How Real Neurons Work.

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How Real Neurons Work.

• Computational Neuroscience

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The Neuron Overview
Thanks to Ramon y Cajal for the Neuron doctrine.
(v. reticular theory). Principles of Dynamic
Polarization Signals flow only in one
direction. Principle of Connectional Specificity
Neurons dont make random connections. These
doctrines are now being called into question.
http//www.stewartartists.com/Pages/jjani_pc/jjnrn
s_pc.html
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Overview (2)
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Inside a Neuron.

• Most differentiated cells in the body.
• Neurons develop from epithelial cells.
• Proteins are synthesised in the cell body.
• They are modified in the ER and Golgi complex and
  exported along the axon.

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Classification of Neurons.
Unipolar Invertebrates. Bipolar Retina,
Olfactory epith., Multipolar e.g. motor
neuron, pyramidal cell, perkinje cell.

1. The Cytoskeleton determines shape of neuron,
   (disrupted in Alzheimers disease).
2. Dynamic microtubules and microfilaments.

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The Resting Cell Membrane

• Ionic concentration gradient established by Na/K
  ATPase Pump (100 ions/s).
• K channels allow K to diffuse freely at a certain
  rate.
• K leaves the cell, so making the outside positive
  and the inside negative.
• This is self-limiting, as the positive external
  charge opposes the further efflux of K
• I.E 2 forces Channel Driving Force, Electrical
  Driving Force, when balanced we have the
  Equilibrium Potential of K .

http//www.du.edu/kinnamon/3640/memb_pot_1.html
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Ion Channels

• Ion Channels are crucial for rapid membrane
  potential changes.
• Ion Channels are proteins that span the cell
  membrane.
• Q. How can a water-filled channel conduct at high
  rates and yet be selective to ions surrounded by
  their waters of hydration? A.

• PROPERTIES.
• Conduct Ions.
• Recognize and select specific ions.
• Open and close in response to specific
  electrical, mechanical or chemical signals.
• Rapid rate of flow 108 /s
• Opening and Closing of a channel involves
  conformational changes.

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The Action Potential

• http//www.blackwellscience.com/matthews/channel.h
  tml

An Action Potential is due to channels opening
and closing in a voltage dependent manner. Na
channels open above a threshold voltage.
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The Sodium Channel
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The Ceylon Puffer Fish
Tetrodotoxin injected by Hodgkin and Huxley to
block Voltage-gated Na Channels.
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Cocaine
From coca leaves was the first anaesthetic, and
also blocks Na channels with lower affinity and
specificity than tetradotoxin.
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The K Channel

• An outward K current increases the
  repolarization rate of the action potential

Using Brownian dynamics simulations, we follow
the trajectories of interacting ions in the
potassium channel. With a fast supercomputer, we
simulate the motion of 26 potassium ions and 26
chloride ions interacting through the
intermolecular potential. Here we apply a
potential difference across the channel such that
inside is positive with respect to outside. The
motion of each ion during each discrete time step
is determined by, first, the net electrical force
acting on it secondly, the frictional force and,
finally, random force originating from incessant
collisions of the ion with its surrounding water
molecules.

1. Variations in the properties of voltage-gated ion
   channels increase the signaling capabilities of
   neurons.
2. Gating of voltage gated ion channels can be
   influenced by cytoplasmic factors, e.g. with Ca2
   channels.

An energy profile can be calculated based on
molecular structure.
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The Axon Hillock
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Propagation of Action Potential
Is forwards, because of the inactivated Na
channels. AP travels at 80m/s

• PASSIVE ELECTRICAL PROPERTIES OF NEURONS
• Membrane Resistance determines the magnitude of
  passive changes in membrane potential. Related to
  ion channel.
• Membrane Capacitance prolongs the time course of
  electrical signals. Related to surface area of
  cell.
• Membrane and Axoplasmic resistance affect the
  efficiency of signal conduction.

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Salutatory Conduction
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Chemical Synaptic Transmission

• When AP reaches a neurons terminal
• It stimulates neurotransmitter release.
• Output signal is graded, amount of NT released is
  determined by the number and frequency of the
  action potentials.
• After release, NT diffuses across the cleft to
  receptors on the post-synaptic neuron. Binding
  then results in the post-synaptic cell generating
  a synaptic potential.

The sign of this synaptic potential depends on
the type of receptors.
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Pre-Synaptic Mechanisms

• Action Potential reaches Synapse.
• Synaptic terminal is depolarized.
• Voltage sensitive calcium channels open.
• Calcium enters synaptic terminal.
• Release of chemical neurotransmitter

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Neurotransmitters Are Kept in Vesicles.
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Mechanism of Vesicle Docking.
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Neurotransmitters.
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Amanita muscaria
A Muscurinic Agonist. Stimulates one of the
receptors that AcetylCholine binds to.
The Black widow spider (Latrodectus) is so toxic
because of massive release of acetylcholine from
neurones.
Nicotine is a Nicotinic receptor agonist.
Atropia Belladonna is used to achieve mydriasis,
it has atropine which is an antagonist of
muscarinic receptors
Sweating, salivation, abdominal cramps,
bradycardia
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Post-Synaptic Mechanisms

• Neurotransmitter binds to receptors.
• Change in ionic permeability of post-synaptic
  cell.
• Change in membrane potential of post-synaptic
  cell.
• The same neurotransmitter can have different
  effects depending on the post-synaptic receptors
  present, i.e. inhibitory or excitatory.

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Many Types of NT Receptor Exist.
1. Ionotropic 2. Metabotropic
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Dendritic Spines.
The video clip shows miniature synaptic calcium
transients visualized with the fluorescent
calcium probe (fluo-3) in a spiny cultured rat
cortical neuron dendrite. The image shows
activity over a 10 sec period.
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THE END