The nervous system

1
The nervous system

• Regulatory systems basic concepts
• Feedback positive and negative
• The nervous system neuron structure
• Signal transmission
• Increasing conduction velocity
• Talking to other neurons The synapse

2
About the exam

• Medium length (Four point) questions 2
• Question 2 was worth 4 points TOTAL
• Mistakenly graded as 4 points for 2b and 2 points
  for 2a.
• Everyone had a grade scratched out and changed
• 4 became 2
• 3 became 1.5
• 2 became 1 etc
• Colligative antifreeze was worth only 1 pt.

3
Longer format questions

• These questions test your command of a concept
• Can you explain it coherently and furnish
  examples?
• Can you apply it to novel questions?
• Theyre not about how smart you are or whether
  you understand when something is explained to
  you.
• They ARE harder, but theyre less random
• Life is not multiple choice!

4
Regulatory systems

• Nervous system ( 2 classes)
• Endocrine system (2 classes)

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Operate through feedback

• Components of a regulatory system
• Some controlled variable (e.g. body temperature,
  blood sugar)
• A set point (e.g. 37ºC, 190 mg glucose /dl blood)
• One or more detectors
• One or more control mechanisms

6
Feedback

• comparing variable of interest with the
  setpoint, adjust control systems accordingly.
• Negative feedback
• A deviation from the setpoint provokes a
  corrective response in the other direction
• Negative feedback promotes homeostasis!
• Positive feedback
• A deviation from the setpoint provokes a response
  in the same direction
• Positive feedback amplifies response to small
  changes!

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Negative feedback - thermostat

• Temperature falls below setpoint
• Thermostat signals Boiler to turn on
• Boiler raises temperature to above setpoint
• Thermostat signals boiler to turn off

Thermometer (detector)
Thermostat (set point)
Boiler (on or off) - effector
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Negative feedback - thermostat

• Note that this type of simple negative feedback
  system inherently produces oscillations around
  the setpoint
• Depends on threshhold sensitivity!

Too hot
setpoint
Less sensitive thresholds
More sensitive thresholds
Too cold
9
Antagonistic systems

• Many forms of negative feedback take place
  through antagonistic systems
• E.g., a house with both a heater and an air
  conditioner active
• Need to integrate these signals appropriately
  (e.g., activating one response suppresses the
  other)
• Achieves a finer level of control than ON/OFF
  regulation

10
Neurons (More weird cells)

• Cell body (with nucleus)
• Dendrites
• Shorter, branching fibers (generally lt 1 mm)
• Bring incoming signals
• Axon
• Long fiber (can be several meters long!)
• These are like cables
• Take signal to next neuron
• Synaptic bulbs
• Contact points between neurons
• Space between contact points synapse
• These are like switching devices

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Anatomy of a neuron
Synaptic bulbs
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Neuron shapes
Processes from cell body?
Typically efferent outgoing signal
Multipolar
Typical of CNS interneurons
Bipolar
Unipolar
Typically afferent incoming sensory signal
Direction of signal
13
Very basic functional map
(Central nervous system)
14
Nerves

• Nerves are bundles of axons
• 100s 1000s of axons
• Cell bodies are aggregated into ganglia, or
  centers of neuron connections
• Axons synapses are directional!
• Like a one-way street only transmit impulses in
  one direction
• Nerves can have axons going in both directions
• Can both transmit and receive information

15
How do neurons transmit signals?
We have the squid to thank for what we know!
Squids have giant axons in their mantles
Big enough to stick an electrode inside

• People have known for 100s of years that the
  signal is electric
• Has to do with changes in charge ratio (measured
  as a voltage) across membranes action potentials

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Membrane potential

• Outside of cell Lots of Na, lots of Cl-
• Inside of cell Lots of K, lots of immoveable
  anions (negatively charged residues on proteins,
  e.g. carboxyl groups)
• Net charge is slightly negative inside, slightly
  positive outside
• Neuronal membranes are relatively permeable to
  K!
• K tends to diffuse out of cell until it starts
  to be repelled by charge
• Balance of concentration potential and electric
  membrane potential

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Balancing potentials
Hi K
Concentration potential
Low K
Outside cell
Inside cell
K flow
K flow
Resting potential of neuronal membrane is
-60mV (inside negative relative to outside)
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The Nernst Equation

• This predicts the resting potential based on one
  ion (K)
• R universal gas constant
• T temperature (kelvins)
• F charge constant (contained by 1 g. of ions)
• K potassium ion concentrations
• At room temperature, this simplifies to 58 log
  10 (Ko/Ki)
• In/out concentration ratio 1/20 predicts
  resting potential of -75 mV

19
The Goldman Equation

• Nernst Eqn doesnt quite get it right (-75mV
  predicted, -60 mV actual)
• Goldman equation predicts resting potential based
  on all 3 major ions
• Each ion concentration is weighted by membrane
  permeability
• This equation predicts potential exactly! Way to
  go, Goldman!

20
Na is NOT happy

• It wants to be inside the cell, based on BOTH
  concentration and charge
• Na would equilibrate at a membrane potential of
  55 mV (Nernst eqn)
• But alas, its desires are foiled by
• Na/K pump
• Impermeability of cell membrane to Na
• Neuron is capable of generating resting
  potentials of -60 to 55 mV based solely on
  membrane permeability to different ions

21
Action potential

• An action potential is a wave of depolarization
  and repolarization that moves across a cell
  membrane
• Cell membrane is studded with voltage gated Na
  channels
• When the membrane depolarizes beyond a threshold,
  Na channels open
• Rush of Na into cell membrane potential
  changes to 55mV!
• Slower K channels open when membrane potential
  peaks, Na channels close
• Rush of K out of cell returns membrane to
  resting potential

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1 resting potential 2 depolarizing stimulus
arrives 3 At threshhold polarity, Na channels
open 4 rapid Na entry 5 Na channels close, K
channels open 6 K rushes out 7 voltage
overshoot! 8 K channels close, cell returns to
resting P
brief refractory period
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Why doesnt cell fill up with Na?

• Changes in Na and K are
• Relatively small
• Highly local
• Quite rapid
• Cause a big effect in a very small area for a
  very short time
• A single AP changes the Na inside a squid
  neuron by lt0.001 - a tiny amount.
• Na/K pumps are always working (although more
  slowly) to restore Na and K
• However, even if Na/K pumps are disabled with
  metabolic poison, squid neuron can generate 1000s
  of action potentials

24
APs work through postive feedback
25
Refractory period

• Axons are refractory to further APs after one has
  passed
• Action potentials cannot go backwards!
• This causes APs to travel in one direction, away
  from trigger point

26
Conduction velocity

• Two major determinants of conduction velocity
• Neuron diameter
• Resistance of neuron membrane to current leak
• Several invertebrate examples of giant neurons
• Squids
• Earthworms
• These tend to be animals with relatively few
  neurons!
• Vertebrates have too many neurons for this
  strategy
• Instead focus on insulating membrane

27
Myelination
Schwann cells A type of supporting cell glial
cell
These wrap around an axon, forming a fatty sheath
myelin
Node of Ranvier
Myelin insulates cell membrane from extracellular
fluid
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Myelination

• Glial cells support neurons
• Schwann cells are a type of glial cell that forms
  myelin
• Wrap themselves around axons to form a sheath
• This prevents membrane from contacting
  extracellular fluid
• Exposed nodes between Schwann cells have normal
  APs
• APs jump from node to node through cytoplasm
• Speed of a myelinated neuron is equivalent to an
  unmyelinated neuron that is 100 times larger!
• If our optic nerves were unmyelinated, they would
  have to be a foot wide to conduct impulses at the
  same speed!