• The brain fills most of the brain space inside the skull

• The brain is not directly attached to the skull, and floats in the CSF

• The brain is bilaterally symmetrical

• Corpus callosum: only part of the brain where the left and right hemispheres of the brain are connected

• Thalamus, just above brain stem: The primary function is to relay a motor and sensory signals to the cerebral cortex

• Pons: It connects the cerebrum with the cerebellum, works together with medulla

• Pons and medulla are important for respiration

• Medulla: responsible for involuntary functions (respiration, vomiting, cardiac)

• Temporal lobe: Auditory cortex

• Grey matter = somas and dendrites

• White matter = myelinated axons

  • Myelinated = a sort of insulation around the nerve, which makes it possible to have an action potential

  • They are fatty lipids and thus appear white

• Grey is on the inside for the spinal chord, but on the outside for the brain

• The two cerebral hemispheres are effectively, separate from each other, with only a major linking matter tract, the corpus callosum, and some minor ones including the anterior commissure

• Cerebral cortex is structures as a thin sheet, about 2.5mm thick. To fit the max surface area of cortex in the brain, it is “crumpled up” which gives rise to the gyri and sulci

• The folds are called sulci, the bumps are called gyri

• The ventricles are fluid-filled spaces inside the brain, they make up only a small part of the total volume in a healthy brain

• The spinal chord is the body’s major pathway for ascending and descending information

  • Everything has to go through the spinal chord, both up and down, to the brain

• Cortex has grey matter on the outside surface

• Note that much of the organisation of the nervous system is crossed: the sensory inputs from the right side of the body are processed by the left cerebral hemisphere

• Brain and spinal chord = CNS

• Can divide into the afferent and efferent division

  • They make up the PNS

• Afferent division = all the input / the sensory (all signalling from internal organs) stimuli from the periphery to the CNS

• Efferent division = The output / reaction from the central nerves to the PNS. Can be divided into:

  • Autonomic nervous system: involuntary movement. Divided into sympathetic nervous system (flight or fight) vs parasympathetic nervous system (rest and digest)

    • There is a balance between sympathetic and parasympathetic nervous system

  • Somatic nervous system: voluntary movement.

    • Involves motor neurons and skeletal muscles

• Main brain divisions (anatomically) - anterior and lateral view

• Primary Motor Cortex: once you have decided you will do some sort of voluntary activity, and it has been coordinated in the pre-motor cortex, this is where the signals to execute the movement occur

• Somatosensory cortex: Touch, temperature, pain, vestibular system

• Primary visual cortex: receives, integrates and processes all the visual information from your eyes (the retina)

• Primary auditory cortex: in the temporal lobe, receives input from ears and processes the signals

• Limbic association cortex: where emotions are processed, memory, how you motivate yourself

• Brokers area = speech formation, Warnicke’s area = speech understanding

  • Broker’s area processes this in sensory information that comes into the temporal cortex

    • Devises a plan for speaking (does not allow you to speak, but allows you to plan what you are going to say, what actually allows you to speak is motor cortex)

  • Warnicke’s area is important for understanding speech, so it is hard to understand a word and be able to communicate if this area is damaged

• Spinal chord has a very precise organisation

• Dorsal = towards the back AKA posterior, it is the sensory side of the spinal chord

  • Dorsal side of spinal chord have the afferent axons, so all sensory inputs from periphery are ascending to the brain via the dorsal root ganglion

• Ventral = towards the front AKA anterior

  • Efferent axons, so the motor outputs, signals to periphery to do some sort of actions ; motor neurons are engaged

Cellular units of the nervous system

• The neuronal doctrine

  • NB: Golgi staining technique = staining technique for neurons

  • The neuronal doctrine had four principles

    1. The neuron is the structural and functional unit of the nervous system

    2. Neurons are individual cells, which are not continuous to other neurons, neither anatomically nor genetically

    3. The neuron has three parts: dendrites, soma (cell body), and axon. The axon has several terminal aborizations (AKA just axon terminal), which make close contact to dendrites or the soma of other neurons

    4. Conduction takes place in the direction from dendrites to soma, to the end aborizations of the axon

• Action potential is generated at axon hillock

• Myelin (white fatty lipid that insulates the action potential) allows for fast conduction of the axon, like a cable’s plastic casing, if there was no casing you would lose all the signals, and the action potential would be so much slower

• Neurons come in different shapes and sizes

  1. Unipolar

     1. Only present in vertebrates, humans do not have them.

  2. Bipolar

     1. Soma in the middle, two distinct structures extending from the soma (one is the axon, one is a dendrite)

     2. Not as common, they are in specific parts of the body

  3. Multipolar

     1. Most common, lots of in the nervous system

     2. Soma, axon, and high number of dendrites

  4. Pseudounipolar

     1. Its one axon branches out into 2, it looks like a unipolar

• BUT there are functionally 3 types of neurons

  1. Sensory

  2. Integrative

  3. Motor

• Several sorts of them, and outnumber neurons by 10:1

• Help blood brain barrier, energy supply, clean up damages when something happens

• Astrocytes (green) recycle neurotransmitters, is really important for homeostasis and energy supply (glucose and oxygen)

  • NTs need to be recycled (re-uptaken)

• Dorsal = towards the back AKA posterior, it is the sensory side of the spinal chord

  • Dorsal side of spinal chord have the afferent axons, so all sensory inputs from periphery are ascending to the brain via the dorsal root ganglion

• Ventral = towards the front AKA anterior

  • Efferent axons, so the motor outputs, signals to periphery to do some sort of actions ; motor neurons are engaged

Cellular units of the nervous system

• The neuronal doctrine

  • NB: Golgi staining technique = staining technique for neurons

  • The neuronal doctrine had four principles

    1. The neuron is the structural and functional unit of the nervous system

    2. Neurons are individual cells, which are not continuous to other neurons, neither anatomically nor genetically

    3. The neuron has three parts: dendrites, soma (cell body), and axon. The axon has several terminal aborizations (AKA just axon terminal), which make close contact to dendrites or the soma of other neurons

    4. Conduction takes place in the direction from dendrites to soma, to the end aborizations of the axon

  

  Neuron Diagram

• Action potential is generated at axon hillock

• Myelin (white fatty lipid that insulates the action potential) allows for fast conduction of the axon, like a cable’s plastic casing, if there was no casing you would lose all the signals, and the action potential would be so much slower

• Neurons come in different shapes and sizes

  1. Unipolar

     1. Only present in vertebrates, humans do not have them.

  2. Bipolar

     1. Soma in the middle, two distinct structures extending from the soma (one is the axon, one is a dendrite)

     2. Not as common, they are in specific parts of the body

  3. Multipolar

     1. Most common, lots of in the nervous system

     2. Soma, axon, and high number of dendrites

  4. Pseudounipolar

     1. Its one axon branches out into 2, it looks like a unipolar

• BUT there are functionally 3 types of neurons

  1. Sensory

  2. Integrative

  3. Motor

Glial Cells

• Several sorts of them, and outnumber neurons by 10:1

• Help blood brain barrier, energy supply, clean up damages when something happens

• Astrocytes (green) recycle neurotransmitters, is really important for homeostasis and energy supply (glucose and oxygen)

  • NTs need to be recycled (re-uptaken)

  • Microglial cells are immunity cells, when there is damage in the brain, these cells ‘eat’ what does not need to be there, so the cells don’t die

  • Oligodendrocytes make myeline for neurons in the CNS

  • Schwann cells are the same but for the neurons in the PNS

• Glial cells also respond to injury - “activation phenotype”

• Membranes around the brain - meninges

• These are all cranial meninges

  • Dura mater

    • Closest to skull

  • Arachnoid mater

  • Pia Mater

    • Closest to brain

Role of CSF

• Supports the brain, allowing it to float inside the skull ; provides some cushioning

• Provides an appropriate chemical environment for the brain by supplying nutrients and removing waste products

• Allows for chemical signalling

• CSF volume ~ 150mL, but ~500mL produced/day

• Composition of CSF is similar to plasma but with less protein

• The brain does not store energy, so needs a near-continuous supply of blood to deliver oxygen and glucose. An interruption to the cortical blood flow lasting 10 seconds will produce unconsciousness, and one lasting several minutes will cause permanent brain damage

• brain barrier - selectively leaky

  • The blood-brain barrier refers to the restricted permeability of brain capillaries. Astrocytes work with the capillary cells to make the tight functions less leaky.

    • Main purpose: protect brain from toxins

• What is an action potential?

  • Is an all or nothing electrical depolarisation of the cell membrane, triggered by the membrane depolarising past a threshold

    • Needs to get past the threshold, otherwise no action potential generated

  • Depending on strength of stimulus, you an get different responses (graph 1), so strength needs to be high enough to reach the threshold

    • Then, depolarisation occurs

  • Action potential = change in membrane potential/change in voltage

• Voltage-gated Na+ and K+ channels & the AP

• Na+ channel

  • Ions go through cell membrane, all cells neurons and other cells in the body all have this plasma membrane, which contain proteins and ion channels

  • At resting membrane potential, gate is closed, unless a stimulus brings resting membrane potential to a positive potential, then gate opens

  • Initiation of stimulus (red) → Activation gate opens and allows sodium to enter (allows it to go from threshold to peak potential as all the ions rush in)

    • Reaching this threshold actually brings about the action potential

  • Once you reach peak, the channel closes and stops Na from coming in and is deactivated and is unable to open

    • It is NO longer capable of opening, it is inactive. This is the inactivation gate

    • This means the inside of the cell becomes more negative and goes down to resting membrane potential again

  • Once it reaches resting membrane potential again, it is still closed, but can be activated again

• K+ Channels

  • K+ wants to leave, but cannot because it is at resting potential and closed

    • Once open, this allows potassium to go out and makes the inside of the cell more negative. This is what allows the cell to go from its peak back down to resting membrane potential

• Changes in the membrane’s ion selectivity underlie the action potential

  • The membrane can allow different ions to go in at different times (see above)

  • Resting membrane potential is close to equilibrium potential for K+, which means the membrane is more permeable to K+

    • This means that K+ leaves the cell, making the cell more negative.

  • Membrane becomes much more permeable to sodium as the peak is reached

  • At 3, the membrane is more permeable to K+ again

• What happens to the depolarisation along the axon?

  • Triggering event opens Na+ channels

    • Making membrane more positive

  • Axial spread of depolarisation depends on current flow down the axon interior (dependent on internal resistance Ri) vs “leak” across the membrane (dependent on membrane resistance Rm)

• Active currents lead to regenerating spread of depolarisation

  • Local current flow occurs between the active and adjacent areas

Myelin and Propagation

• Myelination of axons

  • Myeline is formed from insulator cells which wrap their own membrane around the axons of myelinated neurons

    • Improves speed of neurotransmission

  • Derived from Schwann cells (PNS) or oligodendrocytes (CNS)

• Myelination saves time and energy

  • A myelinated fibre has only part of its membrane exposed to the outside environment.

    • Channels are only at high density at the nodes where the action potentials take place

  • This causes saltatory conduction at high speed with reduced metabolic costs

    • Depolarisation happens at nodes of ranvier

• In saltatory conduction the action potential jumps from node to node

  • The action potential typically jumps 2-3 nodes from one depolarisation. This greatly increases the speed of conduction in myelinated axons

The Synapse

• What is a synapse?

  • Neurons don’t touch each other, but rather, interact at contact points called synapses

• Different types of synapse locations

  • Axo-dendritic → Neuron has its axon synapsing onto a dendrite

    • 90% of them are excitatory; they release neurotransmitters that activate the neurons

  • Axo-somatic → Axon synapses to the cell body

    • Largely inhibitory, this means the neuron gets signals to hypopolarise (become more negative) and become more inactive

  • Axo-Axonic → presynaptic inhibition

• Chemical Synapses

  • Uni-directional → one-way flow of information

  • Selective → only affects a single neuron

  • Modifiable → the outgoing response can be amplified or reduced

  • Signal can be inhibitory or excitatory

Pre-synaptic events

• Once AP has travelled along the neuron and reaches the AP terminal, pre-synaptic events occur

1. Neurotransmitter molecules are synthesised and packaged in vesicles

2. AP arrives at presynaptic terminal

3. AP causes the opening of voltage-gated Ca2+ channels, so Ca2+ enters

4. Increasing Ca2+ in the cell triggers fusion of synaptic vesicles with the presynaptic membrane

5. Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell

6. Once bound, receptors activate the post-synaptic cell

7. All the excess NTs are broken down, they are taken up by the presynaptic terminal or other cells, or diffuses away from the synapse

Post-synaptic events

• Simple chemical synaptic transmission

  • Excitatory and inhibitory post-synaptic potentials:

    • Caused by presynaptic release of neurotransmitter

      • EPSP: Transient postsynaptic membrane depolarisation

      • IPSP: Transient hyperpolarisation of post-synaptic membrane potential

• Most common excitatory receptors - Glutamate excites all of them

  • Process: Glutamate (or any NT) is released from the pre-synaptic terminal and packed into vesicles, and then is fused with the pre-synaptic membrane and is released into the synaptic cleft, and then binds onto one of these receptors:

  • AMPA, NMDA, Kainate

    • This activates these neurotransmitters, and this means there are positive ions running through, and it will be more positive inside the cell and EXCITES the cell

    • These are named after the agonists that activate them

  • Glutamate is also used at most synapses that are “modifiable”, i.e., capable of increasing or decreasing in strength.

    • Modifiable synapses make it possible for us to store memories

• Most common inhibitory receptors

  • GABA

    

    • Inhibitory at 90% of the synapses that don’t use glutamate

• What makes a synapse inhibitory or excitatory?

  • A function of both neurotransmitter and receptor

    • The key is what happens to membrane potential

  • Excitation results from depolarisation, which moves the membrane potential away from rest (~ -70mV) and towards threshold for action potential. This EPSP (Excitatory post-synaptic potential) can be caused by opening Na+ channels (e.g. AMPA; cation channels)

  • Inhibition results from hyperpolarisation away from threshold to a more negative potential. This IPSP can be caused by:

    • Opening Cl- channels (e.g. GABAa)

    • Opening K+ channels (e.g. GABAb mediated)