Lecture 3- Cellular physiology of the brain Flashcards
1
Q
Components of the CNS
A
- Network of neurones with supporting glia
- Neurones sense changes and communicate with other neurones (10^11 neurones)
- Glial support, nourish and insulate neurones and remove waste (10^12- 10x as many glial cells than neurones)
2
Q
Types of glial cells (neuroglia)
A
- Astrocytes
- Most abundant glial cell
- supporters
- Oligodendrocytes
- Insulate axons
- Microglia
- Immune response
3
Q
astrocyte functions
A
- Structural support
- Nutrition for neurones through the glucose-lactate shuttle
- Remove neurotransmitters (uptake)
- Control conc of NT- especially important for glutamate (toxic)
- Maintain ionic environment
- K= buffering
- Help to form BBB
4
Q
How do astrocytes help provide energy for neurones?
A
- Neurones do not store or produce glycogen
- Astrocytes can store glycogen
- they produce lactate from the breakdown of stored glycogen which can be transferred to neurones and used to produce ATP which can be used as an energy source of the neurone
- Supplements their supply of glucose
- Glucose lactate shuffle (if supply of glucose low to neurone e.g. if blood supply decreased
5
Q
Glucose lactate shuffle
A
- Astrocyte stores glycogen
- Astrocyte produce lactate from the breakdown of glycogen
- Lactate then shuttled across with H+ via the MCT1 transporter on the astrocyte and the MCT2 transporter on the neuron
- Lactate is then converted to pyruvate
- Pyruvate metabolism releases ATP which can be used as an energy source of the neurone
6
Q
How do astrocytes help buffer K+ in brain ECF?
A
- High levels of neuronal activity could lead to a rise in K+ in brain ECF
- Depolarises neurones- positive feedback effect
- Astrocytes mops up K+ via the sodium and potassium ATP pump, the potassium channel and the Na2ClK co transporter
7
Q
Oligodendrocytes
A
- Responsible for myelinating axons in CNS
- Myelinate more than one axon
- Helps conduction of action potential by lowering capacitance (means that a lower change in ion conc is required to initiate an axon potential)
- Comparable to Schwann cells responsible for myelination in PNS
8
Q
Microglia origin
A
mesodermal
9
Q
function of microglia
A
- Mesodermal origin
- Immunocompetent cells
- Recognise foreign material- activated
- APC
- Phagocytosis to remove debris and foreign material brains main defence system
10
Q
how does the structure of microglia change when they are exposed to a foreign material
A
- In resting stay- dendritic
- In activated state- dendrites swell until dendritic appearance is lost and become phagocytic- enhancing engulfment of foreign material
11
Q
The blood brain barrier
A
Limits diffusion of substances from the blood to the brain extracellular fluid
- Maintains the correct environment for neurones
12
Q
feature of blood brain barrier capillaries
A
- Tight junctions between endothelial cells- forms the BBB
- Basement membrane surrounding capillary
- End feet of astrocyte processes
13
Q
Pathways across the BBB
A
- Water, CO2 and O2 (lipophilic)freely move across endothelial cells
- Substances a such as glucose, amino acids and potassium are transported across BBB
- Glucose – GLUT1 transporter
- K+- potassium channels
- Amino acids
- Some amino acids work as NT so don’t want them to freely cross
- Allows conc to be controlled
14
Q
CNS ‘immune privilege’ more like
A
immune specialised
- Does not undergo rapid rejection of allografts (someone else tissue) like it would someone else
- Immune specialised
15
Q
- Why does the brain have to be immune specialised?
A
- Rigid skull will not tolerate volume expansion
- Too much inflammatory response would be harmful
16
Q
typical response to foreign material in the brain
A
- Microglia can act as antigen presenting cells
- T cells can enter CNS and antigens can be presented by APCs
- CNS inhibits the initiation of the pro-inflammatory T-cell response
17
Q
Typical neuronal structure
A
Four main sections
- Cell soma (body)
- Dendrites
- Axons
- Terminals
18
Q
Neurotransmitter release at synapse
A
- Action potential travels down axons to terminals
- Depolarisation in the terminal opens voltage gated calcium channels- calcium ions enter the terminal
- Vesicles fuse and release NT
- Neurotransmitter diffuses across the cleft and binds to receptors on the postsynaptic membrane
- Response depends on
- Natural of transmitter
- Nature of receptors
- Ligand-gated ion channels
- G-protein coupled receptors
19
Q
Neurotransmitters in the CNS
A
- Many NTs
- Can be divided into three chemical classes
23
Q
main excitatory amino acid NT
A
glutamate
- Over 70% of all CNS synapses are glutamatergic
- Present throughout CNS
28
Q
Ionotropic receptor and fast excitatory responses
*
A
- Excitatory NTs (e.g. glutamate) cause depolarisation of postsynaptic cell by acting on ligand-gated ion channels
- Excitatory postsynaptic potential (EPSP)
- Depolarisation causes more action potentials
31
Q
glutamate receptors role in learning and memory
A
- Activation of NMDA receptors (and mGluRs) can up-regulate AMPA receptors
- Strong, high frequency stimulation causes long term potentiation (LTP)
- How learning and memory occurs
- Ca2+ entry through NMDA receptors important for induction of LTP
35
Q
GABA and glycine receptors
- x
A
- GABAA (ligand gates- ionotropic) and glycine receptors have integral Cl- channels
- Opening the Cl- channels causes hyperpolarisation
- Inhibitory post-synaptic potential
- Decreased action potential firing
- Inhibitory post-synaptic potential
- Also GABAB (metabotropic)- modulatory role
37
Q
Glycine’s role in the stretch reflex
A
- When you hit the patellar tendon the quadriceps muscle is stretched- sensed by stretch receptors in the muscle spindle
- Afferent sensory neurone send impulse to spinal cord and releases glutamate which directly activates motor neurone to release Ach to cause a contraction of the quadriceps
- However, in the reciprocal/antagonistic muscles such as the hamstrings there is relaxation because there is an inhibitory interneuron that is stimulated when afferent receptors of the muscle spindle (when stretch is sensed) stimulates it with Glutamate
- The inhibitory relay neurone then releases glycine which inhibits the motor neurone to the antagonist muscles (hamstring) therefore allows the hamstrings to relax
38
Q
Acetylcholine as a NT
A
- Neuromuscular junction
- Ganglion synapse in ANS
- central NT
- Postganglionic parasympathetic
39
Q
Cholinergic pathways in the CNS
*
A
- Can either be discrete or more diffuse
- Neurones originate in basal forebrain (nucleus basalis) and brainstem
- Give diffuse projections to many parts of the cortex and hippocampus
- There are also local cholinergic interneurons e.g. corpus striatum
- Involved in arousal, learning and memory, motor control
41
Q
Dopaminergic pathways in CNS
A
- Can either be discrete or more diffuse
- Nigrostriatal pathway- motor control
- Mesocortical pathway and Mesolimbic pathway
- Involved in mood, arousal and reward
43
Q
Dopamine therapy and BBB
A
- L-DOPA can freely cross the BBB through the large neutral amino acid transporter
- Converted to dopamine by aromatic amino acid decarboxylase AADC (dopa decarboxylase)
- Converted both in the periphery and the brain (AADC also found in periphery)
- Don’t want excess dopamine in the periphery –> therefore we give Carbidopa which inhibits AADC
- Carbidopa cannot cross the BBB- therefore no central effect
45
Q
NA pathways in the CNS
A
- Cell bodies of NA containing neurones are located in brainstem (pons (locus coeruleus) and medulla)
- Diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum
47
Q
Serotongergic pathways in CNS
A
- Start in the raphe nucleus in the brainstem
- Diffuse projections to the cerebellum and cortex
- Projections to hippocampus and amygdala
