POSTER BIOL 499 (Uyen)
1
Relevant Research Literature Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organizaFon of funcFonally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 9, 357381. doi: 10.1146/annurev.ne.09.030186.002041 UTer, A. A., & Basso, M. A. (2008). The basal ganglia: an overview of circuits and funcFon. Neurosci Biobehav Rev, 32(3), 333342. doi: 10.1016/j.neubiorev. 2006.11.003 ArbuthnoT, GW et al. (1990). DistribuFon and SynapFc Contacts of the CorFcal Terminals arising from Neurons in the Rat Ventromedial Thalamic Nucleus. Neuroscience, 38 (1): 4760. Buss, A.H., & Plomin, R. (1975). A temperament theory of personality development. Wiley, New York. Cardinal, 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, 295304. Neill, Darryl B., Fenton, Howard, and JusFce, Joseph. (2002). Increase in accumbal dopaminergic transmission correlates with response cost not reward of hypothalamic sFmulaFon. Behavioural Brain Research: 137, 129138 Nicholai, Henry and Neill, Darryl (2013). Roles of subregions 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) Schizophrenialike 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 intraaccumbens administraFon of the dopamine D2/3 receptor antagonist sulpiride. Psychopharmacology 202:307313. 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 freefeeding weight, prior to training for the FR8 task. These rats had bilateral guide cannulae implanted top terminate 1 mm above the medial VMT. Based on the effecFve doses in the previous FCN8 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 leverpresses were required to obtain a food pellet (FR8), the musimol significantly depressed responding. A Study on Impulsive Behavior: Inves7ga7on of the Func7onal Connec7on between the Accumbens Core and the Medial Ventral Thalamus U. B. Hoang 1 , D. B. Neill 1,2 Program in Neuroscience and Behavioral Biology 1 , Department of Psychology 2 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 FixedConsecuFve Number (FCN8) task, causing: • A significant decrease in bar presses on the FCN lever before switching to the Reinforcement lever. • An overall decrease in overall barpressing • No effect on the consummatory behavior (subjects would eat the food pellets presented in front of them). The decrease in overall barpressing 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 leverpressing per se. This was done by removing the second (Reward) lever from the FCN8 task; the rats only had to press a single lever 8 Fmes to receive a food pellet. This procedure is called Fixed RaFo 8 (FR8). 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 SetUp: (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 Pellets Received on FR-8 Schedule ** Pre SAL Pre MUSC 10 0 200 400 600 800 1000 1200 Lever Presses on FR-8 Schedule ** (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 barpresses 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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Transcript of POSTER BIOL 499 (Uyen)
Relevant Research Literature
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organizaFon of
funcFonally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 9, 357-‐381. doi: 10.1146/annurev.ne.09.030186.002041
UTer, A. A., & Basso, M. A. (2008). The basal ganglia: an overview of circuits and funcFon. Neurosci Biobehav Rev, 32(3), 333-‐342. doi: 10.1016/j.neubiorev.2006.11.003
ArbuthnoT, GW et al. (1990). DistribuFon and SynapFc Contacts of the CorFcal Terminals arising from Neurons in the Rat Ventromedial Thalamic Nucleus. Neuroscience, 38 (1): 47-‐60.
Buss, A.H., & Plomin, R. (1975). A temperament theory of personality development. Wiley, New York.
Cardinal, 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 Brain Research: 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.
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
102030405060708090
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
le
**
(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
