PT 536 Life and Death of Neurons

soma, dendrites, axon

What are the basic components of a neuron?

cell body

site of protein synthesis and synapatic integration

nucleus

substance on the cell body when helps make proteins via RNA transcription

nissl substance

substance on the cell body when helps make proteins via translation

synaptic integration

summation of all electrical currents within a neuron, typically arising from the dendrites

dendrites

capable of limited protein synthesis and mainly serve as the site of synaptic input

neurotransmitter receptors

surface proteins on dendrites that serve as the binding sites for chemical signals

ionotropic receptor, metabotropic receptor

after a neurotransmitter (NT) binds, the NT receptors can function as either what two things?

Ionotropic receptors

ion channels that open after the neurotransmitter binds. Small ions (Na+, K+, Ca2+, or Cl-) then move across the membrane to create electrical currents

metabotropic receptors

coupled to other proteins and kick off an intracellular signaling cascade that creates more long-lived changes in cell function

axon

incapable of protein synthesis and is the site of synaptic output

anterograde, retrograde

types of transport present in neuron axons to bring proteins where they need to go

Anterograde transport

axonal transport that brings new proteins and organelles from the soma to the axon.

retrograde transport

axonal transport that brings damaged proteins, damaged organelles, and stimulated neurotrophin receptors from the axon to the soma

True

True or False? Axons branch extensively to contact multiple target cells

Action Potentials (APs)

electrical signals created by axons that travel from the cell body throughout the axon to stimulate

neurotransmitter release

multipolar neurons

Neurons that have multiple dendrites emanating from the cell body (like the neurons in the brain)

integration of multiple synaptic inputs

purpose of multipolar neurons

bipolar neuron,

Neurons that have a single dendrite and single axon

pseudounipolar neuron

Neurons that have a single process that acts as

both dendrite and axon.

sensory

Function of neurons with a single dendrite

membrane potential (Vm)

the electrical charge a cell's membrane

-70 mV

normal Vm of a cell

makes it more positive

How does excitatory synaptic input influence Vm?

makes it negative, prevents further positivity

How does inhibitory synaptic input influence Vm?

threshold potential

The minimum membrane potential that must be reached in order for an action potential to be generated in a neuron (A)

action potential

self-propagating wave of depolarization that spreads down the axon

Na+

An early influx of ______ makes Vm positive

K+

A delayed efflux of _____ brings Vm back to a negative value.

presynaptic site

A short-lived positive Vm created by an AP stimulates neurotransmitter release from what location?

synaptic vesicles

Neurotransmitters are held within the neuron in what structures?

Ca2+

What ion enters into the neuron in response to a positive Vm in order to facilitate NT release from the presynaptic site?

synaptic vesicles fuse with membrane

How do NTs leave the presynaptic site?

synaptic cleft

The narrow gap that separates the presynaptic neuron from the postsynaptic cell.

postsynaptic site

The cell that is receiving the signal, contains protein receptors

glutamate, GABA

Nearly all neurons in the central nervous system release either what two NTs?

GABA

between glutamate and GABA, which one is inhibitory?

ACh, serotonin, dopamine, NE, epi

Neuromodulatory transmitters that generally create slower, more long-lived changes

in Vm

ACh, NE

Neurons in the peripheral nervous system release either what two neurons?

neuropeptides

Brain chemicals, such as enkephalins and endorphins, that regulate the activity of neurons

corticospinal tract

A simple neural pathway that illustrates the alternating pattern of electrical and chemical signaling, which is responsible for conscious movement

UMNs

motor neurons in the cerebral cortex that project their axon down the ventral horn of the spinal cord in order to control the activity of lower motor neurons (LMNs)

chemical

In the corticospinal tract, UMNs receive synaptic input from other cortical regions and the thalamus. Is this a chemical or electrical signal?

electrical

UMN dendrites receive signals and create currents generated in the dendrites and summed in the cell body, then sent down the axon. Is this electrical or chemical?

myelin

a lipid- and protein-rich that insulates axons

internodes

myelinated regions of the axon

nodes

unmyelinated regions

cost, space, speed

3 advantages of myelination

saltatory conduction

Rapid transmission of a nerve impulse along an axon, resulting from the action potential jumping from one node of Ranvier to another, skipping the myelin-sheathed regions of membrane.

free radicals

Active transport requires ATP, and ATP synthesis creates ____________________, which can damage lipids, proteins, and DNA.

Oligodendrocytes

synthesizes myelin in the CNS

save space

Goal of the myelin in the CNS created by oligodendrocytes

Schwann cells

synthesizes myelin in the PNS

mechanical protection

Goal of the myelin in the PNS created by Schwann cells

Ependymal cells

produce cerebrospinal fluid (CSF) and form the blood-CSF barrier.

endfoot processes

physical barrier created by astrocytes

glial limitans

collection of endfoot processes that surrounds the brain to restrict diffusion into and out of the brain.

vascular epithelial cells

Endfoot processes interact with these cells to regulate blood flow

and help maintain the blood-brain barrier.

Perisynaptic processes

provide the glial component at synapses

perinodal processes

contact the nodes on axons, likely to help buffer K+ that exits the axon.3

regulate K+, recycle GABA + glutamate, shuttle metabolic substrates

3 main functions of astrocytes

microglia

macrophages that enter the nervous system throughout development

gliosis

During injury, astrocytes and microglia alter their morphology and divide in what process?

gliosis

proliferation of astrocytes/microglia in an area of neuron degeneration leading to a glial scar.

glial scar

consists of modified extracellular matrix proteins that create a rubbery, tenacious, growth-blocking membrane

amoeboid

Microglia respond to injury by withdrawing their processes to adopt what form?

reactive microglia

migrate to the site of injury and act as macrophages

Necrosis

the rupturing of the cell membrane or plasmalemma

by moving ions across plasmalemma

how are electrical currents created?

ion channels

A transmembrane protein channel that allows a specific ion to diffuse across the membrane down its concentration or electrochemical gradient.; have the fastest rate of influx.

carriers/transporters

move solutes across the membrane through a series of conformational changes. This reliance on shape changing dramatically slows the rate of ion movement, but they can move solutes against their concentration gradient

ion pumps

undergo conformational changes, are slow (up to 103 ions per second), and move solutes against their concentration gradient using ATP hydrolysis

Na+, Cl-

what ions are high in extracellular fluid?

K+

what ions are high in intracellular fluid?

passive

Opening and closing of ion channels creates an electrical current through passive or active transport of ions

pumps

How do neurons maintain an ionic imbalance?

aquaporins

water channel proteins through which water moves passively into and out of neurons

osmosis

Diffusion of water through a selectively permeable membrane

traumatic injury, inflammation, hyperactivity

common causes of necrosis

osmotic necrosis/oncosis

With hyperactivity in neurons, ion currents cause the movement of water, causing these neurons to take on water and swell until the plasma

OMM

Part of the mitochondria that contains calcium channels that allow mitochondria to buffer calcium levels within the cell

IMM

Part of the mitochondria that contains the electron transport chain and ATP synthase, working together to generate ATP in aerobic respiration

Hydrogen gradient

Gradient formed by the difference in proton concentration across the mitochondrial membrane; form of potential energy that provides energy to form ATP (within the intermembrane space)

free radicals/superoxide

Produced from the mitochondria as a byproduct of ATP production

cell thinks it should die

If the ETC is impaired, what happens to the cell?

cytochrome c

soluble ETC protein, that when in the cytoplasm, may indicate the ETC is impaired

IMM

normal location of cytochrome c when mitochondria has a functioning ETC

apoptosis

what kind of cell death does cytochrome c trigger?

apoptosis

sequential, orderly cleavage of intracellular components

apoptosome

When cytochrome c enters the cytoplasm of a cell it binds with a protein called Apaf-1 to form what?

apoptosome

collection of proteins that triggers apoptosis

caspases

apoptosomes activate what kind of proteins?

caspases

collection of proteins that

cut up specific cellular components

pro-caspases

inactive caspases contained in all cells and kept inactive by a regulatory domain

cutting off regulatory domain

how are procaspases activate?

initiator caspases

first caspases to be activated, cutting up other pro-caspases to turn them on

effector caspases

turned on by initiator caspases, and cut up cellular components in order to carry out apoptosis

Bcl-2 proteins

many different proteins that regulate the permeability of the OMM within a cell

Pro-apoptotic Bcl-2 proteins

create pores in the OMM to stimulate apoptosis

Anti-apoptotic Bcl-2 proteins

bind to pro-apoptotic Bcl-2 proteins and prevent them from killing the cell.