<s>
Low-threshold	B-Algorithm
spikes	I-Algorithm
(	O
LTS	O
)	O
refer	O
to	O
membrane	O
depolarizations	O
by	O
the	O
T-type	O
calcium	O
channel	O
.	O
</s>
<s>
LTS	O
result	O
in	O
the	O
neuron	O
reaching	O
the	O
threshold	O
for	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
spike	B-Algorithm
is	O
typically	O
crowned	O
by	O
a	O
burst	B-Algorithm
of	O
two	O
to	O
seven	O
action	B-Algorithm
potentials	I-Algorithm
,	O
which	O
is	O
known	O
as	O
a	O
low-threshold	O
burst	B-Algorithm
.	O
</s>
<s>
The	O
current	O
is	O
activated	O
at	O
around	O
−60mV	O
,	O
making	O
it	O
able	O
to	O
generate	O
a	O
low-threshold	O
spike	B-Algorithm
at	O
or	O
near	O
the	O
resting	O
potential	O
.	O
</s>
<s>
As	O
a	O
result	O
,	O
one	O
or	O
more	O
short	O
bursts	O
of	O
spikes	B-Algorithm
occur	O
,	O
followed	O
by	O
hyperpolarization	O
,	O
and	O
then	O
repolarization	O
before	O
the	O
next	O
burst	B-Algorithm
.	O
</s>
<s>
examined	O
the	O
kinetics	O
behind	O
low-threshold	B-Algorithm
spikes	I-Algorithm
to	O
better	O
understand	O
their	O
significance	O
towards	O
normal	O
functions	O
of	O
the	O
brain	O
.	O
</s>
<s>
It	O
has	O
been	O
determined	O
experimentally	O
that	O
four	O
ionic	O
currents	O
contribute	O
to	O
low-threshold	B-Algorithm
spikes	I-Algorithm
,	O
generating	O
three	O
distinct	O
phases	O
after	O
hyperpolarization	O
.	O
</s>
<s>
Transient	O
outward	O
K+	O
currents	O
following	O
action	B-Algorithm
potentials	I-Algorithm
can	O
cause	O
hyperpolarization	O
,	O
allowing	O
for	O
low-threshold	B-Algorithm
spikes	I-Algorithm
.	O
</s>
<s>
Due	O
to	O
their	O
activation	O
near	O
the	O
resting	O
membrane	O
potential	O
,	O
as	O
well	O
as	O
their	O
fast	O
recovery	O
from	O
inactivation	O
,	O
they	O
are	O
able	O
to	O
generate	O
low-threshold	B-Algorithm
spikes	I-Algorithm
,	O
which	O
results	O
in	O
a	O
burst	B-Algorithm
of	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
T-type	O
channels	O
play	O
a	O
secondary	O
pacemaker	O
role	O
in	O
neurons	O
that	O
have	O
resting	O
membrane	O
potential	O
between	O
-90	O
and	O
-70	O
mV	O
as	O
they	O
have	O
an	O
important	O
role	O
in	O
the	O
genesis	O
of	O
burst	B-Algorithm
firing	I-Algorithm
.	O
</s>
<s>
The	O
LTS	O
triggers	O
Na+	O
-dependent	O
action	B-Algorithm
potentials	I-Algorithm
and	O
activates	O
high-voltage	O
activated	O
calcium	O
channels	O
.	O
</s>
<s>
Low-threshold	O
calcium	O
spikes	B-Algorithm
have	O
been	O
described	O
in	O
neurons	O
from	O
a	O
variety	O
of	O
brain	O
nuclei	O
,	O
including	O
the	O
thalamic	O
relay	O
,	O
medial	O
pontine	O
reticular	O
formation	O
,	O
lateral	O
habenula	O
,	O
septum	O
,	O
deep	O
cerebellar	O
nuclei	O
,	O
CA1-CA3	O
of	O
the	O
hippocampus	O
,	O
association	O
cortex	O
,	O
paraventricular	O
and	O
preoptic	O
nuclei	O
of	O
the	O
hypothalamus	O
,	O
dorsal	O
raphe	O
,	O
globus	O
pallidus	O
,	O
striatum	O
,	O
and	O
subthalamic	O
nucleus	O
.	O
</s>
<s>
This	O
leads	O
to	O
tonic	O
firing	O
of	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
The	O
second	O
response	O
is	O
a	O
burst	B-Algorithm
mode	O
,	O
in	O
which	O
the	O
cell	O
is	O
hyperpolarized	O
and	O
typically	O
responds	O
with	O
LTS	O
and	O
their	O
associated	O
bursts	O
of	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
There	O
is	O
a	O
strong	O
correlation	O
between	O
LTS	O
amplitude	B-Application
and	O
the	O
number	O
of	O
action	B-Algorithm
potentials	I-Algorithm
that	O
result	O
from	O
a	O
LTS	O
.	O
</s>
<s>
The	O
activation	O
of	O
either	O
metabotropic	O
glutamate	O
or	O
muscarinic	O
receptors	O
results	O
in	O
a	O
hyperpolarizing	O
shift	O
in	O
the	O
relationship	O
between	O
LTS	O
amplitude	B-Application
and	O
the	O
initial	O
potential	O
of	O
the	O
membrane	O
.	O
</s>
<s>
This	O
affects	O
the	O
maximum	O
LTS	O
amplitude	B-Application
.	O
</s>
<s>
This	O
means	O
that	O
there	O
is	O
a	O
dependency	O
between	O
the	O
LTS	O
amplitude	B-Application
and	O
voltage	O
,	O
and	O
therefore	O
the	O
resulting	O
number	O
of	O
action	B-Algorithm
potentials	I-Algorithm
generated	O
.	O
</s>
<s>
This	O
results	O
in	O
the	O
membrane	O
polarization	O
not	O
being	O
in	O
the	O
right	O
range	O
for	O
single	O
spikes	B-Algorithm
and	O
hence	O
"	O
bursts	O
"	O
result	O
.	O
</s>
<s>
The	O
striatum	O
,	O
a	O
nucleus	O
in	O
the	O
basal	O
ganglia	O
,	O
contains	O
low-threshold	O
spike	B-Algorithm
interneurons	O
.	O
</s>
<s>
Recent	O
research	O
has	O
also	O
been	O
conducted	O
on	O
the	O
T-type	O
calcium	O
channel	O
and	O
how	O
modulation	O
of	O
these	O
channels	O
may	O
allow	O
for	O
the	O
treatment	O
of	O
various	O
neurological	O
and	O
psychological	O
disorders	O
such	O
as	O
schizophrenia	B-Application
,	O
dementia	O
,	O
mania	O
,	O
and	O
epilepsy	O
.	O
</s>
<s>
T-type	O
calcium	O
channels	O
have	O
been	O
known	O
to	O
play	O
a	O
role	O
in	O
the	O
spike-and-wave	O
discharges	O
of	O
absence	O
seizures	O
.	O
</s>
<s>
The	O
amplitude	B-Application
of	O
LTS	O
has	O
been	O
shown	O
to	O
directly	O
correlate	O
with	O
the	O
size	O
of	O
the	O
transient	O
Ca2+	O
current	O
that	O
underlies	O
the	O
LTS	O
in	O
certain	O
neuronal	O
cells	O
.	O
</s>
<s>
The	O
amplitude	B-Application
of	O
the	O
Ca2+	O
spike	B-Algorithm
is	O
therefore	O
predominantly	O
dependent	O
on	O
the	O
level	O
of	O
preceding	O
membrane	O
hyperpolarization	O
and	O
the	O
depolarizing	O
input	O
.	O
</s>
<s>
As	O
with	O
the	O
action	B-Algorithm
potentials	I-Algorithm
that	O
follow	O
them	O
,	O
LTS	O
vary	O
little	O
in	O
amplitude	B-Application
or	O
shape	O
at	O
different	O
holding	O
potentials	O
.	O
</s>
<s>
This	O
dictates	O
that	O
suprathreshold	O
depolarizing	O
inputs	O
do	O
not	O
affect	O
the	O
amplitude	B-Application
and	O
only	O
factor	O
into	O
the	O
initial	O
activation	O
of	O
the	O
LTS	O
.	O
</s>
<s>
The	O
amount	O
of	O
de-inactivation	O
determines	O
the	O
conductance	O
of	O
Ca2+	O
channels	O
and	O
is	O
the	O
main	O
factor	O
that	O
contributes	O
to	O
the	O
amplitude	B-Application
of	O
LTS	O
.	O
</s>
<s>
It	O
has	O
also	O
been	O
suggested	O
that	O
the	O
activity	O
of	O
delayed	O
rectifier	O
K+	O
channels	O
can	O
affect	O
the	O
amplitude	B-Application
of	O
LTS	O
.	O
</s>
<s>
Burst	B-Algorithm
firing	I-Algorithm
caused	O
by	O
LTS	O
are	O
therefore	O
thought	O
to	O
be	O
used	O
as	O
on/off	O
signaling	O
as	O
opposed	O
to	O
tonic	O
firing	O
which	O
is	O
graded	O
and	O
more	O
responsive	O
to	O
the	O
intensity	O
of	O
depolarizing	O
inputs	O
.	O
</s>
<s>
It	O
has	O
been	O
shown	O
that	O
unlike	O
amplitude	B-Application
,	O
it	O
is	O
directly	O
affected	O
by	O
the	O
size	O
of	O
the	O
initial	O
depolarizing	O
current	O
.	O
</s>
<s>
This	O
more	O
quickly	O
activates	O
the	O
exponential	O
growth	O
of	O
the	O
Ca2+	O
spike	B-Algorithm
.	O
</s>
<s>
This	O
has	O
led	O
to	O
the	O
hypothesis	O
that	O
burst	B-Algorithm
signaling	O
as	O
a	O
result	O
of	O
LTS	O
with	O
stronger	O
activating	O
inputs	O
is	O
more	O
stable	O
than	O
LTS	O
due	O
to	O
near-threshold	O
activating	O
inputs	O
.	O
</s>
<s>
Therefore	O
,	O
much	O
research	O
has	O
been	O
conducted	O
on	O
low-threshold	B-Algorithm
spikes	I-Algorithm
in	O
the	O
neurons	O
in	O
the	O
thalamus	O
and	O
how	O
it	O
could	O
relate	O
to	O
Parkinson	O
's	O
disease	O
and	O
the	O
corresponding	O
loss	O
of	O
motor	O
function	O
.	O
</s>
<s>
Abnormal	O
LTS	O
bursting	B-Algorithm
activities	O
that	O
have	O
been	O
noted	O
in	O
awake	O
parkinsonian	O
patients	O
suggests	O
a	O
relation	O
between	O
the	O
clinical	O
condition	O
and	O
this	O
neuronal	O
activity	O
.	O
</s>
