Physiology of Neurodegenerative Disease Flashcards
Grey vs White Matter
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
Neurons
Function is determining factor in morphology
Glial cells
Space-fillers
Not a critical role
10x more than neurons, indicating that they must be important for neuron function
Wrap around axons as Myelin
- Maintain ionic balance (k+)
- Modulate the rate of nerve signal propagation
- Uptake of neurotransmitters (glutamate)
- Regulate the recovery of neurons from injury
- Form epithelium in ventricles and other functions
Chemical Synapse
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
Electrical Synapse
Signal is sent through gap junction channels from the cytoplasm at the presynaptic membrane to the neighboring neuron
- Direct passage of molecules/ions
- Synaptic cleft is only 3.5nm vs 50 in neuromuscular
- Conduction in both directions
- Inactivated by H+ or Ca2+
- Useful in reflex pathways and during development
Neuromuscular Junction
Type of chemical synapse (using ACh)
- Synaptic cleft is 50 nm
- Conduction in one direction
- Synaptic delay is 1 ms
Excitatory Postsynaptic Potential (EPSP)
Depolarization of the membrane due to transient increase in Na+ or Ca2+ conductance
Inhibitory Postsynaptic Potential (IPSP)
Hyperpolarization of the membrane due to transient increase in K+ or Cl- conductance
Axon hillock
Initial segment, action potential originates here
Spatial summation
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
Temporal summation
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
Gap junction channels
The pores connecting cytoplasm of two neurons in electrical synapses
Each contains 6 connexin subunits
Association Cortex
~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
Primary Sensory and Motor Areas
~25%; Grey
Classifications of Human Memory
- Nature of what is being remembered (declarative or procedural)
- Time over which it is effective
Declarative Memory
Available to consciousness
Daily episodes, words and their meaning, history
Procedural Memory
Not available to consciousness, cannot be described in words
Motor skills, associations, priming cues, puzzle solving skills
Time Memory
Immediate memory or sense of the present >
Short term memory (7 random digits) >
Intermediate term memory >
Long term memory>
All can lead to forgetting
Acquisition and storage of declarative information
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)
Acquisition and storage of procedural information
Short term memory storage: sites unknown but presumably spread
Long-term storage: Cerebellum, basal ganglia, premotor cortex, other sites related to motor behavior)
Amnesia
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)
Korsakoff Syndrome
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)
Causes of Amnesia
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
Brain size
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
Pathology of AD
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)
Pathology of AD
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
Type of glial cells
Astrocyte (CNS) Satellite cell (PNS) Oligodendrocyte (CNS) Schwann cell (PNS) Microglial (phagocyte) Ependymal cell
What is the main function of the neuron?
To generate action potentials
Neuronal action potential
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
Gap junction -permeable “death signals” and pharma agents
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
