Lecture 4 Neurons Cellular and Network Properties

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Neurons

Cellular and Network


Properties

AMER H. RAHHAL, MD, PhD


Neurons: Cellular and Network Properties
Basic Functions
➢Sensory input: sensory or afferent neuron
detect internal or external changes (stimuli)
and send the message to the brain or spinal
cord.

➢Integration: interneurons in the brain or


spinal cord process and interpret the message
from the sensory neurons and relay the
massage back to body parts.

➢Motor output: motor or efferent neurons


receive the message from interneuron and
produce a response at the effector organ (a
muscle or a gland).
Neurons: Cellular and Network Properties
Basic Functions

➢Sensory Input ➔ Monitor changes inside and outside the body.

➢Integration ➔ Processes information and makes decisions.

➢Motor Output ➔ Response by activating glands or muscles.


Neurons: Cellular and Network Properties
Organization of Nervous System

Central Nervous System (CNS)

➢ Parts: Brain and spinal cord.


➢ Functions:
I. Body’s control system.
II. Receives sensory input.
III. Relays motor impulse via
efferent nerves.
IV. Center for higher function as
intelligence, memory, emotion.
Neurons: Cellular and Network Properties
Organization of Nervous System

Peripheral Nervous System (PNS)

➢ Parts: Nerves outside the CNS.


➢ Function:
I. Sensory nerves to CNS (afferent).
Carries impulses from receptors to
CNS.
II. Motor (efferent) nerves from CNS to
effector. Carries impulses from CNS
to effector (muscles or glands).
Neurons: Cellular and Network Properties
Organization of Nervous System

Peripheral Nervous System (PNS)

➢ Divisions of the motor system


I. Somatic Nervous System.
✓ Voluntary afferent nerves from skin and
muscles go to CNS. Efferent nerves from
CNS to skeletal muscles.
II. Autonomic Nervous System.
✓ Involuntary afferent nerves are from
internal organs to CNS. Efferent nerves
from CNS to cardiac or smooth muscles.
Neurons: Cellular and Network Properties
Organization of Nervous System

Autonomic Organization

➢Sympathetic
➢“Fight or Flight”

➢Parasympathetic
➢“Rest or Digest”
Neurons: Cellular and Network Properties
Organization of Nervous System
Neurons: Cellular and Network Properties
Organization of Nervous System
Neurons: Cellular and Network Properties
Cells of the Nervous System

➢Made of two different varieties of cells:

➢Neurons: nerve cells that are specialized to


detect and react to stimuli, by generating
and conducting nerve impulses.

➢Neuroglial cells: accessory cells for filling


spaces and supporting neurons.
Neurons: Cellular and Network Properties
Cells of the Nervous System

➢Microscopic anatomy of neurons:


➢ All neurons have a cell body called Soma which contains a
nucleus, organelles, and a modified endoplasmic reticulum
called Nissl body.
Neurons: Cellular and Network Properties
Cells of the Nervous System

Neuron
Neurons: Cellular and Network Properties
Cells of the Nervous System

➢Structural unit of nervous system

➢Conduct messages in the form of nerve


impulses from one part of the body to
another
Neurons: Cellular and Network Properties
Cells of the Nervous System

Parts of Neuron
A. Cell body: consists of a nucleus with easily visible nucleolus
and some special organelles.

1. Nissl bodies: (rough ER)

2. Neurofibrils: which are intermediate filaments to maintain


cell structure and integrity

3. Golgi Apparatus: extra important in neuron


Neurons: Cellular and Network Properties
Cells of the Nervous System

B. Processes

1. Dendrites: receive information for neuron that may or may


not become an Action Potential.

2. Axons:
✓ one per neuron

✓ Arises from cell body at the axon hillock

✓ Sends info away from neuron

✓ Transmits action potentials


Neurons: Cellular and Network Properties
Structural Classification of Neurons

➢ Multipolar neurons
✓ Many extensions from the cell body.
✓ It is located mostly in CNS.
✓ It is most motor neurons.
Neurons: Cellular and Network Properties
Structural Classification of Neurons

➢ Bipolar neuron
✓ Has two processes, one axon and one dendrite.
✓ Its functions is that dendrite specialized to receive a specific stimulus.
✓ The axon conducts action potential to the CNS.
✓ It is located in the retina of the eye, nasal cavity.
Neurons: Cellular and Network Properties
Structural Classification of Neurons

➢ Unipolar neuron
✓ Has a single process extending form the cells body,
✓ One branch extends to the CNS, while one branch
extends to the periphery and that has a dendrite.
Neurons: Cellular and Network Properties
Structural Classification of Neurons

➢ The anaxonic neuron


✓ Can transport things back and forth.
✓ They are found in the brain and can sense organs.
✓ It is small and a cell process look alike.
Neurons: Cellular and Network Properties
Functional Classification of Neurons

❖Sensory Neurons
➢Afferent neurons of PNS
✓ Monitor internal environment (visceral sensory neurons).
✓ Monitor effects of external environment (somatic sensory neurons).
➢Types of Sensory Receptors
❑Interoceptors
✓ Monitor internal systems (digestive, respiratory, cardiovascular, urinary,
reproductive).
✓ Internal senses (taste, deep pressure, pain).
❑Exteroceptors
✓ External senses (touch, temperature, pressure).
✓ Distance senses (sight, smell, hearing).
❑Proprioceptors
✓ Monitor position and movement (skeletal muscles and joints).
Neurons: Cellular and Network Properties
Functional Classification of Neurons

❖Motor Neurons
➢Efferent neurons of PNS
✓ Carry instructions from CNS to peripheral effectors.

✓ Via Efferent Fibers (axons).

➢Two Major efferent systems


❑ Somatic nervous system
✓ Includes all somatic motor neurons that innervate skeletal muscles.

❑ Autonomic (visceral) nervous system (ANS)


✓ Visceral motor neurons innervate all other peripheral effectors.

✓ Smooth muscle, cardiac muscle, glands, adipose tissue.


Neurons: Cellular and Network Properties
Functional Classification of Neurons

❖Interneurons
➢Association neurons
➢Most are located in brain, spinal cord.
✓ Between sensory and motor neurons

➢Are responsible for:


✓ Distribution of sensory activity
✓ Coordination of motor activity

➢Are involved in higher functions


✓ Memory, planning, learning
Neurons: Cellular and Network Properties
Axons Transport

➢ Slow axonal transport


Moves material by axoplasmic
flow at rate 0.2–2.5 mm/day.
➢ Fast axonal transport
Moves organelles at rates of up
to 400 mm/day.
✓ Forward transport: from cell
body to axon terminal
✓ Backward transport: from
axon terminal to cell body
Neurons: Cellular and Network Properties
Glial Cells and Their Functions GLIAL CELLS

are found in

Peripheral nervous system

contains

➢Glial cells provide physical


and biochemical support Satellite
cells
Schwann cells

for neurons. forms

Myelin sheaths

secrete

Support Neurotrophic
cell bodies factors

Glial cells and their functions


Neurons: Cellular and Network Properties
Glial Cells and Their Functions
GLIAL CELLS

are found in

➢ Glial cells maintain an Central nervous system

contains
environment suitable
for proper neuron
function
Oligodendrocytes Microglia (modified Ependymal
immune cells) Astrocytes
cells

forms act as

Myelin sheaths Scavengers

provide help form secrete take up create

Blood- Source of Barriers


Substrates for brain Neurotrophic K+, water, neural between
ATP production barrier factors neurotransmitters stem cells compartments
Electrical Signals
Ionic Concentrations and Potentials

➢At disequilibrium, cells and solution are electrically


and chemically imbalance.

➢ Active transport carrier protein is inserted into the


membrane

➢Energy is need to pump one cation out of the cell


➔ net charge of -1 in the cell and +1 outside the
cell.

➢The input of energy to transport ions across the


membrane has created an electrical gradient.
Electrical Signals
Ionic Concentrations and Potentials

➢At equilibrium state, cells and solution are electrically and


chemically equal.
Electrical Signals
Ionic Concentrations and Potentials

➢On absolute charge scale, ECF


would be at +1 and ICF at -1.

➢On relative scale, ECF is assigned


a value of zero ➔ left shift ➔ the
charge will be -2 inside the cell.
Electrical Signals
Ionic Concentrations and Potentials
➢ Sidedness means that the electrical charges on one side of the membrane
(positive or negative) are different than on the other side.

➢ Why does sidedness exist?

✓ Different permeability

✓ Pumps & Protein channels

✓ Most important reason: potassium leak channels. Potassium leaves by leak


channels, contributing to negativity.

➢ How does a membrane become sided?

✓ Primary and secondary active transport, or pores that allow only one
particular solute to move. These things make a higher concentration on one
side. Therefore, sidedness is caused by proteins.
Electrical Signals
Ionic Concentrations and Potentials

An electrical gradient
between ECF and ICF
is known as the
Resting Membrane
Potential difference.
Electrical Signals
Ionic Concentrations and Potentials

➢ The Resting Membrane Potential Is Due Mostly to Potassium.


➢ The equilibrium potential for any ion at 37° C (human body temperature) can be
calculated using the Nernst equation:

Where 61 is 2.303 RT/F at 37° C*


z is the electrical charge on the ion ( 1 for K )
[ion]out and [ion]in are the ion concentrations outside and inside the cell. Eion is
measured in mV.
Electrical Signals
Ionic Concentrations and Potentials
Electrical Signals
Ionic Concentrations and Potentials
Electrical Signals
Ionic Concentrations and Potentials

➢ Concentration gradient for K


is 150mM inside and 5mM outside
the cell
➢ The equilibrium potential for
potassium (EK) is -90 mV
Electrical Signals
Ionic Concentrations and Potentials

➢ The concentration gradient


moving Na+ into the cell (150
mM outside, 15 mM inside) is
exactly opposed by a
positive membrane potential
of 60 mV
Electrical Signals
Ionic Concentrations and Potentials
➢ If a cell is permeable to several ions, we cannot use the Nernst equation to
calculate membrane potential. Instead we must use a related equation

called the Goldman equation


➢ In fact, living cells are not permeable to only one ion

Goldman Equation

Pk[Ko] + PNa[Nao]
Vm = 60 log10
Pk[Kin] + PNa[Nain]

= -70 mV
Electrical Signals
Ionic Concentrations and Potentials

➢ Cell has a resting membrane potential of -70 mV.


➢ Most cells are about 40 times more permeable to
K than to Na.
➢ As a result, a cell resting membrane potential is
closer to the EK of -90 mV than to the ENa of +60
mV.
➢ Na+ and K+ that leaks is promptly pumped back
by the Na – K ATPase → helps maintain the
electrical gradient.
Electrical Signals
Membrane Potentials
➢ The extracellular electrode is set at 0 mV,
and the intracellular electrode records the
membrane potential difference.
➢ The membrane potential (Vm) begins at a
steady resting value of -70 mV
➢ When the trace moves upward (becomes
less negative) the cell is said to have
depolarized.
➢ A return to the resting membrane potential is
termed repolarization.
➢ If the resting potential (becomes more
negative) the potential difference has
increased, and the cell has hyperpolarized.
Electrical Signals
Action Potential

➢ An action potential is a rapid sequence of changes in the voltage across a membrane.

➢ It is a short – lasting event in which the electrical membrane potential of a cell rapidly
rises and falls, following a consistent trajectory.

➢ Action potentials occur in several types of animal cells, called excitable cells, which
include (neurons, muscle cells, and endocrine cells).

➢ Action potentials are generated by special types of voltage-gated ion


channels embedded in a cell's plasma membrane.

➢ These channels are shut when the membrane potential is near the resting potential of the
cell, but they rapidly begin to open if the membrane potential increases to a precisely
defined threshold.
Electrical Signals
Action Potential

➢ The action potential has five


steps:
1. Reaching threshold.
2. Depolarization.
3. Repolarization.
4. Hyperpolarization.
5. Return to resting potential.
Electrical Signals
Action Potential

➢ Threshold: a certain minimum strength


required to stimulate an axon in order
to generate action potential.
➢ All or none: each action potential has
the same amplitude independently
from the strength of the stimulus.
➢ Refractory period: a second action
potential cannot occur during this
period.
HOW ACTION POTENTIAL HAPPENS?
Electrical Signals
Action Potential

Cell is more positive outside than inside.


Electrical Signals
Action Potential

As ions move across the membrane the potential


increases.
Electrical Signals
Action Potential

Graded potentials have


brought the membrane
potential up to threshold.

✓ Level of depolarization needed to trigger an action potential (most neurons have a threshold at -50 mV)
✓ Threshold reflects the need to trigger the opening of the voltage-gated sodium channel (need a depolarization
of about 10 to 15 mV to open)
Electrical Signals
Action Potential

Action potential rising phase


✓ As sodium channels open, Na+ ions flow into cell, depolarizes the cell more and more sodium channels
open = drives the membrane potential towards a peak of the Nernst equilibrium potential for Na+
Electrical Signals
Action Potential

✓ During an action potential the membrane potential goes towards the Nernst equilibrium potential for Na+.
✓ In terms of Goldman-Katz equation now permeability to Na+ is dominant (K+ and Cl- minor components)
therefore membrane potential goes towards ENa.
Electrical Signals
Action Potential

K+ moves out of the cell along its gradient and the


inside of the cell becomes more and more negative.
Electrical Signals
Action Potential

Falling Phase of Action Potential


➢ After reaches peak now action potential falls,
membrane potential falls back towards rest.
➢ Why doesn't the action potential stay around
ENa?
Two reasons:
I. Na+ channels move into an inactive state (close)
II. Delayed K+ channels open
Electrical Signals
Action Potential

➢ Inactivating Na+ channels.


✓ Na+ channels go to an inactivated state after
1-2 msec. after first opening.
✓ Inactivated ➔ can NOT be reopened.
✓ Therefore the membrane potential now
determined mostly by K+ (same as for resting
potential) and membrane starts to repolarize.
Electrical Signals
Action Potential

➢ Delayed K+ channels open (called delayed rectifier;


voltage-gated like Na+ channel)
✓ Open after about 1-2 msec. of threshold depolarization.
Now K+ flows out of the cell and speeds the
repolarization process.
✓ Cause the hyperpolarization after the action potential
because open K+ channels make the K+ permeability
higher than at rest and membrane more negative on
inside.
✓ Hyperpolarization of membrane causes K+ channels to
close.
✓ Membrane settles back to rest.
Electrical Signals
Action Potential

Hyperpolarization occurs when the membrane potential drops below


resting potential; caused by the continuing movement of K+ out of the
cell.
Electrical Signals
Action Potential

➢ Voltage-gated Na+ channels and voltage-gated K+ channels now closed so the membrane goes back to
the resting state i.e. the leak channels are the only channels open and again set the membrane potential.
Electrical Signals
Action Potential

Returns to its original state where the outside is more positive than the
inside and the membrane potential is -70 mv.
Electrical Signals
Action Potential

➢ A second action potential cannot be triggered for about 2 msec, no matter how
large the stimulus. This 2 msec represents the time required for the Na+ channel
gates to reset to their resting positions and is called the absolute refractory period
➢ Relative refractory period follows the absolute refractory period. During the relative
refractory period, some but not all Na+ channel gates have reset to their original
positions. Those channels can be opened by a higher-than-normal graded
potential
➢ This means that a stronger-than-normal depolarizing graded potential is needed to
bring the cell up to threshold
➢ During the relative refractory period, K+ channels are still open
Electrical Signals
Ion Movement During an Action Potential
Neurons: Cellular and Network Properties
Action Potentials

Action potentials are very brief, large


depolarizations that travel for long
distances through a neuron without
losing strength. Their function is rapid
signalling over long distances.
Neurons: Cellular and Network Properties
Graded Potentials

➢ Graded Potentials reflect stimulus strength.

➢ The wave of depolarization that moves


through the cell is known as local current
flow.
Neurons: Cellular and Network Properties
Graded Potentials

➢ The cell body receives stimulus.

➢ The strength is determined by how much


charge enters the cell.

➢ The strength of the graded potential


diminishes over distance due to current leak
and cytoplasmic resistance.

➢ The amplitude increases as more sodium


enters, the higher the amplitude, the further
the spread of the signal.
Neurons: Cellular and Network Properties
Graded Potentials

➢Subthreshold and suprathreshold


graded potentials in a neuron.

➢If a graded potential does not go


beyond the threshold at the
trigger zone an action potential
will not be generated.
Neurons: Cellular and Network Properties
Graded Potentials

➢ Why do graded potentials lose strength as they move through the cytoplasm?

✓ There are two reasons:

I. Current leak: Some of the positive ions leak back across the membrane
as the depolarization wave moves through the cell. The membrane in
the neuron cell body is not a good insulator and has open leak channels
that allow positive charge to flow out into the ECF.
II. Cytoplasmic resistance: The cytoplasm itself provides resistance to the
flow of electricity, just as water creates resistance that diminishes the
waves from the stone.
Neurons: Cellular and Network Properties
Graded Potentials

➢ Depolarizing grading potential


are excitatory.
➢ Hyperpolarizing graded potentials
are inhibitory.
➢ Graded potential:
➢ Short distance.
➢ Lose strength as they travel.
➢ Can initiate an action potential.
Neurons: Cellular and Network Properties
Electrical Signals: Trigger Zone

➢ Graded potential enters trigger zone, summation brings it to a level above threshold.

➢ Voltage-gated Na+ channels open and Na+ enters axon, a segment of the membrane
depolarizes.

➢ Positive charge spreads along adjacent sections of axon by local current flow, as the signal
moves away the currently stimulated area returns to its resting potential.

➢ Local current flow causes new section of the membrane to depolarize, this new section is
creating a new set of action potentials that will trigger the next area to be depolarized.

➢ The refractory period prevents backward conduction; loss of K+ repolarizes the membrane,
Once the Na+ close they will not open in response to backward conduction until they have
reset to their resting position- ensures only one action potential is initiated at time.
Neurons: Cellular and Network Properties
Graded Potential vs Action Potential
Neurons: Cellular and Network Properties
Frequency of Action Potentials

➢ The frequency of action potential firing


indicates the strength of a stimulus.
✓ "Wave" of Aps.
✓ Proportional Neurotransmitter (NT)
Release.
✓ Stronger GP Initiates more APs & more
NT.
➢ A GP reaching the trigger zone does not
usually trigger a single AP.
➢ Instead, even a small GP that is above
threshold triggers a burst of AP.
Neurons: Cellular and Network Properties
Frequency of Action Potentials

The amount of neurotransmitter released at the axon terminal is directly related


to the total number of action potentials that arrive at the terminal per unit time.
Neurons: Cellular and Network Properties
Frequency of Action Potentials

Stronger stimuli release more neurotransmitter into the synapse.


Neurons: Cellular and Network Properties
Conduction of Action Potentials

➢ The wave of depolarization that moves


through the cell is known as local current
flow.
➢ The net movement of positive electrical
charge.
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Conduction of Action Potentials

➢ Because of the absolute refractory period, a second action potential


cannot occur before the first has finished.
➢ Action potentials moving from trigger zone to axon terminal cannot
overlap and cannot travel backward.
Neurons: Cellular and Network Properties
Conduction of Action Potentials

➢ Depolarization makes a neuron more likely to fire an action


potential, depolarizing graded potentials are considered to be
Excitatory. (involve Na channel)
➢ Hyperpolarizing graded potential moves the membrane potential
farther from the threshold value and makes the neuron less likely to
fire an action potential. hyperpolarizing graded potentials are
considered to be Inhibitory. (involve Cl channel)
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Conduction of Action Potentials
Neurons: Cellular and Network Properties
Speed of Conduction

➢Larger Diameter Faster Conduction

➢Myelinated Axon Faster Conduction


✓Salutatory Conduction

✓Disease Damage to Myelin

➢Chemicals that Block Channels

➢Alteration of ECF Ion Concentrations


Neurons: Cellular and Network Properties
Speed of Conduction

➢ Larger Diameter Neurons Conduct


Action Potentials Faster.
Neurons: Cellular and Network Properties
Speed of Conduction

➢ In myelinated neurons the cell


membrane of the Schwann cell
wraps around the axon many
times (myelin sheet).
➢ Conduction Is Faster in Myelinated
Axons.
Neurons: Cellular and Network Properties
Saltation

➢ No depolarisation occurs under the myelin.


➢ Depolarisation only happens at the nodes.
➢ All the Na+ channels are concentrated at the nodes.
Neurons: Cellular and Network Properties
Saltation
Neurons: Cellular and Network Properties
Alteration of ECF Ion Concentrations

➢ When blood K is in the normal range, a


subthreshold graded potential does not
fire an action potential.
Neurons: Cellular and Network Properties
Alteration of ECF Ion Concentrations

➢ When blood K is in the normal range,


a suprathreshold stimulus will fire an
action potential.
Neurons: Cellular and Network Properties
Alteration of ECF Ion Concentrations

➢ When blood K is increased


Hyperkalemia, brings the membrane
to the threshold. Now a stimulus that
would normally be subthreshold can
trigger an action potential.
Neurons: Cellular and Network Properties
Alteration of ECF Ion Concentrations

➢ When blood K is decreased


Hypokalemia, hyperpolarizes the
membrane and makes the neuron less
likely to fire an action potential in
response to a stimulus that would
normally be above the threshold.

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