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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.
NigrothalamicProjection (GABAergic)
ThalamocorticalProjections (Glutamatergic)
Substantia NigraPars Reticulata
VentromedialNucleus ofthe Thalamus
FrontalCortex 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 LeverReinforcement 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 100
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100110120130140150160170180190200
Pelle
ts R
ece
ived o
n F
R-8
Sch
edule
**
Pre SAL Pre MUSC 100
200
400
600
800
1000
1200L
eve
r P
ress
es
on
FR
-8 S
che
du
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(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
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