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4PY019

Human
Nervous System

Dr Bartholomew Harvey
University of Wolverhampton
November 2024
Before we start….

You Said: We’ve done:

There is too much lecturing in the In this lecture, there will be 2


scientific courses, we want more opportunities for independent/group
workshops/group work work.

Work in Progress for all of us.


Human Nervous System
Central Nervous
System (CNS)
Brain
Peripheral Nervous System
Spinal Cord (PNS)
• Peripheral Nerves
• Cranial Nerves (12 pairs)
Process sensory input
• Spinal Nerves (31 pairs)
Generates motor output
❖ Afferent sensory communication with CNS
❖ Efferent motor output from CNS

Afferent nerves take signals from peripheral tissues and external


environment to the central nervous system (CNS).

Efferent nerves take signals from the CNS to peripheral tissues.


Trick to remember this when thinking about the CNS
afferent arrives
efferent exits.
Neurons
Cells that form part of the central and peripheral nervous system carry signals
along their membranes in the form of nerve impulses or action potentials
• High energy need – Constant O2 and
Glucose required

• Amitotic - cannot divide once formed.

• Extreme longevity compared to other cells.

Structure

• A receptive (input) region - Dendrites

• A cell body - Soma

• A conducting component - Axon

• A secretory (output) region - Telodendria,


synaptic terminals
Action Potentials Change in Vm during AP

AP = Action Potential

Vm = Voltage Membrane

1 – Resting potential
2 – Depolarisation
3 – Repolarisation
4 – Hyperpolarise
Neurons – Microscopic view
Dendrite of Neurons
Dendrites receive signal inputs, which then
get converted into changes of membrane
voltage (Vm).
These electrical signals are not action potentials, but are
short distance graded potentials, which then spread.

Integration of Vm changes by different


dendrites results in an average Vm change
reaching the soma.

Eye – Optic Nerve Ear – Hearing Nerve Synapses


Stimuli - Light Stimuli - Sound Neurotransmitters
SOMA – Cell Body of Neurons
- This consists of a large nucleus with a noticeable
nucleolus surrounded by granular cytoplasm (owl’s
eye).
Nucleus
- Mitochondria, Golgi are found throughout the cell
body.

- Microtubules and neuro-filaments are also seen


throughout and are important in intracellular
transport and in maintaining cell shape.
Axon
Function of the Cell Body
- The cell body aggregates all the inputs from
Nucleolus the dendritic tree.
Axon Hillock
- Then changes in Vm get transferred to the
axon hillock.
Axon Hillock
- This is the first part of
the output pathway of
the neuron.

Function of the Axon hillock


- It generates action potentials if receiving enough stimulation from the
cell body.

- It expresses the ion channels that are needed for action potentials
Axon of Neurons
- Each neuron has a single axon arising from the axon hillock

- Different axons can vary in their diameter, which will reflect in their conduction speeds
- Small diameter axons have a high resistance, therefore slower conduction speeds

- Large diameter axons have a low resistance, therefore faster conduction speeds

- Individual axons retain a uniform diameter along their length

- Axons may occasionally have branches coming off, called axon collaterals

Functions of the axon


- Axons allow for action potential propagation towards targets.

- Axons also allow for (axoplasmic) transport of molecules to the nerve terminals.
Myelin and Axons
Myelin Sheath is formed by myelinating cells (Schwann cells or oligodendrocytes),
wrap themselves around an axon in a Swiss roll fashion.

Initially this is quite loose, but over time cytoplasm is squeezed out to form many
layers of tightly coiled membrane.

The nucleus and cytoplasm is found underneath the outermost part of the plasma
membrane

The resulting cytoplasmic-free membrane has very few proteins and very few ion
channels or transporter molecules that makes it a very good electrical insulator.
Myelin and Axons cont…
Myelinated nerve fibres conduct action potentials rapidly when compared to
unmyelinated axons (NOTE: dendrites are always unmyelinated).

Gaps between myelin sheath called “Node of Ranvier” cause action potentials to
jump from node to node, which greatly increases conduction speeds for a given
axon diameter. This is known as saltatory conduction (Italian: saltare = jump).
Synapse
Ca2+ V.O.C. Presynaptic
Ca2+ action
nerve
neuro- vesicle potential
neuron
transmitter

terminal
synaptic cleft
vesicle
fusion
postsynaptic
membran
e
agonist
receptor
receptor
binding
receptor
activation

Postsynaptic membrane response


Switching off a synapse
Action potential propagation and neurotransmitter release ceases.

Neurotransmitter is removed from the synaptic cleft by either:

Neurotransmitter breakdown Neurotransmitter reuptake


Synapses vs NMJ
Synapse is a general term
A junction between a neuron and another cell
e.g. a neuron connecting to another neuron

NMJ (Neuromuscular Junction) is a type synapse


I.e. junction between a neuron and another cell
(Muscle fibres)
It can only be a NMJ if the neuron connects to a muscle fibre
it is not a general term
Types of Neurons
https://youtu.be/X4uuCgElLK8

Functional classification Morphological classification


o Sensory (afferent) neurons o Pseudo-unipolar neurons (only
o Motor (efferent) neurons axons, no dendrities) (sensory neurons)
o Interneurons (connect sensory to motor
neurons)

o Bipolar neurons (1 axon, 1 dendrite)


(olfactory epithelium, retina)
sensory neuron

interneuron
o Multipolar neurons (Many dendrites, 1
axon) (motor neurons)

Unipolar neurons
(only invertebrates, not in human)

motor neuron
Round 1 – Neuronal Conditions

MA007 MA003/4
Ion Movement & Energy
Cells use membrane transport pathways
• ‘passive’ transport – a “downhill process”. No energy required as there is an
electrochemical gradient
• ‘active’ transport – an ‘uphill’ process, so requires energy, normally from ATP. It is against
the gradient.
• secondary active transport – combines both uphill & downhill processes
• endocytosis, exocytosis – specialised for large molecules such as proteins

Linked to the Cells and Solute lecture at the start of the year
Action Potentials
Change in Vm during AP

1 – Resting potential;
2 – Depolarisation
3 – Repolarisation
4 – Hyperpolarise

• Moving charges ions (positive and


negative) changes Vm
• This is done via membrane
transport pathways
Basic Ion Channel Properties
Basic Properties
• Biological tool (proteins)
• Selective (usually through a filter)
• Stimuli varies (Ligand, voltage, mechanical)
• Modulated (phosphorylation, or lack there of)
• When open, the ion movement is passive

Na+ K+ Ca++
4mM
145mM 2.5mM

OUT

IN Na+ K+ Ca++
20mM
150mM 0.0001mM
Electro
Chemical
No electrochemical gradient, no movement
Ohm’s Law
Channels closed
Very high resistance (R)

K+

Channels Open
Lower resistance (R)
Na+ Ca++

we can make measurements of this – electrophysiology, important technique in research


Resting Membrane Potential (RMP)

RMPs are typically negative, around -40 to -70mv depending on the cell type
• this means there is a negative gradient from inside to out (Na+/K+ pump)
• an electrical gradient, as well as any concentration gradients
• if channels in the membrane opened, ions could move down the electrical gradient
• if that gradient is big enough they might do this against a concentration gradient
• gradient a combination of both – ‘electrochemical’
• ions will tend to ‘flow’ to an equilibrium, which can be calculated.
Nernst Equation
Gas constant Temperature (In Kelvin)
8.135 J K-1 mol-1 Kelvin = 273 + Celsius.

RxT [ion]out
Erev = x ln
zxF [ion]in

Valency Faraday’s Constant


Total charge of the ion
96500 C mol-1

*58 if room temp


[ion]out
EmV = 61.5* x log10 Invert for negative charge
[ion]in
(e.g. Cl-)
Active Transport and RMP
The Na+ / K+ transporter (‘pump’) is one key membrane protein – ‘active’ transport
• requires energy from ATP (large amount of resting metabolism goes into servicing this)
• shifts 3 Na+ out and 2 K+ into the cell against their concentration gradient each cycle
• sets a new gradient (in fact stores energy from ATP hydrolysis as an ion gradient)
• is electrogenic in function – ion movements are a flow of current
VO Na+
VO K+ channels
Sensory cell channels
open
[Na+ 150 mM] outside close

[K+ 15 mM] outside


VO Na+
1 Na+
channels
Na+ open
VO K+
- channels close
+
-
+ -+
- 4
Na+ + K+ K+ K+
-
+
Na+
-
+ +-
+
+-
+
+-
+
+-
+
+-
+ 5
2
+ - -
+- +-
- -
+- +-
- +-
-
[Na+ 15 mM] inside Na+ Na+ Na+
3 6
[K+ 150 mM] inside

Axon
Soma direction of propagation
Other Cells of the CNS
Glia
Cells that form part of the central and peripheral nervous system. Glia means “Glue”
- Have a supporting role (help maintain the environment around the neurons)
- Have an important role in myelinating neurons

Glia cells in the Central Nervous System CNS


Oligodendrocytes Astrocytes Microglia Ependymal cells
Myelinate neurons in Supporting neurons environment Phagocytose foreign Produce CSF in
the CNS Involved in BBB organism cerebral ventricles
Other Cells of the PNS
Glia cells in the Peripheral Nervous System PNS

Schwann Cells Satellite Glial Cells


Myelinate axon of PNS Myelinate the cell body of PNS
neurons neurons

https://brainstuff.org/blog/what-are-satellite-glial-
https://www.ncbi.nlm.nih.gov/books/NBK544316/figure/article-28765.image.f1/
cells
Round 2 – Channel Blockers
MA003/4
MA007
Me
Drug Name Type of Drug/Condition it treats The channels it blocks
(and where it is located)

Verapamil Hypertension and/or Angina Calcium Channel Blocker


(Heart)

Amiloride Hypertension, Heart Failure and Sodium Channel Blocker


Hypokalemia????? (Kidney/Heart)

Oxcarbazepine Anticonvulsant, usually used to Voltage-gated Sodium Channel


????? treat focal seizures Blocker (Brain)

Cheat Screen
Lidocaine Local anaesthetic Voltage-gated sodium channels
?????
(Nervous System)

Nifedipine Treats Rynaud’s Syndrome Calcium Channel Blockers


?????

Quinidine Antiarrhythmic Sodium, Potassium and some


????? ?????blocked.
Calcium Channels
Drug Name Type of Drug/Condition it treats The channels it blocks
(and where it is located)

Verapamil Hypertension and/or Angina Calcium Channel Blocker


(Heart)

Amiloride Hypertension, Heart Failure and Sodium Channel Blocker


Hypokalemia (Kidney/Heart)

Oxcarbazepine Anticonvulsant, usually used to Voltage-gated Sodium Channel


treat focal seizures Blocker (Brain)

Lidocaine Local anaesthetic Voltage-gated sodium channels


(Nervous System)

Nifedipine Treats Rynaud’s Syndrome Calcium Channel Blockers

Quinidine Antiarrhythmic Sodium, Potassium and some


Calcium Channels blocked.
https://www.frontiersin.org/journals/pharma
cology/articles/10.3389/fphar.2010.00137/f
ull
Anatomy of CNS

Central Nervous
System
(CNS)
• Brain
• Spinal Cord

❖ Process sensory input


❖ Generates motor output
Anatomy of CNS
Meninges
Three layers of protective cover surrounding
the brain and spinal cord
- Dura Mater
(thick and tough)

- Arachnoid Mater
(web-like thin membrane)

Subarachnoid space
(CSF, trabecular)

- Pia Mater
(thin membrane held tightly to the cortex )
Anatomy of The Brain

Forebrain
• Cerebral Cortex
(cerebrum)
(Thought and Action
- Consciousness
- Thinking
- Motor skills
2 hemispheres (R and L)
connected by the Corpus
callosum

https://humanbiologybrain.weebly.com/corpus-
callosum.html
https://www.mayoclinic.org/tests-procedures/epilepsy-surgery/multimedia/brain-
hemispheres/img-20008029
Anatomy of The Brain

Cerebrum
- Consciousness
- Thinking
- Memory
- Motor skills
- Sensory information

https://www.howitworksdaily.com/wp-content/uploads/2015/11/brain-diagram-parts-labeled.jpg
Anatomy of The Brain

Brainstem
• Midbrain
(complex structure of neuron
clusters)
- Hearing
- Movement
• Pons
(connection between midbrain
and medulla, origin of 4 cranial
nerves)
- Tear Production
- Chewing
- Focus vision, blinking
• Medulla Oblongata
- heart rhythm, https://www.physio-
pedia.com/Brainstem

- breathing
- blood flow
Anatomy of The Brain

Limbic System
• Thalamus
- relay sensory information
to the cortex
• Hypothalamus
- regulate pituitary gland
(endocrine activity, sleep,
hunger)
• Amygdala
- regulates emotions
- contains many opiate
receptors implicated in rage,
fear, sexual feelings
• Hippocampus
https://www.simplypsychology.org/limbic-

- memory forming system.html

- storing information
- connects memories with
senses
Anatomy of The Brain

Pituitary gland
• Small gland (the size of a pea)
• Located posterior to the bridge of the nose
• Link between the nervous system and endocrine system
- Releases many hormones that affects growth, metabolism,
sexual development, development of reproductive systems
- Connected to the hypothalamus Cerebellum

Cerebellum
• “Little brain”
• It has 2 hemispheres and highly folded structure
- Coordinates voluntary motor movements
- maintains balance, equilibrium

https://www.timeofcare.com/hypothalamus-pituitary-hormones-and-their-
functions/
Anatomy of CNS

Gray matter: formed by the neurons cell body (soma)


White matter: axons wrapped in myelin
https://ranzcrpart1.fandom.com/wiki/Lateral_ventricle
s

Interconnected system of cavities filled with cerebrospinal fluid (CSF)


Anatomy of PNS

Peripheral Nervous System


(PNS)
• Peripheral Nerves
• Cranial Nerves (12 pairs)
• Spinal Nerves (31 pairs)

❖ Afferent sensory communication with CNS


❖ Efferent motor output from CNS
Anatomy of PNS
Cranial Nerves

The brain has 12 pairs cranial nerves


• I and II come from the cerebrum
• III-XII originate from the brainstem
Anatomy of PNS
Spinal Nerves
There are 31 pairs of spinal nerves that emerge between spinal
vertebrae
Autonomic Nervous System

https://www.youtube.com/watch?v=GFrHKUi0tnI
Relevant Cat Video

https://www.youtube.com/watch?v=y8iYsmakI0w&embeds_referring_euri=https%3A
%2F%2Fhubblecontent.osi.office.net%2F&source_ve_path=Mjg2NjY

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