l03 roots - cornell university · pdf filecellular space in synaptic cleft) ... a restricted...
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L03. ROOTS of NEUROETHOLOGY IN CELLULAR NEUROBIOLOGY
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© Carl D. Hopkins Aug. 28, 2011
Announcements
1) Course website: http://courses.cit.cornell.edu/bionb4240/index.htmGoogle Chrome?
2) Writing AssignmentsW1
3) Discussion sectionWednesday 9:05 AM, this room.
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OutlineL03. Roots in Cellular Neurobiology1. Krogh's Principle2. Neuron doctrine3. Neuron as connector, integrator, rectifier, transducer,
logical device, memory storage, circuit.
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“For a large number of problems [in biology] there will be some animal of choice, or a few, on which it can be most conveniently studied.”
—August Krogh, The Progress of Physiology, The American Journal of Physiology, 1929. 90(2) pp. 243-251
KROGH’S PRINCIPLE
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August Krogh Denmark. Nobel Prize 1920. Discovery of capillary motor regulating mechanism
Squid The Discovery of the Giant Squid Axon1936: Young, J. Z. Proc. Roy. Soc. London B. 121:319 (Description of the giant axon of squid, Loligo)
Young thought the these curious structures were blood vessels, but he was able to show that upon stimulation with electrical currents they caused the mantle to contract so he realized they were
John Z. Young F.R.S. 1907-1997Zoologist, Oxford University
contract, so he realized they were nerve fibers.
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Giant nerve fibers in squidBullock and Horridge (1965)
Must See Videos:http://www.science.smith.edu/departments/NeuroSci/courses/bio330/squid.html
A. L. Hodgkin and A. F. Huxley, RESTING AND ACTION POTENTIALS IN SINGLE NERVE FIBRES. Physiol. (London), 104(1945)176.
2 ms
• ability to record intracellular voltage• first voltage clamp (2 electrodes inside: I, V) • ability to perfuse (replace) intracellular ions,
d l t f tit ti d i ti f ti
After the Discovery of Squid Axon
• development of quantitative description of action potentials
• ability to record from both pre- and post-synaptic neurons at giant synapse
“…The squid axon did more for axonology than any other single advance in technique during the previous 40 years.”
Alan Hodgkin (1973) see quote by R. Keynes (2005)
Nerve nets in hydra and jellyfish (Cnidaria)
Nerve net in hydra Neurons in jellyfish
NEURON DOCTRINE
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Santiago Ramon y Cajalused Golgi methodprovided evidence for Neuron doctrinefirst evidence of multitude of cell types, neural circuts
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Kitten cerebellum
Basket endings convincing proof of separate cells.
- basket cell surrounds cell body but does not connect to purkinje cell.
Axons may cross, but not connect.
Each element autonomous (a cell).
Golgi Method
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Calaj’s Neuron Doctrine• The nervous system is
composed of cells: glial cells and neurons.
• Neurons are morphological units.
• Neurons make intimate contacts (contiguous but not continuous)
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continuous).• Cell bodies and dendrites
are conductors, just like axons.
• Dynamic polarization• When there are axon
collaterals, they act together.
• Axons arise in development by neurite outgrowth
Summarized in Nobel speech (1906) - shared with Golgi.
Electron Microscopy Clinches The Neuron Doctrine
First EM: Germany,1930’s.
Fixation of tissues (Palade and Porter, 1950’s)
Palay, Palade, DeRobertis:
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Neurons with distinct membranes at synapses (extra-cellular space in synaptic cleft) (1954-9).
ANALYSIS LEVEL
molecularwhole animal
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subcellular
cellular
circuits
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layout
wiring
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whole machine
components
inside components
software
The Neuron By AnalogyNeuron as a wire.
Neuron as a rectifier.
Neuron as transducer.
Neuron as a connector
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Neuron as a connector.
Neuron as an summing circuit.
Neuron logic.
Neuron as a memory storage device.
Neuron in a circuit.
Neuron as a Wire Neuron Shape: long axon makes long distance, highly
specific contact possible.
Neuron electrical properties: signals travel within a neuron (insulation)
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travel at high speed (propagation)use electric signals (=action potentials)
Branching: permit elaborate connectionsdivergenceconvergence
Neuron ShapeAxon serves as information
conduit.-- long distances-- efficiently packaged
Consider a scale model of motor neuron (soma = 100
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microns; axon = 1 m)(ratio = 1:10,000)
Axons, longitudinal view Axons, cross section
Dye filled axons
Axon bundles make up nervesDorsal Roots (sensory)
sensory
white matter
gray matter
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Ventral roots (motor)
spinal cord
ganglion (cell bodies)
Nerve Cells Communicate with Targets Using Electric Signals1) Resting neurons are electrically polarized.
- resting potential
2) A i i l i d b
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2) Action potentials: transient events caused by opening of ion channels in membrane. Propagates down axon.
3) Slow potentials: originate in sensory receptors, and at synapses. Local, do not propagate.
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Nerve cell at rest has a voltage across its membrane = resting potential
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Action PotentialsThe Action Potential
(spike): – Transient
(1 millisecond duration)–“de-polarization”
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p–peak voltage = +55 mV
inside(mainly due to influx of Na+ ions)
–All or None (threshold)–propagates along axon
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Some Ion Channels in Nerve Membranes are Voltage-Dependent• Ion selective AND Voltage dependent (opening controlled by voltage)
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outsidecell
cell at rest (-70 mV) cell partly depolarized (-30 mV)
cell depolarized(+55 mV)
The Sodium Channel
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Potassium Channels
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Structure worked out in 1998 (Doyle et al. –Roderick MaKinnon lab)
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How the action potential propagates
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Propagation Velocity
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• Measuring velocity with two electrodes• velocity = distance / time• myelinated nerve: 10 to 100 m/sec
t
Neuron as Rectifiers
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SYNAPSESExcitatoryInflux of cations (+ charge)
cause membrane depolarization
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Neuron as a TransducerHow do signals get started in
neurons?sensory receptor neuron
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Crayfish Stretch Receptor Neural code for stretch intensity is the frequency of nerve impulses
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Adaptation
SA
RA
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Membrane channelsMSC mechanosensitiveNa – sodiumK – potassiumCl - chloride
Bo Rydqvist, Jia-Hui Lin, Peter Sand, Christer Swerup (2007) Mechanotransduction and the crayfish stretch receptor. Physiol. & Behavior. 92: 21-8.
Pharmachological blockers can sort out the various ion channels responsible for the receptor potential, adaptation, and spikes.
38Bo Rydqvist, Jia-Hui Lin, Peter Sand, Christer Swerup (2007) Mechanotransduction and the crayfish stretch receptor. Physiol. & Behavior. 92: 21-8.
39Wine, J. (1984). J. Experimental Biology. 112:283-319.
SummationSynapses: synaptic potentials sum on the
post-synaptic cell, providing for:-- spatial summation:-- temporal summation: -- subtraction:
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Fine Tuning the Neuron as Integrator (summing network)
Excitatory synapse generates a depolarizing potential.
Membrane voltage decreases exponentially with distance
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with distance.
Rise time increases with distance.
Consider a synapse on a dendrite.
Neuron as ConnectorSome neurons serve to
relay signals from one cell to another.’
Signal is relayed from input to the output
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Neuron LogicAND logic
Output spike only if 1 + 2 are active at same time.
OR logicOutput spike if either 1 or 2
ti2
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are active
NOT logicOutput spike if 1 OR 2, but NOT 3
1
2
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Neuron MemorySynapses retain a
memory of recent events.
Depression: recent activity leads to decrease in response
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decrease in response.
Facilitation: recent activity leads to increase.
Pre-synaptic inhibition.
Pre-synaptic facilitation.
Changing the Strength of a Synapse
• Fatigue– depletion of synaptic transmitter
• Habituation– decrease in amount of transmitter released, but not due to fatigue
• Sensitization
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– increase in amount of transmitter released
Changing the Strength of Synapses
• Pre-synaptic excitation– a synapse on a synapse
(primes synapse to be stronger).
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• Hebbian Learning– NMDA receptor for
glutamate: synapse is made stronger if activated when cell already depolarized
Neural Circuitsand Behavior
cell body
4. motorneuron
3. synapseTracing circuitry of neural connections leads to understanding of how behavior is influenced by neuronal action.
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stimulus
1. sensory transduction
2. sensory dendrite
neuron
muscle
Neural Circuits and Behavior
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Perception correlates with characteristics of neural circuit.
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Neuronal Activity is both Necessary and Sufficient
A) Correlation between behavior and activity of a particular neuron (LGI)
B) Sufficient: artificial
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stimulation of the neuron causes both a spike, and the behavior.
C) Necessary: if the neuron spike is blocked, the natural behavior is blocked, even though stimulus is OK.
Complex Behavior, Complex CircuitsStomatogastric Ganglion of
Lobster.A restricted neural network (30
cells).Controls muscles of gastric mill
and the pylorus (movements involved in griding of food
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involved in griding of food and of digestion).
The PYLORIC muscles and patterns of contraction.
The End
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43-52.Hodgkin, A. L. and Huxley, A. F. (1952e). A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (London) 117, 500-544.Hodgkin, A. L., Huxley, A. F. and Katz, B. (1952). Measurement of current-voltage relations in the membrane of the giant axon of Loligo. J Physiol116, 424-48.Keynes, R. (2005). J. Z. and the discovery of squid giant nerve fibers. Journal of Experimental Biology 208, 179-180.Krogh, A. (1929). The progress of physiology. American Journal of Physiology American Journal of Physiology 90, 243-251.MacKinnon, R., Cohen, S. L., Kuo, A., Lee, A. and Chait, B. T. (1998). Structural conservation in prokaryotic and eukaryotic potassium channels. Science 280, 106-9.Palade, G. and Palay, S. L. (1954). Electron microscope observations of interneuronal and neuromuscular synapses. Anatomical Record 118, 335-336.Palay, S. L. and Palade, G. E. (1955). The fine structure of neurons. J Biophys Biochem Cytol 1, 69-88.Ramon y Cajal, S. (1906). The structure and connexions of neurons. Amsterdam: Elsevier Publishing Company 1967.Ramón y Cajal, S. (1909-1911). Histologie du système nerveux de l'homme et des vertébrés. Paris: A. Maloine.Ramón y Cajal, S. (1995). Histology of the Nervous System. New York: Oxford University Press.Rydqvist, B., Lin, J. H., Sand, P. and Swerup, C. (2007). Mechanotransduction and the crayfish stretch receptor. Physiol Behav 92, 21-8.Wine, J. (1984). The structural basis of an innate behavioural pattern. Journal of Experimental Biology 112, 283-319.Young, J. Z. (1936). The structure of nerve fibers in cephalapods and crustacea. Proceedings of the Royal Society of London (B) Biological Sciences121, 319-337.Young, J. Z. (1938). The functioning of the giant nerve fibres of the squid. Journal of Experimental Biology 15, 170-185.