and amygdala, leading to dissociation of hippocampus and cortex

Loss of neurons in basal forebrain nuclei (ACh, 75% loss), locus coeruleus (norepinephrine, NE), and raphe nuclei (serotonin; 5-HT)

Glutamate-mediated excitotoxicity

Question 27

Type of glial cells

Answer 27

Astrocyte (CNS)
Satellite cell (PNS)
Oligodendrocyte (CNS)
Schwann cell (PNS)
Microglial (phagocyte)
Ependymal cell

Question 28

What is the main function of the neuron?

Answer 28

To generate action potentials

Question 29

Neuronal action potential

Answer 29

Resting: negatively charged

Occurs when membrane potential of a neuron rapidly rises and then falls

Generated by voltage-gated ion channels embedded in cell’s plasma membrane

Voltage gated Na+ channels: responsible for raising phase of action potential

Question 30

Gap junction -permeable “death signals” and pharma agents

Answer 30

From dying (injured) neurons to healthy neurons

One of the mechanisms that determines the amount of neuronal death during acute brain injuries (stroke) and chronic neurodegenerative diseases (AD)

Development of pharma agents that block neuronal gap junctions may provide neuroprotection in brain diseases