Neurons and Glia, Synaptic Transmission, and CNS Pathways Flashcards

1
Q

How many neuronal cells are in the brain? which has more cells, Gray or white matter? Which makes up the bulk (volume) of brain?

A

There are over 80 billion neuronal cells in the brain
GRAY matter has more neuronal cells in brain
Gray matter- 86 billion cells
White matter: 84 billion
white matter has Greater volume and makes up bulk, LARGER portion of brain

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2
Q

which kind of glial cells take up almost half of our brain’s total volume?

A

ASTROCYTES (bigger than neurons)

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3
Q

what are the types of Glial cells in the central nervous system?

A

Types of Glial cells in the CNS:
1. Astroglia
2. Oligodendroglia
3. Microglia
4. Ependymal cells

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4
Q

Which of the glial cells are the most numerous?

A

ASTROCYTES

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5
Q

Describe the characteristics for astrocytes, Oligodendocytes, Ependymal cells and Microglia

A

-Astrocytes: (projections to neurons/vasculature of brain)
1. Most NUMEROUS
2. regulate chemical environment of extracellular space (space between glial cells and neuron )
-a. potassium and other ions
b. neurotransmitter uptake and metabolism
3. have neurotransmitter receptors (react to release of neurotransmitters)
4. Part of Blood/brain barrier (allows for some things to get out of blood vessel and into nervous system; vice versa)

-Oligodendrocytes-
1. create Layers of membrane (myelin) that insulate axons
a. Node of Ranvier- (break in myelin sheath; uninsulated portion)
insulation of axon facilitates electrical Impulse along axon. (myelin sheath facilitates speed of transmission of axon and signal jump from node to ranvier)
-Ependymal Cells:
1. Line fluid cavities of the brain- Ciliated
-(help move fluid along space)
-Microglia
1. Phagocytic cells to gobble up debris-dying neurons, etc
(keep brain free of debris)

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6
Q

How much of brain do glial cells make up?

A

glial Cells make up 1/2 of brain (glial largest portion of brain; volume)

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7
Q

What does a typical neuron consist of?

A

Typical neuron consist of Cell body, dendrites, Axon and Terminal Bulb,

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8
Q

What are the roles of cell body, axon, dendrites and terminal bulb?

A

Cell body- central part of neuron that contains nucleus and process information from dendrites
Axons- long nerve fiber that transmits electrical impulses away from cell body (neuron) and towards another neuron
Dendrites- branches on neuron that accepts information from other neurons and transfers it along axon (bring info to the cell body)
terminal bulb- endpoints or knobs at end oi neuron that release neurotransmitters

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9
Q

What is a synapse?

A

Synapse- gap between 2 neurons

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10
Q

What are the basic types of Neurons?

A

Basic Neuron Types
1. Bipolar (interneuron)- one dendrite and one axon (at opposite poles)
2. Unipolar (sensory Neuron)-ONE axon that extends into its dendrites (seen in sensory neuron, spinal cord)
3. Multipolar (Motor Neuron)- one axon, multiple dendrites (collect info from different dendritic inputs)
4. Pyramidal cell- pyramid shape that have two distinct trees and apical dendrites and basilar dendrites (a form of multipolar neurons)

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11
Q

Describe the main components of a cell and their roles. Which parts of the cell or neuron needs a lot of energy?

A

Main components of a cell:
-Nucleus- transcription (DNA)
-Rough ER (endoplasmic reticulum) - Abundant; site of protein synthesis - outer membranes
-Free ribosomes- (polyribosomes)
-site of protein synthesis- cytosol

-Smooth Endoplasmic reticulum
-protein folding
-calcium balance, storage and release
Golgi apparatus-
-posttranslational processing of proteins
-sorting and distributing of proteins to different locations- soma, axon, synapse
Mitochondria- (energy supply)
-Large number in soma
-large number in synapse
neurons need a lot of energy in nucleus for protein production
need a lot of energy at synaptic end of neuron for release and reuptake of neurotransmitters

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12
Q

Describe the unique structures in a neuron and their roles

A

Unique structures of a neuron:
1.Soma- centralized portion (gives rise to dendrites)
2. Cytoskeleton- gives shape to neuron (maintain structure of axons and dendrites)
3. Axon- unique to neurons (mm to one meter long
-transmit electrical signals from soma to synapse over short or long distances
-protein composition of axons is different than Soma membrane
4. Dendrites- have polyribosomes- local protein synthesis occurs
-dendritic spines- (protrusions, )serve as site of information transfer (from one neuron to another)
Synapse- Site of electrical or chemical transmission

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13
Q

what are the specialized design features for neurons?

A

Specialized design features: Neurons
Unique gene products ; they produce proteins for neurotransmitter synthesis and packaging of neurotransmitter and receptor sub-units: give rise to cytoskeleton (maintains shape and structure of neuron)
-location of mitochondria (energy for soma, synapse) (distribution of mitochondria according to location)
-microtubules for structural support and axonal transport
-protein composition of membrane varies according to cell location:
free ribosomes- cytosolic proteins
Rough ER- membrane proteins
-cells have Heterogenous shapes and sizes
-Neurons are defined by their transmitters: acetylcholine- motor neurons

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14
Q

How are neurons defined?

A

Neurons are defined by their TRANSMITTERS

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15
Q

Describe the different features and components of an axon. What makes an Axon unique?

A

Axon contains:
1.Axon Hillock- where action potential is generated along axon to synaptic terminal
2. Nodes of Ranvier- sites of discontinuous myelin sheath from Oligodendrocytes
(sites where electrical signal jump from one end to another)
3. Axon terminal (bouton)- one of synaptic end that allows reuptake of neurotransmitter
4. Axon varicosities- enlargements along axon where neurotransmitters are synthesized, released and packaged
5. Axon collaterals and recurrent collaterals-
axon collaterals- branch of axon
recurrent collaterals- where axon branches and reinervates same cell or adjacent cell (modulate cell firing pattern)
Unique features for Axon - NO protein synthesis
-NO rough ER
NO free ribosomes

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16
Q

What are the components of cytoskeleton? what is the axon skeleton composed of ? What is Axon railway system ?

A

Cytoskeleton (elements that keep the shape of axons and dendrites ) composed of :
-Microtubules, neurofilaments and microfilaments
-Axon skeleton (structure) - microtubules (24 nm, tubule), neurofilaments (10 nm), and MICROFILAMENTS - that give neuron its SHAPE (5-7 nm; actin)
-Axon railway system- (Microtubules) transport materials along axon between soma and synapse

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17
Q

What are the two main types of axonal transport ?

A

Types of Axonal Transport:
- Fast axonal transport- occurs at a rate of 20-40 mm/day (RAPID, ACTIVE process)
-Fast Anterograde transport- (up top 400 mm/day; from soma to synapse)
- carries organelles, enzymes, synaptic vesicles and small molecules
-fast Retrograde transport (from synapse back to soma)
-for recycled materials and pathogens; rabies, herpes simplex, tetanus, polio viruses (from synapse back to soma)
-delay between infection and symptoms is time needed for transport up the axon
Slow axonal transport or AXOPLASMIC FLOW- 0.5 to 10 mm/day
-always ANTEROGRADE (soma to synapse)
-slower process
-moves enzymes, cytoskeletal components, and new axoplasm down the axon during Repair and Regeneration of damaged axons
-Damaged nerve fiber regenerate at a speed governed by slow axonal transport

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18
Q

what are the two types of proteins seen during axonal transport? are they part of retrograde or anterograde transport?

A

proteins: Kinesin and dynen
1. Kinesin- has synaptic components, cytoskeletal structures and ion channels
-have carrier system that uses ATP to walk cargo from soma to synapse
-ANTEROGRADE Transport
2. Dynein- has cargo for degradation, and neurotrophic signals
-moves from synapse back to soma
-RETROGRADE Transport
these transport proteins need ATP to carry cargo.

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19
Q

Describe the process of synaptic transmission

A

synaptic transmission process:
-store neurotransmitter in neuron
-release it from the nucleus
-this impulse will travel down the axon
-this prompts synaptic vesicles (contain transmitters) to migrate to pre-synaptic membrane
-fusion with membrane and dumping of transmitters located vesicles into synaptic cleft
transmitter migrate across synaptic cleft and activates dendrites of post-synaptic membrane.

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20
Q

describe the cell morphology seen with purkinje cell, pyramidal cell, and motor neuron of spinal cord

A

Purkinje cell- (seen in cerebellum); dendritic tree where cell can integrate information from many different channels
Pyramidal cell- apical dendritic tree, basilar set of dendrites, single axon
motor neuron of spinal cord- cell body, dendrites, single axon that travel Long distances to muscles (to activate muscles to carry out motor functions

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21
Q

How can information be processed when viewing cross-section of spinal cord? What is important for processing information in spinal cord ?

A

information enters to dorsal portion of spinal cord and ascends to higher level;
info travels down Spinal cord to ventral portion that innervates motor neuron (sends axon to muscle)
-*even at level of spinal cord there is CIRCUITRY involved in processing information in ascending and descending portions of spinal cord (using inhibitory (interneuron) and excitatory neurons activate circuit

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22
Q

Describe the different channels that are on Neuronal membranes

A

Neuronal membrane:
1. Na+ K+ ATPase (pump): maintains the balance between sodium and potassium outside and inside cell(has enzyme that maintains [ } gradient)
2. Receptors - are the target of different kinds of neurotransmitter molecules (like peptides, Amino acids, catecholamines.
-catecholamines- activate receptor and cause inhibition/activation of the cell.
3. Na+ channel: pore In the membrane: when channel is open, allows flux of Na+ ions to go from out of cell to inside cell, creating voltage change (basis for activating psot-synaptic neuron)
4. K+ Channel- which when open, allows for efflux of K+ ions( to go from inside to outside cell) leafing to voltage change
5. Cl- Channel- that changes voltage of membrane (with efflux of Cl- ions) and gives rise to activation of electrical synaptic cell
There are also Transmitter receptors, transmitter reuptake pumps, ligand gated or voltage gated ion channels.

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23
Q

Which two categories do transmitter receptors fall into? How do they work
what is role of transmitter reuptake pumps?

A

Transmitter receptors:
1. G protein Coupled receptor-
INDIRECT ACTION - to change excitability series of steps, use secondary messengers.
ligand binds to channel, which activates or inhibits adenylate cyclase (convert ATP to cyclic AMP) Cyclic AMP is used as a second messenger inside cytosol. cAMP can do different things
-ligand binds to receptor, which triggers sequence of events that shuts down or stimulates the production of Cyclic AMP, which then acts as second messenger, causing an action in cytosol and affects excitability of neuron

  1. Ligand gated Ion channels-
    DIRECT ACTION- flux ions across membrane
    Ligand bind to receptor on channel cause physical change in channel structure , allowing flux of ions across membrane
    ex: GABA (gamma-amino butyric acid)- amino acid transmitter activating Cl- channel on post-synaptic membrane
    -GABA is released and binds to Cl- gated channel (ligand-gated), causing conformational change in protein.

Transmitter reuptake pumps-, used to terminate neurotransmitter action and take neurotransmitter back into where it came from, after it was released; to be reused and restored in future

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24
Q

What is the role and function of GABA (gonna-amino-butryic acid)

A

GABA- Universal inhibitory transmitter in the brain
-Has INHIBITORY action on cells
-GABA is an example of ligand that binds to receptor (ligand-gated ion channels)
GABA (gamma-amino butyric acid)- amino acid transmitter activating Cl- channel on post-synaptic membrane
-GABA is released and binds to Cl- gated channel (ligand-gated), causing conformational change in protein. channel not activated pore is closed.
When channels are activated by GABA binding to channel, it opens pore and allows Cl- to go from outside of cell, into the cell. Cl- enters cell, creates high negative charge inside cells, causing Hyperpolarization which moves it further away from the ability to dishcharge action potentials

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25
Q

Describe the action of second messengers like cyclic AMP

A

Second messenger action
Cyclic AMP: has many functions; can change responsiveness of cell to second transmitter;
activation of Phospholipase c , which converts phospholipase to IP3 (another second messenger) , affecting the excitability of cell; whether stimulating or inhibiting.
glutamate -amino acid transmitter
bind to channel and allow for transmission of Na+ ions across membrane. Sodium ions would depolarize membrane and move it closer to excitability threshold

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26
Q

What is an example of another amino acid transmitter? How does it differ from GABA?

A

Glutamate - amino acid transmitter that
binds to channel and allows for transmission of Na+ ions across membrane.
Sodium ions will Depolarize membrane and move it closer to excitability threshold
(GABA does opposite, hyperpolarizing membrane (due to Cl-)

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27
Q

what are the cellular elements of the nervous system?

A

Neurons and Glial cells.
Neurons-> cells-> Circuits-> Networks

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28
Q

How can you characterize the properties of individual neurons?
What is one major characteristic about neurons?
How does this relate to a rat and its whisker system?

A

Anatomical , biochemistry (what transmitters are produced) , physiology (whether excitatory or inhibitory neurotransmitter will be released)
sensory neuron- what kinds of shapes or colors might it respond to
Molecular level- what drives protein synthesis of this cell from an other neuron
- individual neurons form circuits (they do not operate alone
-circuit in cerebral cortex of rat brain - portion of cortex that processes sensory info from periphery
-slab of sensory cortex that responds by moving whiskers to capture information about its environment (how big is space he’s in, if wall is present) whisker system for rodent is sensitive, and their primary mode of navigating the world.
these cells constitute circuit, code information from single whisker
circuit is part of larger network
-defined number of whiskers in rows and columns
info transferred from sensory array of whiskers to transgeminal complex, transfers it to thalamus, give rise to cells in cortex and Locus Coeruleus
-network of cells and connections that inform rat about position of whisker.
rat has info about periphery, which informs rat about its behavior (change its position )

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29
Q

discuss how the different levels of complex nervous system that occur for transfer of sensory information

A

you can initially think of transfer of sensory info between cells; but cells can combine and be in circuits. Circuits can also be part of larger networks that give rise to behavioral changes

30
Q

what kind of neurons are seen in the cerebellum? what is the role and function of cerebellum?

A

-purkinje neurons-
-cerebellum- allows our brain to unconsciously control our motor activity
ex play basketball, play piano)
purkinje neurons have dendritic trees
-many dendrites to allow a great number of contacts into neuron

31
Q

Describe the anatomy of the cerebral cortex, brain stem and cerebellum.
What are mossy fibers and climbing fibers used for?
COME BACK TO THIS

A

cerebral cortex on top. Brain stem leads to spinal cord, cerebellum sits on top of brain stem
inputs up to cerebellar cortex, up to purkinje cells output to nuclei to regulate our movements
-geometrically redundant in cerebral cortex
-mossy fibers and climbing fibers move up to granular layer (of cerebral cortex) transfer info to granular part, which ascends, axons bifurcates.

32
Q

How many inputs can purkinje cells receive?
what are the role of Golgi cells, basket and stellate cells?

A

every purkinje fiber can receive 200,000 different inputs
basket and stellate cells modify electrical activity
Golgi cells- modify granular cell activity
-purkinje cells output a code for the cerebellum to carry out movement

33
Q

How may release of Norepinephrine influence brain activity for movement?

A

release of NE into circuit may allow brain process more info more rapidly for the necessary action

34
Q

what are the major parts of the brain on exterior surface?

A

Major parts of the brain:
cerebral cortex- dominant part of brain
Cerebrum
cerebellum- on top of brain stem
brain stem (from base of cortex and connects to spinal cord)

-Spinal cord- pathways ascending form periphery and descending to control movement.

35
Q

what brain structures are seen in lateral view vs dorsal view?

A

Lateral view of brain- Cerebrum, cerebellum, and brain stem
dorsal part of brain-(top down) right and left hemispheres divided by a sulcus

36
Q

what is the most developed part of human brain? what are features of both cerebrum, cerebellum and brain stem?

A

Cerebrum- MOST DEVELOPED part of human brain; spherical appearance. It is separated by LONGITUDINAL FISSURE on two brain hemispheres (cerebral hemispheres) left, and right; which the surface is uneven, has many folds
cerebellum- Ventrally to brain hemisphere and POSTERIOR part of brain; has multiple fine folds
-Brain stem- MOST VENTRAL part of the brain that continues into spinal cord

37
Q

What is the role of Thalamus?

A

Thalamus- serves as part of relay station between periphery to the cerebral Cortex (vice versa)
hypothalamus is below thalamus

38
Q

Discuss the components of the brain stem when viewing the saggital system. what is the corpus collasum and septum pellucidum?

A

Brain stem- the stem that the cerebrum resides on; part of brain that is covered and buried inside cerebral hemispheres
brain stem includes:
MIDBRAIN, PONS, and MEDULLA(medulla oblongata) that can only be visualized upon brain dissection along Saggital plane that cuts Septum Pellucidum and Corpus Callosum
septum pellucidum- a thin membrane that separates lateral ventricles
corpus callosum- a bundle of axons that connects two hemispheres

39
Q

Define what a nucleus is, including its features and functions. Also discuss role of nuclei in the brain.

A

Nucleus- a group (constellation) of neurons that are located in a specific region of the brain’s white matter, generally have appearance of grey matter, RECEIVE information from similar sources, and project their axons to similar targets.
-Nuclei belongs to grey matter structures like the Cortex. They form extensive afferent and efferent projections between each other and cerebral cortex

40
Q

What are tracts? What is the role of relay nuclei in the brain and where are they located?

A

Tracts- targeted projections
Relay nuclei- (signal sorting stations) - an assembly of second order sensory or motor neurons that connect upper neurons and spinal cord neurons.
these relay nuclei are mostly located in the BRAINSTEM

41
Q

Describe the function of the frontal and occipital parts of the brain that can be seen in saggital view.

A

saggital view of brain you can see:
frontal- EXECUTIVE FUNCTION of the brain; helps us make decisions, know what is happening around us, make judgements
Occipital- VISUAL portion
*brain is more than cerebral cortex; has deep structures with different functions

42
Q

What are the roles of white parts of brain and dark areas of brain and deep structures in the brain?

A

white matter- carry information to and from cerebral cortex and to and from brain
dark areas -accumulation of neuron cell bodies
deep structures- nuclei- cluster of cell bodies with multiple different functions

43
Q

What is the fornix and where is It located in the brain (coronal section) ?

A

Fornix- body of hippocampus
within brain, there are 3D structures
and if you look at slab of brain see structures in multiple positions

44
Q

Describe how sensory information ( touching a feather) is transferred from the finger tip all the way to cerebral cortex in the brain

A

transfer of information from fingertip all the way to cerebral cortex:
The destination for ascending sensory information- post-central gyrus

in finger tip: touch something sharp, the information will transfer as a proprioceptive sensation in cerebral cortex.
sensory neuron that has process activated by light touch of object. The info Is transferred through dorsal columns; the axons ascend all the way up to medulla and a synapse is made’
the neuron gives rise to axon which travels across medulla and takes up vertical position of fibers which ascend to medulla into pons. Now bundle of fibers turn its position
as ascend further into midbrain and fibers more laterally into thalamus(through midbrain, pons, thalamus)
next synapse will be at thalamus
then synapse at cells and ascend onto cerebral cortex on post-central gyrus
The sensory info it sends from finger tip all the way to brain stem, medulla on same side of body,
the next axon crosses midline, and sensory info ascend on opposite side of where stimulus it occurred
EX:
left finger tip, information arise on right cerebral cortex.

summary: touch a light feather activates process by sensory neuron. then axons ascend to medulla where synapse is made and the sensory information is transferred from finger tip to brain stem, medulla, midbrain, pons and thalamus all the way to cerebral cortex. Synapse at level of spinal cord. next axon crosses midline and ascends on outer side of medulla, to pons, and then ascend to thalamus another synapse and then to cortex

45
Q

Describe how sensory information of touching hot flame or object is transferred to cerebral cortex.

A

touching a hot flame- information synapse at spinal level (from midbrain, pons, thalamus, to spinal cord) and axon will cross midline and ascends to outer side of medulla to pons
it will then associate Itself to other pathways and ascend to thalamus, then to cortex
this pathway is a three cell chain- delivering info about heat from finger to cortex
* The sensory info from left finger tip (about hot object) makes its way to right cerebral cortex

46
Q

Why must neurologists know pathways of sensory info travels to cortex and other parts of brain

A

Neurologists need to know this pathway:
knowledge of pathway and where it passes is important
By simple testing of touching locations and parts of body you could determine level of lesions in pathway
knowledge of where fibers are crossing, interruption of information will allow you to localize it to other side of body.
two different kinds os sensory info are terminating in same location, they follow different trajectory up to cortex(where info is processed)

47
Q

How does the transfer of sensory information from different parts of the body to cerebral cortex differ?

A

transfer info from head and face up to cerebral CORTEX - travels through trigeminal sensory center; has different relays: info temp sensitivity, : touch
ultimate destination: thalamus - final relay to
transfer of sensory info for every body parr from neck upward- ascends through TRIGEMINAL sensory system
Transfer of info for everything downward- climbs Spinal Cord through sequence of different synapses

48
Q

spinal cord reflex in response to touching sharp object

A

step on sharp object, the info ascend into spinal cord, and ascending connections will inform you that you’ve stepped on something sharp
before that occurs: you have a
series of synapses that occur, causing you to lift your leg and inhibit extensor muscle and activate flexor muscle to lift up leg
meanwhile for balance and support while lifting leg sensory information was conveyed to opposite leg to relax flexor muscle and contract extensor muscle.
you do not need to engage rest of brain because there are complex circuits built into spinal cord to control this

49
Q

Describe what occurs in spinal cord reflex in response to stepping on a sharp object?

A

step on sharp object, the information will ascend into spinal cord, and ascending connections will inform you that you’ve stepped on something sharp
before that occurs: you have a
series of synapses that occur, causing you to lift your leg and inhibit extensor muscle and activate flexor muscle to lift up leg
meanwhile for balance and support while lifting leg sensory information was conveyed to opposite leg to relax flexor muscle and contract extensor muscle.
you do not need to engage rest of brain because there are complex circuits built into spinal cord to control this

50
Q

What happens in the pathway when initiating a movement?

A

To initiate movement:
pre-central gyrus- source of commands of primary motor cortex to make a command
you have a cluster of neurons that give rise to information descending through midbrain (cerebral peduncles) , pons, and medulla (pyramid) onto spinal cord, where there is a synapse that occurs to cluster of motor neurons that activate muscles that gives rise to movement
ex: playing a piano
if interruption on function here, deficit will be on opposite side of body
electrical potential- small portion in human brain; direct contact between membranes (no use of synaptic cleft) electrical potential transferred directly through membranes

51
Q

What are the steps in chemical Neurotransmission?

A

Chemical Neurotransmission:
1. Action potential reaches axon terminal
2. calcium channels open (causes by change in membrane potential)
3. Calcium causes vesicles to release neurotransmitter
4. Neurotransmitter crosses synapse
5. Neurotransmitter binds to neuroreceptors
6. Trigger signal in post-synaptic neuron

52
Q

Describe the mechanism of Neurotransmission. Also discuss the differences between depolarization, hyperpolarization and graded response .

A

Mechanism of Neurotransmission:
1. Action potential produces rapid calcium entry at nerve terminal
2. Rapid fusion of vesicles (with membrane in post-synaptic terminal)
3. Diffusion of neurotransmitters across synaptic cleft
4. Binding to post-synaptic receptor
5. change in membrane potential
a. Depolarization- REDUCTION of membrane potential sufficient to initiate an action potential
b. Hyperpolarization- INCREASE in membrane potential (like GABA, cl- makes membrane negative and moves cell further away from exciting cell)
c. Graded Response- REDUCTION of membrane potential NOT sufficient enough to initiate an action potential (partially depolarizes and hyper polarizes)

53
Q

What are the guidelines for defining when a substance is a neurotransmitter?

A

Guidelines for defining when a substance is a neurotransmitter:
1. Must be present in neurons together with the enzymes involved in synthesis
2. Released from nerve terminals following depolarization in a calcium dependent process
3. Activates specific post-synaptic receptors causing depolarization or hyper polarization of the postsynaptic membrane
4. Produces the same effect when applied microiontophoretically as when released physiologically (if not activating axon itself, you can apply the transmitter from outside nervous system)
5. Blocked by specific antagonists
6. Action is terminated by a specific mechanism
7. Activates specific presynaptic auto receptors which usually reduce its release thereby regulating its concentration in synapse.

54
Q

what occurs at an electrical potential ?

A

electrical potential- small portion in human brain; direct contact between membranes (no use of synaptic cleft) electrical potential transferred directly through membranes

55
Q

Describe the biochemical pathway for catecholamine synthesis . How do you differentiate whether cell is dopamine or Norepinephrine?

A

Pathway for Cathecholamine synthesis:
Catecholamines include dopamine and Norepinephrine (prominent in Brain)
process:
1. Tyrosine is converted to DOPA by enzyme tyrosine hydroxylase (adds OH group)
2. DOPA converts to Dopamine by enzyme aromatic amino acid decarboxylase (removes COOH group)
3. Dopamine converts to Norepinephrine ascorbate by enzyme dopamine beta-hydroxylate (adds OH group)
if cell has Dopamine beta hydroxylase enzyme, it is a Norepinephrine cell
if it does NOT have this enzyme dopamine is the transmitter
(if you add methyl group to NE you get epinephrine)

56
Q

discuss the Classes of neurotransmitters and the different categories that are included

A

Classes of Neurotransmitter:
1. Small molecules
a. Acetylcholine (ACh)
b, Amino acids
- Glutamate (GLU) (excitatory )
-Gamma-aminobutryic acid (GABA)
- Glycine (Gly)
-GABA and glycine are inhibitory in brain and spinal cord
c. Monoamines (single amine group on neurotransmitter)
i.Catecholamines
a. Dopamine (DA)
b. Norepinephrine (NE)
c. Epinephrine (EPI)
ii. Indoalmines
a. serotonin (5- HT)
iii. imidazoles
a. Histamine (HIS)

  1. Peptides - short amino acid chains; numerous throughout brain (endorphins, angiotensin Substance P, CRF, Hypocretin/Orexin, Oxytocin)
  2. Dissolved Gases (ex: NO, CO)
    NO can pass through membrane
57
Q

Which neurotransmitters fall into the category of fast and slow receptors in the Human brain ?

A

FAST Ion Chanel linked receptors (Ionotropic) :
1. Excitatory
-Cholinergic nicotinic
-Glutamate/Aspartate
-5-HT3
2. Inhibitory
-GABA A
Glycine

SLOW G protein linked receptors (metabotropic)
-cholinergic Muscarinic
-Adrenergic (alpha1, alpha2, beta1, beta 2)
these are Norepinephrine systems
-GABA B
-Dopamine (D1-like, D2-like)
-Histamine
-5 HT-1A, 5 HT-1B, 5 HT-1d, 5HT-2A, 5-HT 2C
-Peptide receptors (ex; angiotensin II, cholecystokinin, neuropeptide-Y, somatostatin, opiate, Substance P, Vasopressin)

58
Q

provide the molecular explanation of neuromodulation of GABA by Norepinephrine. How can the second messenger cAMP enhance GABA function?

A

there is a phosphorylation site on intracellular channel .
cl- channel Opening can be regulated by phosphorylation site which is regulated by sequence of actions initiated by NE (activate adenylate cyclase and cause formation of second messenger cAMP)
cAMP can activate protein kinase. Protein kinase will cause phosphorylate of site on protein
if cell receive inputs of GABA and it binds to receptor ; meanwhile NE was released which produces phosphorylation of site, the phosphorylation would amplify channel opening and allow more Cl- ions to flow through stronger than if site not phosphorylated .

59
Q

Differentiate between inotropic and metabotropic receptors

A

Inotropic- Direct gating, Fast process
- Ion channels, ligand gated channels
where ligand binds to receptor for activity
Metabotropic- Indirect gating ; Slower process, G-protein coupled receptors, using second messenger, series of steps for action (adenylate cyclase, cAMP)

60
Q

What is the theory of Co-transmitter release.

A

Co transmitter release-
neuron synthesizes small molecule transmitters and peptides that are co-localized in synaptic ending
so transmitters like GABA can be released with co-peptide and the
same for catecholamines are found. Catecholamines can have different peptides and have option of
only catrcholimaine being released or catecholamine and peptide is released for impact on post-synaptic membrane

61
Q

what are the long term changes in synaptic transmission?

A

Long term changes in synaptic transmission:
1. SENSITIZATION- decreased neurotransmitter levels result in increased receptor numbers leading to increased response
2. DESENSITIZATION- Increased neurotransmitter levels result in Reduced receptor numbers leading to reduced response
3. Plasticity- strengthening of synaptic connections that may allow for memory formation or recovery of function after injury.
(synapse change responsiveness to transmitters)

62
Q

Describe the different ways neurotransmitters can be terminated

A

Termination of Action:
1. Degradation/recycling by specific enzymes
a. Acetylcholinesterase (AChE) for AcH
b. Monoamine Oxidase (MAO) for monamines
c. Catechol-O-methyl transferase (COMT) for catecholamines
2. Reuptake by high affinity membrane transporters (pump excess transmitter into post-synaptic cell for reuse)
ex; glutamate, GABA, glycine, serotonin, dopamine, norepinephrine (Very common way)
3. Diffusion (removal by extracellular peptidases)
-Slower process
(peptidases break down peptides, and diffuse into extracellular space)

63
Q

Discuss ways of how drugs can interfere with synaptic transmission

A

Effects of Drugs on Synaptic Transmission
A. presynaptic
1. Block reuptake (ex: antidepressants) (try and boost amount of neurotransmitters)
2. Change precursor availability (ex: L-DOPA)
3. Inhibit neurotransmitter synthesis (ex: cardbidopa- false substrate of DOPA)
4. Inhibit storage of neurotransmitter synthesis (ex: reserpine) (less transmitter for release
5. Alter release of neurotransmitter (ex: amphetamine)
6. Provide presynaptic regulation through auto receptors
7. provide presynaptic regulation through heteroreceptors
B. Postsynaptic
1. Agonists bind to receptor and produce response
2. Antagonists bind to receptor and reduce or inhibit response
3. Receptor adaptation- repeated doses of drugs lead to long term changes in receptor number and affinity resulting in sensitization or desensitization
C. Enzyme Inhibition of degrading enzymes increases amount of neurotransmitter in synapse:
MAO inhibiters such as Pargyline or AChE inhibitors such as Tacrine or Mestinon

64
Q

Discuss the drugs or toxins that enhance or Depress transmission

A

Drugs or Toxins that Enhance Transmission:
1. By enhancing synthesis or packaging neurotransmitter:
1.L-dopa crosses the blood-brain barrier and is metabolized into dopamine, compensating for lower dopamine levels in Parkinson’s disease
2. by enhancing neurotransmitter release: Amphetamine causes increased release of Norepinephrine and dopamine, acts as a stimulant
3. By effects on neurotransmitter-gated ion channels;
Benzodiazepine tranquilizers (diazepam, or Vallium) increases frequency of opening of GABA-gated Cl- channels
Barbiturate sedatives increase the duration of opening of GABA- gated Cl-channels
4. By effects of G-protein coupled neurotransmitter receptors: Morphine mimics opioid peptides, binds to their receptors, causes analgesia and other effects
5. By Blocking removal of neurotransmitter: fluoxetine (Prozac), an antidepressant blocks serotonin reuptake
Cocaine blocks reuptake of NE and dopamine
6. By blocking degradation of neurotransmitter: Pyridostigimine (Mestinon) blocks acetylcholinesterase, Is used to treat patients with myasthenia gravis
7. By blocking retrograde signaling: caffeine blocks presynaptic adenosine receptors, prevents suppression of transmitter release, acts as stimulant

Drugs or Toxins that DEPRESS Transmission
1. By interfering with synthesis of packaging of neurotransmitter: Vesamicol or reserpine back transport of Acetylcholine and amines, respectively into synaptic vesicles
2. By interfering with neurotransmitter release, Botulinum toxin blocks release of acetlycholine, causes flaccid paralysis
-tetanus blocks the release of glycine, causes rigid paralysis
3. By effects of neurotransmitter gated ion channels: Strychnine blocks glycine-gated Cl-, causes convulsions and other signs of hyperexcitabiltiy
-Phencyclidine (PCP, “angel dust) blocks NMDA receptors
-Curare (arrow tip poison) blocks skeletal muscle nicotinic receptors, causes paralysis
-Hexamethonium blocks autonomic nicotinic receptors
4. By effects on G-protein-coupled neurotransmitter receptors: Haloperidol (Haldol), an antipsychotic, blocks some dopamine receptors
-Atropine blocks muscarinic acertycholine receptors, causes automatic changes

65
Q

Discuss the pathways in the brain that utilize different neurotransmitters

A

Dopamine pathway;
-arises from clusters of cells in the brain stem and projects to cortex in forebrain
Acetylcholine pathway; arises from cluster of cells and projects through cerebral cortex
Norepinephrine arises from Locus cerroleus and then gives rise to projections in cerebellum and then to cerebral cortex
Serotonin- arises from cells in dorsal rafae, and innervate cerebellum, cortex and other forebrain structures

The NE, Serotonin and Acetylcholine pathways are BROAD

66
Q

Discuss the treatment strategy for Parkinson’s disease
REVIEW

A

Treatment Strategy for Parkinson’s disease
-enhance the synthesis of L-DOPA (precursor), so that it will convert into Dopamine and compensate for lower dopamine levels in Parkinson’s disease

67
Q

Discuss the treatment strategy for Anxiety
REVIEW

A

Treatment strategy for Anxiety:
increase amount of GABA so it can bind to Ativan receptor, causing change in shape of receptor, allowing ions to easily pass through channel
-Receptor modulation increases synaptic efficacy
GABA will help reduce stress and calm a person down

68
Q

what are the treatment strategies for Depression?
REVIEW

A

Original Treatment Strategy for Depression
-Block the reuptake of Monoamine inhibitor (Pargyline) that inhibits the production of neurotransmitter
this will increase Norepinephrine levels. helpful since NE provides alertness and energy (help with depression, stay alert)
Additional treatment strategy for Depression:
Prozac blocks reuptake of serotonin , increase 5-HT to bind to receptor. More serotonin will keep someone happier, stable, feel more focused
low serotonin levels -lead to depression

69
Q

Discuss the treatment strategy for Alzheimer’s Disease
REVIEW

A

Treatment Strategy for Alzheimer’s Disease
Block the function of AChE inhibitor called Tacrine (prevents normal break down ACh), allowing more ACh to be made
beneficial as low levels of ACh associated with Alzheimer’s

70
Q

Discuss the treatment strategy for Schizophrenia
REVIEW

A

Treatment Strategy for Schizophrenia
- Haldol blocks dopamine receptor, allowing low levels of Dopamine to be made
High levels of dopamine associated with schizophrenia
Receptor antagonism (reduce response of dopamine )

71
Q

Discuss the treatment strategy for Substance Abuse
REVIEW

A

Treatment Strategy for Substance Abuse:
cocaine blocks the reputake of Dopamine. Block Cocaine’s function, allowing reuptake of Dopamine. It allows Dopamine to be more available