Cell and Molecular Neuro Flashcards

1
Q

Neurophysiology

A

Branch of physiology abd neuroscience concerned with function of the nervous system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Significance

A

As chiropractors we affect the nervous system with each adjustment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where in the spine are sensory receptors?

A

Everywhere including the outer 1/3 of the vertebral disc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Injured state resulting in sensitization of nociceptors

A

Can result from major trauma or repetitive microtrauma. Results in sympathetic hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

During an adjustment what happens to mechanic receptors?

A

Stimulate Joint mechanoreceptors, which can potentially decrease nociceptive activation

In other cases may contribute to sensitized state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Classes of neurons

A

Multipolar
Psuedouniploar
Bipolar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Multipolar Neuron

A

has a single axon and contains multiple dendrites extending from the soma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Psuedounipolar/unipolar

A

Contains a single process extending from the soma that can branch to form dendrites and axon terminals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Bipolar neuron

A

Contains two processes, One axon and one dendrite extending from the soma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CNS Terminology

A

NUCLEI - refers to neuron cell bodies that are morphologically distinct
TRACTS - refer to multiple axonal processes that are morphologically distinct in a bundle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PNS terminology

A

GANGLIA - refers to multiple neuron cell bodies

NERVES - are multiple axons in a distinct bundle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Reticular Theory

A

Outdated Theory by Camillo Golgi

Neurons are connected to neighboring neurons through protoplasmic links
Neurons linked together forms continuous nerve cell network or “reticulum”
Information may flow in any direction within the network

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

(Main Ideas of) Contact Theory

A

Argued against Reticular Theory (By Santiago Ramon y Cajal)

Neurons are distinct cells
Neurons communicate with each other at distinct points of contact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

5 principles of Contact Theory

A

1) Neuron is the elementary structural and signaling unit of the nervous system
2) Information is recieved at a receptive point of a neuron and travels in a unilateral direction along the axon to the terminal LAW OF DYNAMIC POLARIZATION (specialized areas for receiving and sending)
3) The axon terminal of one neuron is in close proximity with the receptive region of another neuron at a specialized junction called a synapse
4) An individual neuron will only communicate with synaptic contacts on specific portions of a neuron. Connection between neurons are not random, neuronal circuits pass information through specific pathways. Concept is CONNECTION SPECIFICITY
5) Connections between neurons can be modified by experience, either through strengthening or weakening of synapses. Makes brain function more efficient. SYNAPTIC/NEURAL PLASTICITY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Electrophysiology

A

Can provide a detailed picture of the events taking place at the individual cell level.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Digital Cathode Ray Oscilloscope

A

A lab instrument that provides accurate time and amplitude measurements of voltage signals over a wide range of frequencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

CRO Macroelectrodes

A

Measure the activity of a population of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

CRO Micro-electrodes

A

Can be placed in or near a single cell to measure that cells electrical activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Population (Global) recording

A

Utilizes macro-electrodes
Measures voltage
EEG (for the cortex)
EMG (muscles)
ERP (specific sensory pathway) activity of the brain in response to a stimulus
Whole nerve (Peripheral nerves)
Excellent temporal resolution, poor spatial resolution

Clinical assessment (provides us with knowledge of whether or not there is a problem)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Single Cell Recording

A
Utilizes Micro-electrodes
Measures Ion current and voltage
Resting Membrane Potential
IPSP, EPSP
AP
Intracellular (in Vito, in vitro)
Extracellular (in vivo)
Patch clamp (in vitro)

Experimental method

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Neural connection properties

A
Electrical 
Unique to excitable cells
Very fast
Only the plasma membrane is involved
ATP-dependent
Signaling is directly and indirectly coupled to all cellular biochemical process by ion channels and numerous signal transduction pathways (STPs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Membrane voltages

A

Graded (EPSPs, IPSPs) or All or None (AP)

Graded potentials occur at dendrites and the soma

AP are initiated at a region adjacent to the axon hillock and travel along the axon to the terminal button

Both rely on activity of ion channels located throughout the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

ERP

A

Measuring activity in a sensory pathway
Visual (Flash, Pattern)
Auditory (Click, Tone)
Sensory (Light touch, Pressure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Three techniques of Single Unit Electrophysiology

A

Extracellular: Voltage measurement taken outside of the cell, which records all-or-none action potentials

Intracellular: Voltage measurement taken inside of the cell which records Resting Membrane Potential, graded potentials, and APs

Patch Clamp: Records ionic current (not voltage) of either a single or a group of ion channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Resting Membrane Potential

A

Allows the membrane to be in a “ready state”. All electrical activity results from a change to this potential.

-70mV (between -40 and -90 mV dependent on size)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Ionic basis of the Resting Membrane Potential

A

Neurons exist in an aqueous environment with + and - ions.
Ion species will attempt to achieve their own equilibriums.
The charge built up across the membrane at rest results from the differential distribution of the ion species.
More negative ions on the inside than on the outside.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Ion distribution in a neuron at rest

A

More Na+ and Cl- ions are found on the outside of the neuron

More K+ and negatively charged ions are found on the inside of the neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Homogenizing factors across the neural membrane

A

Random motion (concentration gradients)

Electrostatic pressure (like charges repel and opposite charges attract)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Chemical synapses

A

Allow for cell to cell communication via the release of chemical agents (neurotransmitters) by presynaptic neuron.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Neurotransmitter release

A

Released from synaptic vesicles from the Presynaptic axon terminal
Released synaptic cleft

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Three types of chemical synapses

A

Axodendritic - most common. Synapse on dendrite of postsynaptic neuron.

Axosomatic - synapse on the soma

Axoaxonic - synapse on the axon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Properties of electrical synapse

A

3.5nm synaptic cleft with a 10-100 usec delay. Near instantaneous signaling.
Some synaptic plasticity but no amplification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Properties of chemical synapse

A

20-40nm synaptic cleft. 1-5msec delay.
Provides temporally and spatially focused transmission. Provides alterations in synaptic core goth efficiency.

Synaptic plasticity and signal amplification.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Chemical synapses divided by distance

A

Directed - neurotransmitter release site and reception site are in close proximity.
Non-directed - release site is at a distance from reception site.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Neuromuscular junction

A

Chemical synapse between extramural and intramural muscle fibers of striated and skeletal muscle.

All NMJs utilize acetylcholine (ACh)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Motor unit

A

One alpha neuron and all extramural muscle fibers innervated by its axon (branches at its terminal end.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Nicotinic ACh receptor

A

Large protein consisting of 5 subunits. Alpha subunit contains an ACh-binding receptor.
Central pore functions as a passage for Na+ ions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

CNS chemical synapses properties

A

Multiple transmitter ligands. Graded response consisting of EPSP and IPSP. Summation is necessary. Receptors may be ionotropic or metabotropic.
Presynaptic inhibition or facilitation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Properties of NMJ (PNS chemical synapses)

A

Single transmitter ligand. End Plate Potential (depolarization only). Only excites target. Only ionotropic receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How are postsynaptic potentials generated?

A

Binding of neurotransmitter on receptor causes the opening of ion channels and can induce depolarization or hyperpolarization.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Depolarization

A

Bringing membrane potential closer to threshold of excitation (EPSP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Hyperpolariztion

A

Makes the membrane potential more negative. IPSP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Properties of EPSPs/IPSPs

A

Graded potentials with varying amplitudes. Travel passively but rapidly from site of origin. Decrease in amplitude as they travel along the axon (decremental)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Generation of AP

A

Sum of IPSPs and EPSPs must be sufficient to reach the threshold of excitation
-55mV to generate an AP

Generated in the region adjacent to the axon hillock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Features of an AP

A

Momentary reversal of membrane potential from - to +
All or none response
Directly related to the concentration of Na inside and outside the cell

Voltage gated ion channels mediate the production and conduction of APs by altering the membrane potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Two types of summation

A

Spatial - Multpile PSPs from different synapses are combined to form a a larger PSP
Temporal - Multiple PSP form the same synapse combine to form a larger PSP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Phases of an action potential

A
Resting state
Threshold
Depolarization phase
Depolarization phase
Undershoot
Refractory Phase
   Absolute refractory phase
   Relative refractory phase
Return to Resting State
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Resting state

A

Voltage gated Na and K ion channels are closed and leak ion channels are open. Membrane potential is a RMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Threshold

A

One or more excitatory potentials (EPSPs) opensomevoltage-gated Na ion channels. When the threshold is reached, more Na+ ion channels will open and an action potential is triggered.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Depolarization phase

A

With Na ion channels open, Na ions continue o rich into the cell, which alters the membrane potential.
K ion channels are still closed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Repolarization phase

A

Voltage gated ion channels become INACTIVE while K ion channels begin to open.
K ions rush OUT OF the cell to change the membrane potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Undershoot

A

Na ions channels are closed and K ion channels are closing but slowly K ions are still leaving the cell through the remaining open channels. Making the membrane potential more negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Refractory Period

A

in the wake of the AP, Na ion channels are deactivated for a brief time. Makes it difficult for the neuron to produce an AP.

Absolute Refractory Period - from initiation of AP to immediately after the peak. Cannot lead to another AP.
Relative Refractory Period - following absolute refractory period. Na channels begin to recover from inactivation. A stronger than normal stimulus is needed to elicit an action potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Return to Resting State

A

The RMP of the neuron is restored as all K+ ion channels close and the Na/K pumps work to re-establish baseline concentration of these ion channels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Anti-Homogenizing factors across cell membrane

A

Neural membrane has different permeability to ions
passive property as it uses ion channels. K+ and C- can pass through the membrane. Na+ moves through with difficulty and (-) ions cannot move through at all.

Membrane bound transporters that consume energy.
Na-K pump that exchanges 3 intracellular Na+ ion for 2 extracellular K+ ions. MAJOR factor in maintaining the differential ion concentrations,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Cl- ions in the neuron

A

Can readily diffuse across membrane. Negative internal potential drives Cl- ion s out of the neuron. As the ions accumulate outside the cell the concentration gradient pushes them into the neuron.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Na+ ions

A

Has difficulty diffusing across the membrane. Tend to move into the cell due to their high extracellular pressure and negative charge of internal neuron. Na-K pump moves the Na out of he cell at the same slow rate that they enter the cell (maintains -70 mV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

K ions in the neuron

A

neural membrane allows K+ ions to readily diffuse. Moves out of cell due to high internal concentration. Internal negative pressure moves ions back into the cell. Na-K pump maintains charge by moving K ions into the cell at the same rate that they leave.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Two types of ion channels

A

Leak (non-gated) ion channels

Gated ion channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Non-gated ion channels

A

open even in a resting state
selective for a single ion species
contributes to RMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

gated ion channels

A

closed until opened by a stimulus
can be selective for one or multiple ion species.
Necessary for graded or all or none potentials and neurosecretions. (depolarizing and hyperpolarizing effects)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Location of ion channels

A

Leak channels: cell body, dendrites, axon
Ligand gated channels: Cell body, dendrites
Voltage gated channels: Axon Hillock region, Axon, axon terminal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Electrical synapses

A

Allow for direct cell to cell communication via the flow of electrical current through specialized membrane channels that connect the two cells

64
Q

Conduction of action potentials

A

APs are nondecremental and can travel in either direction though under normal physiological conditions they travel in one direction. Conducted slower than postsynaptic potentials.

65
Q

Conduction speed of AP is dependent upon…

A

Myelination - myelinated axons travel faster

Diameter - large diameter axons conduct faster than smaller ones

66
Q

Defining criteria of Neurotransmitters

A

Presynaptic presence (enzymes and precursors may be used as evidence)

Must be released in response to presynaptic depolarization. release must be Ca dependent. Selective stimulation can be difficult and removal occurs quickly at the cleft.

Specific receptors must be present on the postsynaptic membrane

67
Q

Categories of NT

A

Large-molecule: Neuropeptides only

Small-molecule: 4 classes including amino acids, monogamies, actylcholine, and unconventional NT’s

68
Q

Small molecule NT

A

AA NT - Glutamate, Aspartate, Glycine, GABA

Monoamine - slightly larger than AA - Dopamine, Epinephrine, Norepinephrine, Serotonin

acetylcholine - add an acetyl group to a choline molecule. Main NT at NMJ. Also found in synapses of ANS and CNS

Unconventional NT - some are soluble gases - Nitric Oxide, Carbon Monoxide. Produced in neural cytoplasm and diffuse through the cell membrane to nearby cells then stimulate 2nd messenger cascades.
Endocannabinoids - similar to THC. Produced immediately before release. Affect presynaptic neurons through inhibition of synaptic transmission

69
Q

Large-molecule NT

A

Tend to modulate slower ongoing synaptic functions
Neuropeptides. Short proteins, and can act as hormones.
Pituitary peptides
Hypothalamic peptides
Brain-gut peptides
Opoid peptides
Misc. peptides

70
Q

Axonal Transport, Synthesis, Packaging of Small Molecule NT

A

Synthesized in the cytoplasm of the presynaptic terminal button. Enzymes needed for synthesis are produced in the cell body and are transported along microtubules to the axonal terminal via slow axonal transport.
Precursor molecules are taken into the terminal by transporter
Packaged into small, clear core synaptic vesicles by the Golgi complex within the terminal button.

71
Q

Axonal Transport, Synthesis, Packaging of Large Molecule NT

A

Synthesized in the cytoplasm of the cell body on ribosomes
Packaged into large, dense core synaptic vesicles by the Golgi complex in the cell body
These vesicles are transported along microtubules to the presynaptic terminal button via fast axonal transport

72
Q

Co-existence of NT

A

Many neurons synthesize and release two or more different neurotransmitters. Low frequency stimulation will release small molecule NT and high frequency stimulation is required for the release of neuropeptides.

73
Q

Release and recycling of NT molecules

A

There are mechanisms for releasing and recycling NT most of which are dependent upon Ca. Exocytosis and endocytosis follow each other in a rapid and constant fashion. Continuous release of NT if necessary.

74
Q

Synaptic Vesicle Cycle

A

NT molecules are packaged into synaptic vesicles at the presynaptic terminal.

Vesicles congregate near docking sites of the presynaptic membrane called “active zones”. Vesicles are anchored in place near the active zones by synapsins.

During an AP, the membrane is depolarizer, causing these ion channels to open allowing an influx of Ca+ into the terminal

This Ca+ influx leads to the phosphorylation of the synapsin proteins

Phosphorylation of synapsins readies vesicles of exocytosis by allowing them to dock at the presynaptic membrane facing the synaptic cleft, fuse with it, and release their transmitters into the synaptic cleft

Synaptic vesicles and/or membrane components are then rapidly retrieved (endocytosis)

Vesicles are recycled and re-filled with NT and are readied for re-release

75
Q

Vesicle release is directly related

A

Related to the level of the Ca within the terminal

76
Q

Ca level and Small NT

A

Small molecules are often released in a pulse each time an AP triggers a Ca+ ion influx.
Low frequency stimulation often only increases the Ca concentration near the membrane which favors the release of small molecule NT

77
Q

Neuropeptides and Ca level

A

Neuropeptides are released gradually as teh level of intracellular Ca ions
High frequency stimulation leads to a more general increase in Ca which will release both small molecule NT and neuropeptides

78
Q

Importance of voltage gated Ca molecules

A

Amount of NT released is very sensitive to the exact amount of Ca that enters
Blockage of voltage-dependent ca channels results in elimination of NT release as well as a postsynaptic response
Micro-injection of Ca into the presynaptic terminals can trigger NT release in absence of an AP

79
Q

small molecule NT Binding Patterns

A

Activate either ionotropic or metabotropic receptors

Function to transmit rapid or brief excitatory or inhibitory signals

80
Q

Large Molecule NT

A

Almost all Biden to metabotropic receptors that act via 2nd messengers
Function to transmit slow and long lasting signals

81
Q

Activation of receptors by NT molecules

A

Basic properties - transmembrane protein with extracellular binding sites. Ligand specific.
Receptor subtypes - Different types of receptors to which a particular NT can bind to are called subtypes. Tend to be located in different brain types. Often respond differently to the same NT

82
Q

Classes of Postsynaptic receptors

A

Ionotropic - Receptors associated with ligand or voltage activated ion channels
Metabotropic - receptors associated with G-protein coupled receptors

83
Q

Ionotropic receptors

A

Often activated by small molecule NT
Binding of a NT to an ionotropic receptor causes a conformational change opening the ion channel.
Post-synaptic potential will be rapidly produced if Na channel is opened and EPSP will be produced. If a K channel of CL channel is opened an IPSP will be produced.
Direct action leads to a fast activation. Faster than metabotropic.

84
Q

Metabotropic receptors

A

More prevalent than ionotropic receptors. Can be activated by small NT or neuropeptides.
Results in activation of G-protein. Indirect action leads to slower activation. Longer lasting effects than ionotropic receptors.

85
Q

Autoreceptors

A

Metabotropic receptors located on the presynaptic membrane with a special function. Bind to their own neuron’s NT.
Thought as a homeostatic feedback system that can modulate the function of a presynaptic neuron.
Monster and regulate the amount of NT. Synthesized or released, or firing rate of the neuron.

86
Q

Ligand agonists and antagonists

A

Agonists bind to the receptor and create the same effect.
Competitive antagonists bind to the same receptor and prevents activation.
Non-competitive antagonists binds to a different site as the natural ligand and either fully or partially prevents activation.

87
Q

How to terminate synaptic messages

A

Enzymatic degradation of NT in the synapse - breakdown products are brought back into the terminal button to be recycled
Reuptake - via specific transporter protein in the presynaptic plasma protein
Passive diffusion - may be taken up by glial cells

88
Q

Intercellular chemical synaptic transmission

A

Signal = NT
Transduction receptor = NT receptor on postsynaptic membrane
Target molecule = ion channel
Response caused by ion channel = electrical response of postsynaptic cell

89
Q

Intracellular Transmission

A

Signal = NT or hormone
Transducing receptor = G-protein coupled receptor
Target molecule = 2nd messengers (Ca and cAMP) and effector enzymes
Response = physiological response and gene expression

90
Q

Signal Amplification

A

An advantage of intracellular signal transduction is signal amplification.
A single reaction creates a greater response by generating a large number of molecular products

91
Q

Control of cell behavior

A

Complex signal transduction pathways allow for precise control of cell behavior over a wide range of time
Concentration of signaling molecules must be tightly regulated. Every molecules concentration must return to baseline before the next stimulus arrives in order to ensure rapid responses.
Keeping the intermediates in a signaling pathway activated is critical for sustained responses

92
Q

Classes of 3 signaling molecules

A

Cell-impermeant molecules: Bind to extracellular receptors on the target cell membrane, short-lived due to rapid metabolism and/or endocytosis

Cell-permeant molecules: cross the plasma membrane and bind to intracellular receptors in the cytoplasm or nucleus. Tend to be insoluble and are often transported in the blood or other extracellular fluid by binding to specific carrier proteins. Unlike cell-inpermeable molecules these may persist in the bloodstream for hours or days

Cell-associated molecules: Bound to extracellular surface of the plasma membrane of the signaling cell, bind to extracellular receptors on target cells that they come into contact with.

93
Q

Cell-impermeable molecule receptors STP

A

Proteins that span entire membrane. Extracellular binding portion and intracellular signaling portion.

94
Q

Cell-permeant molecule STP

A

Intracellular proteins found in cytoplasm or nucleus.
Often bound to an inhibitory complex. Once activated the complex is removed and a DNA-binding domain is exposed.
Often activating signaling cascades that produce new mRNA and proteins within the target cell.

95
Q

General classes of GTP_binding proteins

A

Both G-protein linked receptors and enzyme-linked receptors can activate biochemical reaction cascades that modify the function of target proteins. G-binding proteins are responsible for actions in these

Heteotrimeric G-proteins: made of hop to 3 distinct subunits

Monomeric G-proteins: Made up of a single subunit (tend to be growth factors)

96
Q

Activation of a G-protein Coupled receptor

A

Regulate the gating of ion channels and alter the function of downstream molecules. Many produce 2nd messengers.
May also directly bind to and activate ion channels.

Cardiac muscle cells have G-protein-coupled receptors that bind ACh. Activation of these receptors will open K+ ion channels, decreasing contraction rate of the muscle cells, thereby decreasing HR

97
Q

Regulation of Ca concentration

A

Concentration is ordinarily much higher outside the cell than inside. Maintained by a Na/Ca exchanger and a calcium pump. Calcium is also pumped into ER and mitochondria for later use
Ca ions enter the cytoplasm via voltage gated or ligand gated channels in the plasma membrane. Other channels allow Ca ions to be released form the ER into the cytoplasm in response to intracellular signals.

98
Q

Role of Ca as a 2nd messenger

A

Mechanisms for raising and lowering concentration of Ca allows For precise control of timing and location of Ca signaling within the neuron.
Allows Ca to control different signaling events. (Rapid rise of calcium in the terminal axon results in rapid exocytosis of synaptic vesicles)

99
Q

Phosphorylation and dephosphorylation caused by 2nd messengers

A

Rapidly and reversible changes teh function of a protein.

Phosphorylation uses protein kinases and protein phosphatases.

100
Q

Nuclear signaling

A

2nd messengers can elicit prolonged effects by acting on proteins that promote the synthesis of new RNA and proteins.
Regulate gene expression by converting transcriptional activator proteins from inactive state to an active state.

101
Q

Neuroplasticity

A

The ability of synapses to alter their strength. Depends on frequency and previous activity.

102
Q

Establishing basic brain connections

A

Formation of distinct brain regions
Neurogenesis
Axogenesis: formation of axon tract
Synaptogenesis: synapse formation

103
Q

Mechanism of Neuroplasticity

A

STPs are often the mechanism by which these changes occur

Modification of intracellular Ca levels leading to gene expression (effect of 2nd messengers)

104
Q

Periods during which experience may be more pronounced

A

CRITICAL PERIODS: Time windows in which the activity mediated (environmentally) influences are essential for development
Become less effective with age.

SENSITIVE PERIODS: Windows during which the environmental activity influences brain circuitry however, to a lesser degree than during the critical period.
Major of developmental effects occur during sensitive periods

105
Q

Evolutionary perspective of Neuroplasticity

A

Once formed neuronal circuits must be used. If not used they will not survive or function.
The advantage of slow development of human brains is that it allows for acquisition of experience.

106
Q

Sensory deprivation

A

Rats raised in darkness have fewer synapses and dendritic spines in their primary visual cortex. As adults they exhibited defects in pattern vision and depth perception

107
Q

Environmental enrichment

A

Rats raised in visual complex cages were found to hav ethicker corticies with more dendritic spines and synapses per neuron.

108
Q

Effect of nature of neurodevelopment

A

Neural pathways that receive the most input form stronger connections and can potentially take over cortical regions which would have been otherwise devoted to other functions (crossmodal plasticity)

109
Q

Monocular deprivation

A

Prolonged covering of one eye will limit the ability of that eye to activate the visual cortex. The ability of the other eye is increased.
A decrease in the branching of axons of LGN neurons was found on the covered side.

110
Q

Neuroplasticity in the sensory cortex

A

Changes in the sensory input experience will result in changes of the sensory cortex to match and adapt

111
Q

Early nervous system development

A

Before the NS is fully developed neurons fire spontaneously and interact with the environment. Allows for fine-tuning while developing.

112
Q

Effects of Musical Training on the Brain

A

Increase in the size of the region of the primary somatosensory cortex devoted to the fingers of the playing hand.
Higher volume of gray matter of the hippocampus, middle and superior frontal lobes, insula, and cingulate gyrus
Left anterior hippocampus region in musicians exhibited differential activation when sound variation was detected.
Different organization of the thalamocortical network and enhanced connectivity with auditory regions and precuneus

Age of onset of training is the strongest indicator of magnitude of change

113
Q

Neuroplasticity in adulthood

A

Increase, decreases, or modification of cortical synapses, terminal buttons, and or dendritic spines.

Activation of STPs leading to changes in gene expression is the most likely to elicit neuroplastic changes

114
Q

Neurogenesis

A

New neuronal growth
May occur in adults hippocampal and olfactory bulb regions.
Olfactory bulb neurons originate from adult neural stem cells that travel from the lateral ventricles

New hippocampal neurons are formed in the dentate gyrus of the nucleus

115
Q

Cortical Re-organization

A

Experience and stimulus can also affect the organization of the cortex of the brain.

Adults suffering tinnitus underwent a major reorganization of primary auditory cortex
Anesthetization of two fingers in adults reduced their representation in the contralateral somatosensory cortex

116
Q

Causes of neural injury

A

Brain tumors
Infections: caused by microorganisms, can result in infection
Contusions: a blow to the cranium that may penetrate the skull or not penetrate skull (closed) and damages the cerebral circulatory system, includes TBI and mTBI
Cerebrovascular events: A decreased perfusion of the brain resulting from either hemorrhage or occlusion of cerebral vessels

Most strokes are ischemic

117
Q

Ischemia induced Neural injury

A

Due to high metabolic demand of brain there is a high risk of ischemia. Limited oxygen and glucose supply. Prevents removal of metabolic waste products.
Evidence of damage is detected 1-2 days later. Damage does not occur equally (hippocampus is more susceptible)

118
Q

Ischemia Resulting in ionic imbalances

A

Deprivation of oxygen and glucose reduce energy (ATP) needed to maintain ion concentration gradients. Neuron membrane is depolarized due to change in ion concentration, voltage gated Ca ion channels open resulting in NT release.
Release is prolonged due to uncontrolled depolarization and hindered re-uptake mechanisms

119
Q

Ischemia resulting in Excitotoxicity

A

Prolonged exposure to excitatory NT (glutamate) causes activation of postsynaptic receptors at a level leading to cell death. Deterioration of cell structure and signaling capability.

120
Q

Glutamate in Ischemia-induced Cortical Damage

A

Ischemia may lead to excessive glutamate release from nearby neurons. Post-synaptic glutamate receptors are over-stimulated leading to excessive depolarization of the postsynaptic cell membrane
Na and Ca ions flood into the postsynaptic cell.
Overload of Ca can trigger activation of several signaling pathways

Free radicals, mitochondrial dysfunction, disruption of cell membrane, fragmentation of DNA

121
Q

Neuronal degeneration following an axonal transaction

A

Anterograde degeneration: degeneration of the distal portion of the axon between the cut and terminal button. Occurs rapidly (segment swells in a few hours and breaks in a few days)

Retrograde degeneration: degeneration of the proximal region between the cut and the body.

122
Q

Degenerative changes in a neuron suggest that

A

The neuron will die due to apoptosis, necrosis, or both.

123
Q

Regenerative changes in neurons suggest that

A

The cell is in the process of mass producing proteins to replace the damaged axon.
Increase in size

124
Q

Transneuronal degeration

A

Degeneration can spread to non-damaged neurons through synaptic contacts with neurons that are injured.
ANTEROGRADE - spread of degeneration from a damaged neuron to a neuron that it synapses on
RETROGRADE - reverse of anterograde

125
Q

Regeneration of axons in CNS

A

Rarely occurs

Failure to regrow often leads to permanent dysfunction

126
Q

Regeneration of PNS axons

A

Regenerate more readily than CNS (several cm)
Axons may re-establish previous synaptic contacts with peripheral targets
Re-growth an establishment of synaptic contacts may lead to functional recovery.

127
Q

Conditions for axonal regenration

A

Appropriate gene expression - injured neuron must initiate a sequence of events that leads to the activation of genetic factors that support elongation of the axon leading to a growth cone
A supportive environment

128
Q

CNS environment after an axon lesion

A

Unfavorable for re-growth. Reactive microglia, astrocytes and other cells produce inhibitory signals near the injury site that contribute to this impediment. A protein called Nogo has been found to block an axon elongation by interacting with the growth cone.
Macrophages do not promptly arrive to remove axon and myelin fragments.
Inflammatory response occurs with the release of cytokines.
CNS neurons rarely reactivate the expression of axonal regeneration-associated genes (RAG)

129
Q

CNS environment after an axon lesion

A

Severed axons undergo Wallerian degeneration
A favorable environment is created for regrowth.
Macrophages will travel to the area of damage and remove degenerating axon and myelin fragments
RAGs are often reactivated

130
Q

Neural regeneration in the PNS

A

Proximal end of a damaged nerve will begin to grow within 2-3 days.

Three events may occur
If myelin sheaths are intact the regenerating axon can grow through then to reach the original target
If the nerve is severed and the ends are seperated by a few millimeters the regrowing axon often grows into the incorrect sheath and guided to the incorrect target
If seperated by a large distance it will regrow into a mass and die

131
Q

Wallerian Degeneration and Repair

A

Degenrative process of the distal axon following axonal injury in the PNS.

1) Distal portion of the axon swells and disintegrates
2) Mononuclear leukocytes extravasated through blood vessel walls, differentiate into macrophages, accumulate near the Schwann cells and remove remaining cellular debris
4) Neuron cell body induces the activation of RAGS
5) Schwann cells secrete growth factors and proliferate
6) Schwann cells line up and act as “guidance tubes” for the new axon sprouts
7) Regenerating axon regenerates from the portion proximal to the lesion and creates sprout known as “growth cone”

132
Q

Degeneration of CNS axons

A

Different from Wallerian degeneration in the PNS. May take several months to clear fragments following injury.
Infiltration of reactive microglial cells in the area of inquiry may persist for years. Inadequate growth factors.

133
Q

Treatment for CNS injuries

A

Methods for improving QOL in those afflicted include:
Blocking inhibitory molecules
Enhancing axon regeneration
Providing tropic support to surviving neurons

It is possible to graft peripheral nerves as bridges to aid recovery and growth of CNS

134
Q

Cross-Modal plasticity

A

Without visual input to the cortex the auditory and somatosensory corticosteroids expand.
Gain an increase in the functional ability of these senses.

135
Q

Mechanisms of neural reorganization

A

Strengthening of existing connections
Establishment of new connections by collateral sprouting
Support for these mechanisms respectively comes from observations that reorganization occurs too quickly to be attributed solely to neurogenesis

136
Q

Recovery of function after brain damage

A

Most likely to occur when damage is limited and victim is young.
Difficult to discern from true recovery and compensatory changes

Improvement after brain damage has also been attributed to cognitive reserve = intelligence and education

137
Q

Treatment of NS Damage

A

Blocking Neurodegeneration - reduce neural damage (apoptosis inhibiting factors, estrogens)
Promoting Regeneration - peripheral nerve transplantation. Regeneration from myelin sheath
Neurotransplantation - transplanting fetal tissue into damaged area (substantia nigra into Parkinson’s patients); Transplanting stem cells (cells migrated to damaged area, maturation, regained motor control yet uncoordinated)
Rehabilitative training -

138
Q

Short term plasticity

A

Changes in synaptic strength that last from seconds to minutes
Allows for types of short-term memory
Manifests as an activity-dependent change in amplitude of a post-synaptic potential
May result in either facilitation or depression

139
Q

Short-term facilitation

A

Transient increase in synaptic strength
APs arrive closer together
Ca ion removal systems are overloaded
Elevated concentration of Ca ions in presynaptic terminal
Increased # of NT release following an AP
Increased amplitude of EPSPs (if successive)

140
Q

Signal Transduction Pathway and facilitation

A

Often occurs as a stepwise process in which facilitation occurs first, followed by a slow increase in efficacy known as augmentation and finally with prolonged high-frequency stimulation, a third phase of increased PSP amplitude called potentiation occurs and can last for several minutes

141
Q

Short0term depression

A

APs arrive seperated in time or low frequency stimulation
results in decreased numbers of synaptic vesicles released
Subsequent decrease in amplitude of PSPs

142
Q

Proposed mechanisms of short-term depression

A

Depletion of synaptic vesicles in the readily releasable pool
Inhibitory feedback from presynaptic autoreceptors
Ca ion channel inactivation

143
Q

Long term Potentiation

A

Best described form of plasticity. Originally demonstrated in hippocampal neurons through experiments with high frequency electrical stimulation. Neurons then demonstrated increased response to next stimulus.
Requires proximity between pre and postsynaptic neuron.

144
Q

Long term potentiation results in

A

Learning and formation of long term memory

145
Q

Structural changes in synapse with Long-term potentiation

A

Addition of AMPA receptors on the postsynaptic neuronal membrane.
Recruits “silent” synapses.
Increase in size and or density of dendritic spines
Increased arborization of dendritic trees

146
Q

Long-term plasticity

A

Changes in synapse strength that last from hours to years

147
Q

3 phases of LTP

A

Induction: Process by which high-frequency stimulation signals to the synapse to change efficacy
Expression: Actual presynaptic and/or postsynaptic changes that determine changes in synaptic efficacy
Maintenance: Mechanisms underlying the persistence of the structural changes associated with synaptic plasticity

148
Q

Activation of NMDA receptors

A

Glutamatergic receptors that are both ligand gated and voltage sensitive
Contain ion channels that move the obstructing Mg ion to allow Ca and Na ions to flow into cell.
Glutamate must be bound to receptor and there must be a depolarization (Small depolarizations may allow for passage of Na ions but not the larger Ca ions)

149
Q

AMPA receptors

A

Found on the postsynaptic membrane at excitatory gluatmatergic synapses
When bound to glutamate AMPA receptors allow Na ions into the cell thereby depolarizing the membrane

If stimulus from presynaptic neuron is high frequency then depolarization will dislodge Mg ions from NMDA receptor

150
Q

Induction of LTP

A

Following activation of NMDA receptors, Ca ions flow into the postsynaptic neuron. Influx of Ca triggers LTP in postsynaptic neuron

151
Q

Expression and maintenance of LTP

A

After Ca flux of induction
High frequency stimulation at one synapse affects changes on only that synapse while other synapses on the same postsynaptic neuron are unchanged
Protein kinases activated by ca in postsynaptic cell lead to LTP

152
Q

Structural changes with LTP

A

Additional AMPA receptors at silent synapses or synapses already containing AMPA
(Increase sensitivity to glutamate)
Increases in the size and or density of dendritic spines as well as branching of dendrites
Increased likelihood of Vesicle release from presynaptic neuron may also occur. (NO is formed in the postsynaptic neuron to diffuse back to presynaptic neuron and increase Vesicle secretion)

153
Q

Role of LTP in Learning and Memory

A

committing a piece of information to memory requires the creation of a
new neural network of synaptic connections
When an individual recalls this memory, it causes activation of the neurons of this
network to fire again

154
Q

Long-term depression

A

Synaptic efficacy is decreased by very low level stimulation or uncoordinated stimulation
Low amplitude rise in Ca in postsynaptic neuron occurs
EPSPs decrease in amplitude

155
Q

Mechanism of LTD

A

Activation of protein phosphotases (1 and 2b)
Phosphatases dephosphorylate target proteins which can result in the internalization of postsynaptic AMPA receptors through clathrin-dependent mechanisms (reduces sensitivity to glutamate)

156
Q

LTP vs. LTD

A

Both LTP and LTD require activation of NMDA receptors and entry of Ca2+ into the
postsynaptic cell
Small influxes in Ca2+ lead to depression
Large influxes lead to potentiation
LTP relies on the activities of protein kinases whereas LTD relies on protein
phosphatases
It has been proposed that the enzymes associated with LTP and LTD phosphorylate and dephosphorylate the same set of regulatory proteins