Lecture 2- Neurons and glia

Question 1

What is the role of neurons?

Answer 1

• Neuron is a key cell • 10 to the 11 neurons in human central nervous system •Neurons responsible for all “interesting phenomena? • Consciousness, self awareness, memory, emotion,planning • Control skeletal muscle, viscera and glands • Provide sensory input

Question 2

What do glia mainly do?

Answer 2

-support neurons

Question 3

What are some ways in which we can classify neurons?

Answer 3

• by function (excitatory vs inhibitory) - by neurotransmitter (gluatamate, GABA, cholinergic etc.) - by projection (projection neurons vs interneurons) -by shape (basket cells, chandelier cells) -by system (motor, sensory, autonomic) -all are valid approaches and there are many more ways of classifying neurons

Question 4

What are the classes of neurons and the associated neurotransmitters?

Answer 4

1. Cholinergic (Acetylcholine) 2. Glutamatergic etc. (Glutamate, GABA etc.) 3. Noradrenergic etc. (Noradrenaline, 5-HT etc.) 4. Peptidergic (Endorphins, SP, etc.) 5. Purinergic (ATP and adenosine)

Question 5

What is neuronal morphology like?

Answer 5

-very variable -dendrites= inputs -axon= outputs -cell body is the energy powerhouse supplying the rest of the neuron -variety of standard shapes -morphologically highly specialised

Question 6

What is a neuron?

Answer 6

• a protein producing cell - uses specialised proteins for all sorts of things - larger nucleus than most other cells as their DNA is unwrapped and accessible (Nissl bodies= rough ER, and free ribosomoes= these are so big that they actually stain!) -proteins are required for ion channels, receptors and the cytoskeleton

Question 7

What is the importance of the cell membrane in a neuron?

Answer 7

-neuronal cell membrane is specialised for electrical activity -all cells have some sort of e difference across their membranes but neurons put theirs to work -the membrane can carry graded potentials and action potentials -requires energy expenditure to set up and maintain potential differences (ATPases drive ion flux)

Question 8

What is a graded potential?

Answer 8

-passive electrotonic spread of current = local signal

Question 9

What is an action potential?

Answer 9

-propagates long distances and requires specialised voltage-sensitive ion channels

Question 10

What are the characteristics of dendrites?

Answer 10

-increase surface area for synaptic input -up to 10 000 inputs on a large neuron -lack major organelles -they increase the surface area of the membrane, means of harvesting information = the more surface area= the more info it can receive -in brain lot of neurons will have 10s of inputs -they lack features, it is the membrane that is important

Question 11

What are the characteristics of an axon?

Answer 11

-over a metre long -carries AP -AP can be generated in cell body (axon hillock) or at tip of axon (for sensory neurons= dorsal root ganglia)

Question 12

What is the volume distribution of neural components in a neuron?

Answer 12

-high proportion of total cell volume is in axons and dendrites -random damage often involves axon not the cell body -20 um diameter of the cell body and 30cm axon

Question 13

How are neurons packed in the CNS?

Answer 13

-incredibly tightly, like a pack of tangled spaghetti

Question 14

What does the shape of a neuron depend on?

Answer 14

• the complex shape depends on cytoskeleton

Question 15

What are the 3 main components of the cytoskeleton?

Answer 15

• actin - intermediate filaments - microtubules - same classes of components as in any cell but neurons made it a crucial and specific part of the cell

Question 16

What are the characteristics of actin?

Answer 16

-dynamic assembly/ disassembly allows shape changes and movement (e.g. spines and growth cones) -actin forms filaments from globular subfilaments and can disassemble just as quickly -the little bump on left= spines= input (excitatory) -actin forms growth cone= the growth cone can go on its own, axons are pulled by it to grow -grows spines even in the space of hours

Question 17

What are the characteristics of microtubules?

Answer 17

-dynamic (rapid assembly/disassembly) -made of protein tubulin -have microtubule associated proteins (MAPs) -used for shifting things, like a railway

Question 18

What are the characteristics of intermediate filaments?

Answer 18

-permanent (much more), not dynamic protein filaments -neurofilaments are the major type present in neurons -in all processes -play a crucial role in establishing the basic shape of the cell

Question 19

How does axon transport work?

Answer 19

-have a long axon that needs nutrients etc. from the cell body so need a way of transporting these -microtubules are basis for axoplasmic transport -transports material from cell body to axon and dendrites and vice versa -moves membrane bound components by fast transport (400mm (40cm)/day)) and soluble material by slow transport (4mm/day) -fast transport is microtubule dependent and uses kinesin

Question 20

What is the retrograde axonal transport?

Answer 20

-have to get the material back from the axon to the cell body fro recycling etc. -damaged organelles brought back to cell body for recycling by retrograde axonal transport -samples of the local environment also brought back -some viruses (herpes, chicken pox) and bacteria (tetanus) exploit the retrograde transport

Question 21

What are the characteristics of the axon terminal?

Answer 21

-the axon terminal is where a signal passes from neuron to the target cell -the point of transmission is a specialised structure, the synapse -the information that the cell body is generating can be passed on= this is happening at the end of the axons -when AP reaches the terminal it starts a mechanism by which the information is passed on -via the synapse

Question 22

What are the possible target cells for neurons?

Answer 22

-the target cell can be another neuron or an effector cell (muscle or secretory cell) -targets are a variety of cells -neuro-neuronal synapse/ neuromuscular synapse

Question 23

What does a synapse (EM view, axo-dendritic) look like?

Answer 23

-the synaptic cleft is about 20nm

Question 24

What are the characteristics of synaptic vesicles and the synaptic density?

Answer 24

• vesicles contain neurotransmitter
• the presynaptic density contains the elements necessary to dock and exocytose the vesicle
• the postsynaptic density contains receptors that respond to the neurotransmitter
• mainly supplied by axonal transport
• the binding of the neurotransmitter to receptor gets the response

Question 25

How does initiation of neurotransmitter release happen?

Answer 25

-vesicle exocytosis is Ca2+ dependent -voltage gated Ca2+ channels in the terminal open when an AP invades -AP triggers a Ca2+ spike -the activity of a neuron is mostly electrical but at the synaptic cleft it is chemical

Question 26

How does the termination of neurotransmitter action happen?

Answer 26

-the signal as brief as possible= so do not have to wait until you can transmit again -can speed things up by having enzymes or by having a re-uptake system and recycle (so you are faster than diffusion) -neurotransmitter diffuses almost instantly to the post-synaptic membrane -the post-synaptic effect is limited by: the diffusion of transmitter out of the cleft; destruction of transmitter by specialised enzymes; re-uptake of the neurotransmitter by the axon, target cell or glial cell

Question 27

What is the neuronal energy budget?

Answer 27

• energy budget for rat cerebral cortex:
• dominated by information transfer processes, synapses most important
• can differ between neurons
• need energy constantly, that is why you get brain damage if you don’t breathe even for a few minutes
• budget of a neural cell, housekeeping is only a 1/4 of the energy, which is less than in other cells
• very demanding energetically

Question 28

What are the brain metabolic demands?

Answer 28

-brain is only 2% of total body mass and consumes 20% of oxygen and 25% of glucose -very sensitive to loss of blood flow (O2 and glucose) as few energy reserves -glucose obligatory brain energy substrate (newborn can use ketone bodies) -can burn lactate or pyruvate (and some other metabolic intermediates) but these don’t cross blood brain barrier well -brain can only use glucose but neurons are bad at metabolising glucose so the glial cells convert it into lactate and pyruvate which the neurons metabolise well

Question 29

What is meant by activity-dependent vasodilation in CNS?

Answer 29

-local activity in CNS leads to local increase in blood flow (increases glucose and O2 availability) = to support the active neuron/s -basis for fMRI and PET functional imaging -MRI detects changes in local oxyhaemoglobin seen as Blood Oxygen Level Dependant (BOLD) signal

Question 30

What are the 3 types of CNS glial cells and their general functions?

Answer 30

1. Astrocytes: help neurons survive, provide structural and metabolic support, take up excess K+ 2. Oligodendrocytes: insulate axons (myelination) 3. Microglia: defence cells

Question 31

What are the 2 types of glial cells in the PNS?

Answer 31

-Schwann cells (myelination) and satellite cells (similar to astrocytes in their function)

Question 32

What are the characteristics of astrocytes?

Answer 32

-have many processes -some processes associated with blood vessels (astrocyte end feet), others with dendrites and synapses -individual astrocytes occupy non-overlapping territories, connected by gap junctions -aways around a blood vessels around the synapse the glial cells wrap around it -so synapse it a 3 part structure -it doesn’t work if astrocyte is not there -astrocytes have territories, 1-1 no overlap -fill out the brain -most of the brain is the astrocyte processes

Question 33

What are the roles of astrocytes?

Answer 33

-revolution in understanding their roles as of late -multiple roles in supporting neurons and synapses -involved in: -blood vessel dilation in areas of neuronal activity -neuronal energy supply -synaptic plasticity -neurotransmitter recycling - K+ homeostasis -water homeostasis - oxidative stress protection - injury response and recovery

Question 34

What is the role of astrocytes in blood vessel dilation?

Answer 34

-astrocytes link synaptic activity to increased blood flow -exact messenger is still controversial -caged calcium release in astrocytic end feet leads to vasodilation -EET (epieicosatrienic acid= arachadonic acid metabolite)

Question 35

What is the role of astrocytes in neuronal energy supply?

Answer 35

-neurons happy to metabolise lactate -astrocytes generate lactate from glucose via glycolytic pathway (glycolytic pathway surpressed in neurons) -lactate appears in extracellular space, stimulated by glutamate -neurons have a very low ability to metabolise glucose, the main energy supply of the brain

Question 36

What are the glial cells in the periphery?

Answer 36

-satellite cells support nerve cell bodies in peripheral ganglia (collections of neurons outside the CNS) -Schwann cells support axons in peripheral nerves

Question 37

What are nerves?

Answer 37

-axons bundle together to form nerves -nerves exist outside the CNS -contain Schwann cells as well as axons -wrapped in connective tissues

Question 38

What are the characteristics of myelination?

Answer 38

-oligodendrocytes and some Schwann cells are responsible for myelinating axons in CNS and PNS -speeds up conduction (as does axonal diameter) -one axon per Schwann cell, many axons per oligodendrocyte -AP velocity is proportional to axonal diameter -myelination is another way of increasing conduction velocity -myelination involves a glial cell -a glial cell (oligodendrocyte or Schwann cell) wraps around axon and lays down myelin in the glial cell membrane -the yellow is the wrapping -wrap in the cell membrane (oligo or Schwann cell layer)

Question 39

What are the Nodes of Ranvier?

Answer 39

-oligodendrocytes or Schwann cells myelinate successive lengths of an axon -leave a gap= Node of Ranvier

Question 40

What are the characteristics of the Microglia?

Answer 40

-CNS is immune privileged -microglia are local defence cells from bone marrow -5-20% of cells in mouse brains -resemble macrophages (phagocytic) -activated by inflammation, injury= upregulate cytokines/growth factors -may play a role in development and disease (lack of microglia alters mouse behaviour)

Question 41

What is the cerebrospinal fluid?

Answer 41

-extracellular fluid of brain different to body -CSF low in K+, Ca2+, little protein

Question 42

What is the blood brain barrier?

Answer 42

-brain and spinal cord walled off from rest of body by blood brain barrier -BBB at level of capillaries -prevent free diffusion of most blood-born substance into brain -lipophilic substances penetrate easily by diffusion (etoh, nicotine, heroin) -most other entry by active transport