Neuroscience Week 1 - Cytology of Neurons

Rate of transport for: fast anterograde- slow axoplasmic- fast retrograde-

Rate of transport for: fast anterograde- 400-1000 mm/day slow axoplasmic- .2-3 mm/day fast retrograde- 250 to 400 mm/day

Explain what fast axonal transport is: -_____ transports vesicles from the cell body to the presynaptic sites -______ transports GF and degradative vesicles the opposite route -What is the Rate of transport for fast anterograde, slow axoplasmic, and fast retrograde transport?

-Fast axonal transport as an energy dependent process that involves microtubules (the highways that the materials move down on through the axon) and the microtubule based motor proteins (note: "energy dependent process" or "active process" means that these require oxygen in order to happen, so they would stop when we dont have oxygen — like in a stroke.. they require ATP ) -Vesicles formed in the cell body are actively transported (fast anterograde) by kinesin to presynaptic sites that can be located more than a meter away from the soma. -Growth factors and degradative vesicles caring aged organelles or aggregated proteins take the opposite route (fast retrograde) driven by dynein. Rate of transport for: fast anterograde- 400-1000 mm/day slow axoplasmic- .2-3 mm/day fast retrograde- 250 to 400 mm/day

-what are glial cells necessary for / how does that associate with neuronal diseases? -defects in astrocytes are associated with: -what happens in MS / what glial cell is involved?

-Glial cells are necessary for the development and maintenance of healthy neurons. Therefore, it is not unexpected that their dysfunction is associated with neuronal diseases. -Defects in astrocyte function are associated with several diseases including Amyotrophic Lateral Sclerosis (ALS), Parkinson's, and Huntington's disease -In multiple sclerosis (MS), the complex pathological process produces dysfunction and apoptosis of the oligodendrocytes leading to demyelination and neurodegeneration within the CNS

Fast Retrograde Transport: -What does this transport trace? -What kind of process is this? -What happens? -What is it driven by? -Why are GF's important? -What is the rate of fast retrograde transport per day?

Fast retro grade transport has been used to trace connections of neurons! Energy dependent process that involves microtubules and microtubule-based motor protein (dynein). Growth factors and degraded of vesicles carrying aged organelles or aggregated proteins are returned to the cell body for either repair or degradation, driven by dynein. Growth factors are important because they tell the cell what is needed at the periphery / inform the cell of what's happening in the periphery. Info is shuttled back to the cell body** Rapid transport also occurs in the retrograde direction from nerve endings toward the cell body, returning materials from terminals to the cell body either for degradation or for restoration and reuse. These materials are packaged in large membrane bound organelles. The rate of fast retrograde transport is about 250 to 400 mm/day*.. so it's slower than that of fast anterograde transport. As in fast anterograde transport, particles move along microtubules.

What was Ramon y Cajal, (Read P 27) a neurobiologist responsible for ?:

3 Doctrines: i) Neuron Doctrine: Neurons are the basic signaling units of the nervous system. Each neuron is a discreetly bound cell whose several processes arise from its cell body and there is no cellular continuity (there is always a gap or synapse between the cells). -Some believed the body was made u of individual cells and others thought it was one big continuous system. It was one of the last systems to establish the cellular component, it was hard to distinguish because the cell body only makes up about 10% of it, but eventually the neural doctrine was accepted. ii) Principle of dynamic polarization: Information flows in a precise and consistent direction within nerve cell. Information flows from the cell body to the terminal site of the nerve down the axon. iii) Principle of connection specificity - entails three important considerations: a) No cytoplasmic continuity between nerve cells. Each nerve cell is a discreetly bound cell, even at synapses there is a synaptic cleft separating the pre and post synaptic space. b) Nerve cells do not connect indiscriminately (randomly) to one another. We aren't born with 100 billion neurons and over 6-8 months we figure out what connects with what. c) Rather, each nerve makes specific connections at precise and specialized points of synaptic contact. They make contact with some postsynaptic elements but not others. Each nerve make specific connections are precise and specialized points of synaptic contact. This is seen especially in spinal cord issues where damage will lead to very consistent clinical deficits**

endocytosis

A process in which a cell engulfs extracellular material through an inward folding of its plasma membrane.

Reflex- -what is it -how is it made possible? -what do they not depend on? -list a few common examples

A simple, involuntary, and nearly instantaneous motor response to a given stimulus. It is made possible by local neural circuits (neurons/nerve cells) called reflex arcs. These do not depend on conscious thought or processing by the brain, and provides a simple understanding of how neurons function and communicate. Common Reflexes- Babinski, Patellar Tap, Pupillary Light Reflex

(hyporeflexia) is associated with: (hyperreflixa) is associated with:

As a general rule: 1.Decreases in reflexes (hyporeflexia) is associated with dysfunction in the peripheral nervous system 2.Increases in reflexes (hyperreflexia) is associated with dysfunction in the central nervous system.

How do glial cells play a role in brain cancer?

As we have seen, mature neurons have withdrawn from the cell cycle process and thus cannot replicate. Neuronal loss from disease or injury is this permanent. -Glial cells however retain the ability in adults to replicate. About half of all primary brain cancers are associated with glial cell (astrocyte) proliferation. Gliomas (cancers from glial cells) occur more often in men than women.

AXOPLASMIC (AXONAL) TRANSPORT -what is it? -how long can it reach? -what are the three ways constituations move within the axon?

Axonal transport is a highly sophisticated mechanism required to maintain neuronal health and function through a lifespan that may reach 70-100 years The separation between cell body (metabolic center) and nerve terminals (transmitting element) calls for the existence of a special transport system to bring newly formed membrane and secretory products from the Golgi apparatus to the end of the axon. It may reach as long as 1 meter in length. There are three ways by which constituents move within the axon: a) by Fast Anterograde Transport (forward moving)- cell body to axon terminal b) by Slow Anterograde Transport (forward moving)- cell body to axon terminal c) by Fast Retrograde Transport- axoplasmic transport.- axon terminal to cell body

What is proliferation and what does that mean for a neuron??

Mature neurons do not undergo proliferation (reproduction). Therefore, most disease processes that affect neurons are associated with neuronal degradation and loss.

Nerve cell bodies and axons are surrounded by _______ cells, which means: ______ How many more of these cells are in the CNS of vertebrates compared to neurons? What are they? What do they do?

Nerve cell bodies and axons are surrounded by glial cells (Greek glia = "glue"). There are between 10 and 50 times more glial cells than neurons in the CNS of vertebrates. Glial cells are support cells that help the neurons function more effectively. They are NON EXCITATORY!!!!

What are the three large groups neurons are divided into and what are they based on? -what kind of nerves are for sensory cells?

Neurons are classified into three large groups based on the number of neurites a) Unipolar cells: One neurite from the cell body -uncommon in mammals, often found in invertebrates b) Bipolar Neurons: Two neurites from the cell body -tend to be sensory and function, often seen in the eyes (vision and auditory system) c) Multipolar Neurons: Multiple neurites from the cell body -tend to be motor -Pseudo-unipolar sensory cell is mainly for spinal patellar tap reflex and found in the dorsal root ganglia When pseudo-unipolar cells start off, they are actually bipolar cells. But with maturation, the cell bodies retract into the dorsal root ganglia and they become pseudo unipolar.

NEURONS. -what are they and what makes them different?

Neurons are the functional units of the nervous system and differ from most other cells in the body in being EXCITABLE

1. There is strong evidence from developmental neurobiology, that retrograde transport has a role in informing the cell body (the side of macromolecular synthesis) about events that occur at the distant ends of axonal processes. Not everything transported in the axon benefits the cell. List 4 example neurotropic viruses and toxins How do these reach the CNS ? 2. In addition to someone of these neurotoxins, disruptions can occur at the transport mechanisms. Disruptions of axonal transport have been linked to Neurodevelopmental and Neurodegenerative diseases. Therapies and pharmacological interventions aimed at restoring the rates of axonal transport are considered a promising therapeutic strategy to slow the progression of Neurodegenerative diseases Disruptions of axonal transport have spin linked to Neurodevelopmental and Neurodegenerative diseases, that include:

Some neurotropic viruses and toxins (for example: herpes simplex polio Rabies Tetanus toxin These reach the CNS by ascending from peripheral nerve terminals to cell bodies by fast retrograde transport. _______________ Alzheimer's disease Amyotrophic lateral sclerosis (Lou Gehrig's disease) Huntington's disease Multiple sclerosis

-what is the estimated number of neurons in the brain? -how many different types of neurons are there? do they have common features? -how can nerve cells with similar properties produce different actions?

The best estimate is that the human brain contains about 100 BILLION neurons. Although nerve cells can be classified into perhaps as many as 10,000 different types, they nevertheless share many common features. An important point is that nerve cells with basically similar properties are able to produce very different actions because of specific connections with each other and with sensory receptors and muscle.

Slow Axoplasmic (axonal) Transport: -what happens here? -what is the rate of travel mm/day* -what does it carry?

The cytosol (cytoskeletal elements and soluble proteins) is transported down the axon by slow axonal transport. The slower component travels at a rate of 0.2- 3 mm/day* and carries the proteins used to make up the fibrillar elements of the cytoskeleton (neurofilaments and micro-tubules). These fibrous proteins constitute about 75% of the total protein moved by the slower component.

What is neuronal differentiation and the most dramatic distinction?

The feature that most dramatically distinguishes one neuron from another is shape, specifically the number and form of a neurons processes. More specifically, the number of neurites coming off the singular cell body.

What are the three FUNCTIONAL classifications of neurons?

a) Afferent: Neurons that carry information into/towards the nervous system.. -aka sensory neurons b) Efferent: Neurons that carry information out of/away from the nervous system.. -aka motor neurons c) Interneurons: Neurons that function between the affarent and efferent. They are the most numerous type of neurons in our nervous system

In most neurons, the cell body represents what percent of the cell's total volume? a. 10% b. 30% c. 50% e. 70%

a. 10%

What functional type of neuron is most prevalent in the vertebrate nervous system? a. afferent and efferent neurons b. interneurons c. glial cells d. Renshaw cells

b. interneurons

The motor molecule responsible for fast anterograde axonal transport is: a. myosin b. actin c. kinesin d. tropomyosin e. dynein

c. kinesin

Somatic efferent (motor neurons) fibers are classified as: a. unipolar cells b. bipolar cells c. pseudo-unipolar cells d. multipolar cells

d. multipolar cells

Microtubules are the essential stationary tract used for what type of axonal transport? a. fast anterograde axonal transport b. slow axonal transport c. fast retrograde transport d. all of the above e. a and c

e. a and c

Astrocytes serve the following functions with the exception of: a. buffering function by taking up certain neurotransmitters from the synaptic area b. nutritive function c. buffering function by taking up excess potassium released during high activity d. act as scavengers and remove neuronal debris e. none of the above since all are functions of astrocyte

e. none of the above since all are functions of astrocyte

What are the four morphologically defined regions of the neuron?

i) Dendrites- receptive portion of the nerve where incoming neurons will make contact and synapse to send the message to the next nerve. They can have as many as 10,000 different inputs coming onto the dendrites ii) Soma- cell body that represents the metabolic center of the nerve (keeps the rest of the body alive and houses many of the critical structures.. contains nucleus, Golgi apparatus, rough endoplasmic reticulum, smooth endoplasmic reticulum) only represents about 10% of volume of a typical neuron iii) Axon- Conducting element of the nerve where the action potential is propagated from one area of the nervous system to another area of the nervous system. Diameters affect the velocity and these can very from .2-20 microns in size, the large the diameter the faster the conduction. Can be covered with the glial cell called myelin which also increases velocity of the action potential up to 120 meters per second. iv) Terminal Zone- Transmitting element where we communicate with other nerves. Neurotransmitters are released to activate or inhibit other nerves

What are the two distinct classes of cells in the nervous system?

i) Neurons- excitable cells of the nervous system that provide communication. They are EXCITABLE, meaning they can generate an action potential ii) Glial cells- Support cells. NON-EXCITABLE, have a resting membrane potential but it can't be reversed.

Glial cells are probably not essential for processing information, but they are though to have several other roles, what are they? (7) :

i) Supporting element- provide firmness to the brain ii) Form Myelin- formed by the Schwann cells in the PNS and Oligodendrocytes in the CNS iii) Scavengers in the CNS- Glial cells will remove debris after injury or neuronal death iv) Buffer ions and neurotransmitters- The concentration of different ions or neurotransmitters is critical for normal functions. High areas of neuronal activity can lead to a buildup of ions or neurotransmitters that can lead to dysfunction. These need to remain constant and at a normal level which is accomplished by the buffering of glial cells. v) Guide neurons during development- During development, as we think about our spinal motor neuron in the ventral horn and the axon extending out to a peripheral muscle, in development the glial cells guide the neurons to their overall terminal site / destination. vi) Form the Blood Brain Barrier / CSF- formed by ependymal cells to make sure that certain things don't get into the brain vii) Nutritive function- Astrocytes attach to neurons and blood vessels which serve some sort of nutritive function shuttling some particles from the blood stream to our nerves

-What kind of reflexes do newborn infants exhibit? -Retained primitive reflexes can lead to / indicate what?

newborn infants exhibit several primitive / neonatal reflexes that are eventually suppressed with normal development of frontal lobes. Retained primitive reflexes can lead to developmental delays and related to disorders like ADHD, sensory processing disorder, autism, and learning disabilities

Glial cells in the vertebrate nervous system are divided in two major classes based on their _____: -What are the 2 major classes? give details about each:

size i) Microglia: very small. Act as the immune system to the CNS. Mobilized, increase in number after injury, infection and disease. Phagocytes from the peripheral nervous system are too large to cross the blood brain barrier, therefor the immune system relies on these microglia. ii) Macroglia: larger glial cells- 3 classes:. a) Oligodendrocytes: glial cells that provide myelin in the CNS -out of the list of 7, this one creates myelin b) Schwann cells: glial cells that provide myelin in the PNS -out of the list of 7, this one creates myelin c) Astrocytes: Most abundant class, star shaped glial cells -out of the list of 7, this one does everything but create myelin. Provides nutrition, forms the BBB, buffers, scavenges and supports