an integrated view
DESCRIPTION
An Integrated view. Nerve Muscle and Movement. Assessment. SA Q totalling 70 Specimen paper http://biolpc22.york.ac.uk/404 Practical worth 30 marks, deadline 18 Dec Submit 1 practical report. To join together…. Nerve conduction Synaptic physiology Muscle contraction Mechanics of Motion - PowerPoint PPT PresentationTRANSCRIPT
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An Integrated view
Nerve Muscle and Movement
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Assessment SA Q totalling 70 Specimen paper
http://biolpc22.york.ac.uk/404
Practical worth 30 marks, deadline 18 Dec Submit 1 practical report
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To join together…Nerve conductionSynaptic physiologyMuscle contractionMechanics of MotionAxon guidance
what could be better than ……fly jumping?
with a little help from our genetics friends
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Aim How a fly is built to get away
Key reference Allen, MJ et al (2006) Making an
escape: Development and function of the Drosophila giant fibre system Sem Cell & Devel Biol. 17: 31-41
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Genetic tools EMS-induced
mutations Sequenced genome UAS GAL4 system
tissue specific knockouts
tissue specific GFP tissue may be a
few cells
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How does a fly jump?
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Jump using middle leg
Trimarchi & Schneiderman
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How far do they go?
Wild type flies go 30 mm
1 2 3 4 5 6 7
CS female fly #
0
10
20
30
ma
x d
ista
nce
jum
pe
d (m
m)
me
an
± S
E
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How much work/force? Work
KE = ½ m g d = ½ 10-6 x 10 x 0.03 = 150 nJ
Power output = 40 µW or 300 W / kg at the top end of insect muscle output
Force measure contraction isometrically peak force 25 x weight of fly
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Which muscles? zap head and record muscle potentials
here given one small and one large stimulus
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Summary thoracic muscles, very energetically
demanding
Now onto: what neuromuscular systems does the fly use?(What’s in a fly???)
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TDT
VNCCNS
tc
femurtibia
tarsus
foregut
GDN
mn
IFM
What’s in a fly?
tc - trochantermn - motor neuron GDN - Giant descending neuron [= GF] IFM – Indirect flight musclesTDT – tergal depressor of the trochanter [= TTM]VNC - ventral nerve cord
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What's in the fly CNS ?
brain
thoracic ganglion
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Plan start with
muscle motoneuron giant descending interneuron sensory input
development
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TDT muscle
Koenig & Ikeda, 2005
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this end pulls • the leg straight
this end pulls • the wing, • thorax, • stretching the IFMs
TDT has a double whammy
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TDT in section
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TDT is… Striated muscle Tubular muscle Fast twitch
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Innervation
innervated by 3 motoneurons
1 large – very extensive endings
2 small
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Neuromodulation by octopamine –
containing neuron
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TDT motoneuron thoracic
nervous system
lateral cell body
dorsal neuropil
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Summary thoracic muscles, very energetically
demanding muscle and motoneuron designed for
speed
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PSI Relay between GDN and
? drives 5 DLM
motoneurons failure occurs
separately
Amplifier ?
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GDN (=GF) GDN PSI
TDTmn
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GDN → TDTmn synapse electrical ↑ chemical ▼
ACh
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GDN → TDTmn synapse shakingB2
no electrical synapses an innexin mutant asymmetry in
innexins
shakingB2 and chats2 neither electrical nor
cholinergic synapses
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Axonal conduction in GDN AP with para Na+ channels and K
channels identified shaker potassium channels differentiate sh from slo
sh – voltage activated K channel slo - Ca activated K channel
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Excitation of GDN Visual
zap head
flash light
+benzaldehyde
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Fly eye
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Visual input to GDN Cobalt fill of GDN in Muscalobular cells
probably electricallycoupled to GDN
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Mechanosensory input
GDN (PDB segment)
antennal endings
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Summary thoracic muscles, very energetically
demanding muscle and motoneuron designed for
speed GDN circuit designed for speed and
robustness
Now onto: how does the circuit grow?
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Development GDN & TDTmn
born during embryogenesis
Connect during pupation
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Key steps GDN neurite outgrowth Axon pathfinding (larval stages—24 h
APF) Target recognition and initial synapse
formation (24–55 h APF) meet TDTmn bend
Synapse stabilization and maintenance (55–100 h APF)
So what are the Molecular regulators of growth
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bendless
Giant axon stops and does not bend
Part of ubiqutination system for degrading proteins
This degrades signal saying “go”
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Semaphorin-1a Regulates neurite
outgrowth No sema-1a GDN
axon goes to retina (50%)
Regulates bend No sema-1a GDN
axon does not bend (50%)
May be the protein bendless degrades
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Target of sema-1a Plexins ?
Which signal via Rac, a GTPase
rac blocked
Too much rac
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Summary thoracic muscles, very energetically
demanding muscle and motoneuron designed for
speed GDN circuit designed for speed and
robustness Identification of signalling molecules
controlling neuronal growth & synapses
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Habituation of jump response
dunce (phosphodiesterase) & rutabaga (adenyl cyclase)
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Jumping as a test for disease
Epilepsy
+/+
easprior
afterbang
eas
Mutants hyperexcitable followed by paralysis
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Flies as genetic models Parkinsonism, Alzheimer, Fragile X…
Behaviour, anatomy, physiology, cell biology well known
Screen for modifiers
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Summary thoracic muscles, very energetically
demanding muscle and motoneuron designed for
speed GDN circuit designed for speed and
robustness Identification of signalling molecules
controlling neuronal growth & synapses System for physiological mutant
analysis