Title:
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The role of cortico-striato-thalamo-cortical circuits of the brain in inter-temporal choice and its underlying behavioural mechanisms in the rat
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Inter-temporal choice refers to a situation where a decision has to be made between
two or more rewards of different sizes that are available after different delays. There
is evidence that abnormalities of inter-temporal choice behaviour (biased selection of
smaller immediate rewards in preference to larger delayed rewards) may be associated
with some clinical conditions, such as attention deficit hyperactivity disorder
(ADHD), which are characterised by deficient impulse control. Evidence suggests that
abnormal inter-temporal choice behaviour and occurrence of ADHD may develop
from dysfunction of cortico-striato-thalamo-cortical (CSTC) circuits in the brain.
Three experiments described in this thesis examined. the effects of a systematic
disruption of CSTC circuits on inter-temporal choice performance in rats. The results
of these experiments generated hypotheses about the roles of some components of the
CSTC circuits in regulating the efficacy or 'instantaneous valueof reinforcers, which
were tested in two further experiments that employed quantitative analyses of
performance on a single-operandum progressive ratio (PR) schedule of reinforcement.
Chapter 1 reviews the literature dealing with key theoretical concepts and
experimental findings pertaining to inter-temporal choice and single-operandum
schedules. Section 1. J is a preamble that offers a general background to the work that
was carried out as well as the aims and brief outline of the experiments that were
conducted. Section 1.2 reviews the history of the concept of inter-temporal choice and
the way it has been accounted for from economic as well as behavioural perspectives.
It examines the empirical data from the experimental analysis of behaviour in
inter-temporal choice tasks and gives an account of the putative neurobiology that
underlies this behaviour. Section 1.3 reviews the theoretical as well as practical
notions of the use of PR schedules and their potential for dissociating behavioural
mechanisms involved in inter-temporal choice behaviour.
Chapters 2~ describe a series of five experiments that examined the effects
on inter-temporal choice and PR performance following damage inflicted to the
CSTC circuits in the rat brain.
Experiment I sought to elaborate on previous findings that lesions of the core
of the nucleus accumbens (Acbe) promote preference for smaller earlier reinforcers
over larger delayed reinforcers in inter-temporal choice paradigms by clarifying
whether this reflects an effect of the lesion on the rate of delay discounting, on
sensitivity to reinforcer magnitude, or both. A quantitative method that allows effects
on delay discounting to be distinguished from effects on sensitivity to reinforcer size
showed that lesions to the Acbe promote preference for smaller, earlier reinforcers,
and suggested that this reflects an effect of the lesion on the rate of delay discounting.
Experiment II examined the effect of disconnecting the orbital prefrontal
cortex (OPFC) from the Ache on inter-temporal choice performance. Rats were given
excitotoxin-induced contralateral lesions of the OPFC and Acbe (disconnection),
severing of the anterior corpus callosum (callosotomy), a combined lesion
(disconnection+ca11osotomy) or sham lesions. Using the same behavioural training
and quantitative method as in Experiment L the disconnection+callosotomy group
showed a lower intercept of the indifference function than the sham-lesioned group;
the disconnection group showed a similar but less robust effect, whereas tbe
callosotomy group did not differ significantly from the sbam-lesioned group. The
results suggest that OPFC-AcbC connections are involved in delay discounting of
food reinforcers.
Tbe subthalamic nucleus (STN) is a major relay in the indirect striatofugal
pathway and plays an important role in extrapyramidal motor control. Recent findings
indicate that it may also play a role in modulating the efficacy of food reinforcers. The
objective of Experiment ill was to examine the effect of lesions of the STN on
inter-temporal choice performance. Following bilateral excitotoxin-induced or sham
lesions of the STN and behavioural training and methodology as Experiments I and IT,
STN-lesioned rats showed a flatter slope of the indifference function (implying higher
instantaneous reinforcer values) compared to sham-lesioned rats; there was no
difference in intercepts between the two groups. The results agree with recent findings
that indicate a function of the STN in incentive value. However, in contrast to some
previous studies, these results do not indicate a role of the STN in delay discounting.
Experiment N investigated the effect of AcbC lesions on performance on a
PR schedule using a quantitative model that discriminates between effects of
interventions on motor and motivational processes. Following bilateral
excitotoxin-induced and sham lesions of the AcbC, rats were trained to respond for
food reinforcers under a PR schedule. The motor parameter, d, was significantly
higher in the AcbC-Iesioned than the sham-Iesioned group, reflecting lower overall
response rates in the lesioned group. The motivational parameter, a, was sensitive to
changes in reinforcer magnitude, but showed no significant difference between the
two groups. The AcbC-lesioned group showed longer post-reinforcement pauses and
lower running response rates than the sham-lesioned group. The results suggest that
destruction of the Ache impairs response capacity but does not alter the efficacy of
food reinforcers. The results are consistent with the findings in Experiment I that
Ache lesions do not alter sensitivity to reinforcer size in inter-temporal choice
schedules.
The objective of Experiment V was to examine the effect of lesions of the
STN on performance on a PR schedule using the same quantitative model as in
Experiment IV. After bilateral excitotoxin-induced and sham lesions of the STN, rats
were given the same behavioural training under the same protocol as in Experiment
N . Parameter t5 was significantly higher in the STN-lesioned than the sham-lesioned
group. indicating lower overall response rates in the lesioned group. Parameter a was
significantly higher in the STN-lesioned group than in the sham-Iesioned group,
consistent with the results from Experiment ill which suggested enhanced
instantaneous reinforcer value in the STN-lesioned group compared to the
sham-lesioned group. The results suggest that destruction of the STN impairs
response capacity and enhances the incentive value of food reinforcers.
In conclusion, chapter 7 recapitulates the findings from all the experiments
that were carried out and discusses the emerging implications about the role of CSIC
circuits in regulating inter-temporal choice behaviour, and the behavioural processes
that may underline this role.
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