<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
the	O
classical	O
and	O
original	O
electrophysiological	B-Application
example	O
of	O
endocannabinoid	O
function	O
in	O
the	O
central	O
nervous	O
system	O
.	O
</s>
<s>
Prior	O
to	O
the	O
demonstration	O
that	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
was	O
dependent	O
on	O
the	O
cannabinoid	O
CB1	O
receptor	O
function	O
,	O
there	O
was	O
no	O
way	O
of	O
producing	O
an	O
in	O
vitro	O
endocannabinoid	O
mediated	O
effect	O
.	O
</s>
<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
classically	O
produced	O
in	O
a	O
brain	O
slice	O
experiment	O
(	O
i.e.	O
</s>
<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
was	O
discovered	O
in	O
1992	O
by	O
Vincent	O
et	O
al.	O
,	O
(	O
1992	O
)	O
working	O
in	O
purkinje	O
cells	O
of	O
the	O
cerebellum	O
then	O
confirmed	O
in	O
the	O
hippocampus	O
by	O
Pitler	O
&	O
Alger	O
,	O
1992	O
.	O
</s>
<s>
This	O
build-up	O
of	O
negative	O
charge	O
from	O
the	O
chloride	O
ions	O
results	O
in	O
the	O
hyperpolarization	O
of	O
the	O
target	O
cell	O
,	O
making	O
it	O
less	O
likely	O
to	O
fire	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
In	O
their	O
experiments	O
with	O
projection	O
neurons	O
in	O
the	O
hippocampus	O
and	O
cerebellum	O
,	O
both	O
groups	O
noticed	O
that	O
a	O
train	O
of	O
action	B-Algorithm
potentials	I-Algorithm
in	O
these	O
cells	O
resulted	O
in	O
a	O
temporary	O
reduction	O
in	O
inhibitory	O
currents	O
caused	O
by	O
GABA-ergic	O
interneurons	O
.	O
</s>
<s>
Since	O
this	O
reduction	O
of	O
inhibitory	O
currents	O
could	O
be	O
invoked	O
simply	O
by	O
depolarization	O
of	O
the	O
target	O
cell	O
,	O
this	O
phenomenon	O
was	O
termed	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
.	O
</s>
<s>
While	O
initially	O
discovered	O
in	O
CA1	O
neurons	O
of	O
the	O
hippocampus	O
and	O
Purkinje	O
cells	O
in	O
the	O
cerebellum	O
,	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
a	O
pretty	O
ubiquitous	O
phenomenon	O
and	O
has	O
been	O
demonstrated	O
in	O
other	O
areas	O
of	O
the	O
brain	O
such	O
as	O
the	O
basal	O
ganglia	O
,	O
the	O
cortex	O
,	O
the	O
amygdala	O
,	O
and	O
the	O
hypothalamus	O
(	O
Katona	O
et	O
al	O
.	O
</s>
<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
was	O
thought	O
to	O
be	O
due	O
to	O
a	O
reduction	O
in	O
presynaptic	O
neurotransmitter	O
release	O
for	O
2	O
reasons	O
:	O
</s>
<s>
These	O
observations	O
suggested	O
that	O
no	O
changes	O
occurred	O
in	O
the	O
post-synaptic	O
cell	O
to	O
change	O
its	O
responsiveness	O
to	O
GABA	O
during	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
.	O
</s>
<s>
Somehow	O
,	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
appeared	O
to	O
be	O
mediated	O
by	O
a	O
retrograde	O
synaptic	O
messenger	O
whose	O
synthesis	O
or	O
release	O
was	O
stimulated	O
by	O
the	O
depolarization	O
of	O
the	O
target	O
cell	O
.	O
</s>
<s>
The	O
chemical	O
messengers	O
presumed	O
to	O
be	O
responsible	O
for	O
mediating	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
was	O
discovered	O
by	O
three	O
separate	O
groups	O
in	O
2001	O
.	O
</s>
<s>
All	O
three	O
demonstrated	O
heavy	O
involvement	O
of	O
the	O
CB1	O
cannabinoid	O
receptor	O
in	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
,	O
suggesting	O
that	O
the	O
endocannabinoids	O
were	O
the	O
brain	O
's	O
mediators	O
of	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
.	O
</s>
<s>
They	O
showed	O
that	O
cannabinoid	O
receptor	O
agonists	O
,	O
drugs	O
that	O
mimic	O
the	O
actions	O
of	O
endocannabinoids	O
or	O
THC	O
,	O
could	O
evoke	O
the	O
same	O
reduction	O
in	O
inhibitory	O
currents	O
caused	O
by	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
.	O
</s>
<s>
They	O
also	O
demonstrated	O
that	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
could	O
be	O
prevented	O
by	O
cannabinoid	O
receptor	O
antagonists	O
,	O
drugs	O
that	O
block	O
the	O
actions	O
of	O
cannabinoid	O
compounds	O
.	O
</s>
<s>
Other	O
lines	O
of	O
evidence	O
support	O
the	O
role	O
of	O
the	O
CB1	O
receptor	O
in	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
.	O
</s>
<s>
This	O
receptor	O
is	O
distributed	O
very	O
widely	O
throughout	O
the	O
brain	O
,	O
covering	O
all	O
areas	O
where	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
has	O
been	O
observed	O
(	O
Herkenham	O
et	O
al	O
.	O
</s>
<s>
The	O
CB1	O
receptor	O
also	O
appears	O
to	O
be	O
expressed	O
mainly	O
on	O
GABA-ergic	O
pre-synaptic	O
terminals	O
,	O
making	O
it	O
an	O
excellent	O
candidate	O
for	O
mediating	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
(	O
Matyas	O
et	O
al	O
.	O
</s>
<s>
Lastly	O
,	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
research	O
was	O
finally	O
applied	O
to	O
mice	O
that	O
had	O
the	O
CB1	O
receptor	O
genetically	O
"	O
knocked-out	O
"	O
.	O
</s>
<s>
The	O
discovery	O
that	O
depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
mediated	O
by	O
endocannabinoids	O
finally	O
explained	O
why	O
both	O
the	O
CB1	O
receptor	O
and	O
the	O
endocannabinoids	O
are	O
both	O
so	O
widely	O
distributed	O
in	O
the	O
brain	O
.	O
</s>
<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
a	O
very	O
common	O
form	O
of	O
short-term	O
plasticity	O
and	O
thus	O
needs	O
to	O
be	O
mediated	O
by	O
a	O
commonly	O
found	O
neurotransmitter	O
.	O
</s>
<s>
Depolarization-induced	B-Algorithm
suppression	I-Algorithm
of	I-Algorithm
inhibition	I-Algorithm
is	O
therefore	O
the	O
primary	O
cortical	O
process	O
mediated	O
by	O
the	O
endocannabinoids	O
,	O
and	O
may	O
contribute	O
to	O
many	O
forms	O
of	O
cortical	O
plasticity	O
and	O
synaptic	O
strengthening	O
,	O
such	O
as	O
in	O
long-term	O
potentiation	O
(	O
Carlson	O
et	O
al	O
.	O
</s>
