This document provides a literature review and experimental methods related to investigating the functional connection between the nucleus accumbens core and the ventromedial thalamus. The literature discusses the anatomical connection between these two regions and their roles in impulse control. The experimental methods describe administering muscimol, a GABA agonist, into the ventromedial thalamus of rats trained on a fixed ratio task to test if this impairs their performance, which could indicate a functional connection between the two brain regions.

1. Relevant
Research
Literature
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G.
E.,
DeLong,
M.
R.,
&
Strick,
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L.
(1986).
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UTer,
A.
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Basso,
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(2008).
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ArbuthnoT,
GW
et
al.
(1990).
DistribuFon
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Contacts
of
the
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Terminals
arising
from
Neurons
in
the
Rat
Ventromedial
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Nucleus.
Neuroscience,
38
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47-­‐60.
Buss,
A.H.,
&
Plomin,
R.
(1975).
A
temperament
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personality
development.
Wiley,
New
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R.N.,
PennicoT,
D.R.,
Sugathapala,
C.L.,
Robbins,
T.W.,
and
EveriT,
B.J.
(2001)
Impulsive
choice
induced
in
rats
by
lesions
of
the
nucleus
accumbens
core.
Science,
292:
2499-­‐
2501.
Evenden,
J.L.
(1998b).
The
pharmacology
of
impulsive
behaviour
in
rats
III:
the
effects
of
amphetamine,
haloperidol,
imipramine,
chlordiaxepoxide
and
ethanol
on
a
paced
fixed
consecuFve
number
schedule.
Psychopharmacology,
138,
295-­‐304.
Neill,
Darryl
B.,
Fenton,
Howard,
and
JusFce,
Joseph.
(2002).
Increase
in
accumbal
dopaminergic
transmission
correlates
with
response
cost
not
reward
of
hypothalamic
sFmulaFon.
Behavioural
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137,
129-­‐138
Nicholai,
Henry
and
Neill,
Darryl
(2013).
Roles
of
sub-­‐regions
of
the
Ventromedial
Nucleus
of
the
Thalamus
(VMT)
in
an
ATenFonal
task.
Honors
thesis,
Emory
University.
Paine,
T.A.,
Slipp,
L.E.,
and
Carlezon,
W.A.,
Jr.
(2011)
Schizophrenia-­‐like
aTenFonal
deficits
following
blockade
of
prefrontal
cortex
GABAA
receptors.Neuropsychopharmalogy,
36:
1703-­‐
1713.
Pezze
MA,
Dalley
JW,
Robbins
TW
(2009)
RemediaFon
of
aTenFonal
dysfuncFon
in
rats
with
lesions
of
the
medial
prefrontal
cortex
by
intra-­‐accumbens
administraFon
of
the
dopamine
D2/3
receptor
antagonist
sulpiride.
Psychopharmacology
202:307-­‐313.
Acknowledgments
The
author
would
like
to
thank
Dr.
Darryl
Neill
and
Akshay
Goswami
for
their
assistance
as
well
as
mentorship
during
the
experimental
process.
Experimental
Procedure
Adult
Sprague
Dawley
male
rats
were
placed
on
a
restricted
feeding
schedule
maintaining
them
at
90%
of
their
free-­‐feeding
weight,
prior
to
training
for
the
FR-­‐8
task.
These
rats
had
bilateral
guide
cannulae
implanted
top
terminate
1
mm
above
the
medial
VMT.
Based
on
the
effecFve
doses
in
the
previous
FCN-­‐8
study,
20
ng
muscimol
HBr
dissolved
in
isotonic
saline
vehicle,
or
the
vehicle
alone,
were
injected
into
the
VMT
in
a
volume
of
0.5
µl
prior
to
tesFng
sessions
(see
Fig.
2,
Fig.
3)
.
Test
sessions
lasted
20
min.
Conclusions
The
apparent
increase
in
“impulsive”
responding
in
the
Fixed
ConsecuFve
Number
(FCN)-­‐8
task
following
medial
VMT
injecFon
of
muscimol
may
actually
be
the
result
of
an
inability
to
maintain
responding
on
the
FCN
lever
of
this
two-­‐
lever
task.
This
experiment
showed
that,
even
when
only
one
lever
was
present,
and
8
lever-­‐presses
were
required
to
obtain
a
food
pellet
(FR-­‐8),
the
musimol
significantly
depressed
responding.
This means only the “t” in
“title” gets capitalized.
A
Study
on
Impulsive
Behavior:
Inves7ga7on
of
the
Func7onal
Connec7on
between the
Accumbens
Core
and
the
Medial
Ventral
Thalamus
U.
B.
Hoang1,
D.
B.
Neill1,2
Program
in
Neuroscience
and
Behavioral
Biology1,
Department
of
Psychology2
Emory
University,
Atlanta,
GA
30322
IntroducFon
The
ventromedial
nucleus
of
the
thalamus
(VMT)
in
rats
is
a
major
link
between
basal
ganglia
efferents
and
the
cerebral
cortex.
In
parFcular,
the
VMT
receives
GABAergic
afferents
from
the
substanFa
nigra,
pars
reFculata,
which
in
turn
receives
afferents
from
the
nucleus
accumbens
core
and
the
dorsal
striatum
via
the
“direct
path”
(see
Fig.
4
).
Although
the
medial
VMT
(mVMT)
and
the
accumbens
core
are
connected
anatomically,
evidence
is
needed
to
determine
whether
the
accumbens
core
and
the
mVMT
are
connected
in
a
funcFonal
circuitry.
Previous
work
in
the
Neill
lab
showed
that
injecFon
of
the
GABA
agonist
muscimol,
which
hyperpolarizes
neurons,
into
the
mVMT
impairs
impulse
control
in
rats
on
the
Fixed-­‐ConsecuFve
Number
(FCN-­‐8)
task,
causing:
• A
significant
decrease
in
bar
presses
on
the
FCN
lever
before
switching
to
the
Reinforcement
lever.
• An
overall
decrease
in
overall
bar-­‐pressing
• No
effect
on
the
consummatory
behavior
(subjects
would
eat
the
food
pellets
presented
in
front
of
them).
The
decrease
in
overall
bar-­‐pressing
suggests
that
there
may
be
other
factors,
more
complex
than
impulse
control,
which
impair
the
subjects’
ability
to
complete
the
task
in
order
to
receive
a
reward.
Therefore,
this
study
was
designed
to
invesFgate
if
injecFon
of
muscimol
into
the
mVMT
results
in
a
decrease
in
lever-­‐pressing
per
se.
This
was
done
by
removing
the
second
(Reward)
lever
from
the
FCN-­‐8
task;
the
rats
only
had
to
press
a
single
lever
8
Fmes
to
receive
a
food
pellet.
This
procedure
is
called
Fixed-­‐
RaFo
8
(FR-­‐8).
Hypothesis:
If
the
medial
VMT
is
responsible
for
controlling
the
subjects’
ability
to
complete
the
8
presses
of
the
FCN
lever,
muscimol
injecFons
into
the
medial
VMT
will
result
in
a
marked
decrease
in
Fixed
RaFo
8
responding.
Nigrothalamic
Projection (GABAergic)
Thalamocortical
Projections (Glutamatergic)
Substantia Nigra
Pars Reticulata
Ventromedial
Nucleus of
the Thalamus
Frontal
Cortex
Activated by nociceptive stimuli
Activated by rewarding stimuli?
Fig. 2. GABAergic projection of the
substantia nigra, pars reticulata, upon the
VMT, and the glutamatergic projection of
the VMT upon layer 1 of frontal neocortex.
FOOD
Reinforcement Lever
Reinforcement Lever
(1)
(2)
Fig.1.
Experimental
Set-­‐Up:
(1)
Fixed
ConsecuFve
Number
8:
2
levers
are
presented
in
a
test
chamber.
The
rats
are
required
to
complete
a
sequence
of
8
consecuFve
responses
on
the
FCN
lever,
before
pressing
the
the
reinforcement
lever,
to
receive
a
food
reward.
Premature
response
restarts
the
sequence.
Therefore,
impulsive
response
results
in
loss
of
a
scheduled
food
delivery
(2)
Fixed
RaFo
8:
1
lever
is
presented
in
a
test
chamber.
The
rats
are
required
to
complete
a
sequence
of
8
consecuFve
responses
on
the
FCN
lever
to
obtain
a
food
reward.
AP 6.84
AP 6.60
Fig.4. Sites of Muscimol Injections on the
VMT-M
Injection
Sites
Pre SAL Pre MUSC 10
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
PelletsReceivedonFR-8Schedule
**
Pre SAL Pre MUSC 10
0
200
400
600
800
1000
1200
LeverPressesonFR-8Schedule
**
(1) (2)
Fig.5. (1) Muscimol injection decreased the number of bar-presses, compared to performance
after saline injections (**p <.01) (2) Muscimol injection decreased the number pellets received,
compared to performance after saline injections (**p <.01) .
Results
InjecFon
of
10
ng
muscimol
soluFon
decreased
the
number
of
bar-­‐presses
and
pellets
received
compared
to
performance
following
saline
vehicle
injecFons
(**p
<.01)
Possible
RelaFonship
to
Disorders
Characterized
by
Deficits
in
“Impulse”
Control
A
number
of
psychological
disorders
include
“impulsivity”
as
part
of
their
collecFon
of
symptoms;
most
notably,
ATenFon
Deficit
HyperacFvity
Disorder
(ADHD).
These
results
suggest
that
the
neural
circuitry
involving
the
ventromedial
thalamus
and
prefrontal
cortex
may
be
involved
in
these
symptoms.
FCN Lever
Fig.3. Proposed model of the Functional Circuitry
between the Accumbens Core and the Ventral
Medial Thalamus