Download Are `volume dials` in the spinal cord involved in Motor Neuron

Are ‘volume dials’ in the spinal cord involved in Motor Neuron Disease?
Lissa Herron and Gareth Miles, School of Biology, University of St Andrews
What goes wrong in MND?
Introduction:
‘Volume dial’ synapse on motor neurons
Upper Motoneurons
Motor Neuron Disease (MND) is a fatal neurodegenerative disease with which more than 130 people are
newly diagnosed in Scotland each year. MND damages
and kills neurons in the spinal cord called motor neurons
which send signals directly to muscles to make them
contract. Loss of motor neurons therefore leads to
paralysis and death within 3-4 years of diagnosis. There is
neither a cure nor any effective treatments for MND.
Brain
(From interneuron)
C-bouton
Spinal cord
We are therefore trying to learn more about the disease so
that new treatment strategies can be designed. We are
specifically interested in the potential involvement of other
neurons in the spinal cord called interneurons which form
direct connections (synapses) with motor neurons.
Motoneuron
?
Spinal interneurons
Lower Motoneurons
M2-type Acetylcholine
Receptor
We are currently investigating the potential role of a group
of interneurons and their synapses on motoneurons
(called C-boutons) which we have recently discovered act
like a ‘volume dial’ to control the strength of the signals
that motor neurons send to muscles.
Muscles
Acetylcholine (neurotransmitter)
Vesicular Acetylcholine
Transporter (VAChT)
Labelling and measuring ‘volume dial’ synapses on motor neurons in MND mice
ChAT (Motor Neurons)
VAChT (C-boutons)
ChAT/VAChT
Number of C-boutons per 100µM
of motor neuron perimeter
Average size of C-boutons on
motor neurons
12
(n/100µm)
3
9
*
6
2
MN
3
.
0
0
3
3
We use a technique (immunohistochemistry) involving antibodies which bind to
specific proteins of interest to label motor neurons and C-boutons in preserved
(fixed) spinal cord tissue obtained from MND mice. Because the antibodies have
fluorescent molecules attached to them we can use a laser microscope (confocal)
to visualise motor neurons (MN) and C-boutons (arrowhead).
1
MND
mouse
Normal
mouse
0
3
MND
mouse
Normal
mouse
Graphs above show our analysis of C-boutons on motor
neurons from MND and normal mice. The number of Cboutons does not change in MND mice when corrected for
cell size but the C-boutons are on average larger in MND
mice. ( indicates significant difference)
*
2+
Ca -dependent K
channel
+
Summary:
The number of C-bouton synapses on motor
neurons is unchanged in MND mice when corrected
for the fact that surviving motoneurons are smaller in
symptomatic MND mice.
C-boutons are larger in MND mice - perhaps
reflecting an attempt to compensate for reduced motor
neuron output by turning up this ‘volume dial’ synapse.
(µm)
3
+
Kv2.1 K Channel
Who are we?
Dr Lissa Herron
Post doctoral researcher working in the Neural Control
of Movement lab, Biology, University of St Andrews
Dr Gareth Miles
Lecturer & Head of the Neural Control of Movement lab
An investigation of cholinergic synapses on motoneurons in Amyotrophic Lateral Sclerosis (ALS): a 'synaptic stripping' hypothesis for ALS
Lissa Herron and Gareth B. Miles, School of Biology, University of St Andrews