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General introduction
a strong foundation for the hypothesis that dopamine is involved in motivated cognitive
control, they do not directly manipulate the dopamine system, nor do they provide evidence
for the involvement of any specific dopamine receptor subtype.
Box 2.1 | The striatum and its spiralling striato-nigral-striatal projections
The striatum is the input structure of the basal ganglia, a collection of nuclei located deep
in the brain, which are involved in a wide range of behaviours. The striatum can be roughly
divided into three parts: the ventral part (VS,
figure 2.1: red
), including the nucleus
accumbens, which is primarily involved in Pavlovian processes and the anticipation
of rewards, the caudate nucleus (
figure 2.1: orange/green
), which is implicated in
instrumental conditioning and goal-directed behaviour, such as the flexible updating of
task demands, and the putamen (
figure 2.1: blue
), which is involved in motor processes.
The striatum is well-connected to other parts of the brain and thus ideally suited to
integrate signals about context and novelty from the hippocampus, affective processes and
reward value from the amygdala and top-down processes such as attention, conflict and
working memory related signals from the prefrontal cortex (
figure 2.1
).
Approximately 90% of striatal neurons are GABA-ergic medium spiny neurons (MSNs),
which express dopamine receptors. Importantly, these inhibitory MSNs cannot generate
activity (unlike for example dopamine neurons). Instead, changes in striatal activity
modulate signals from other regions, such as excitatory glutamatergic inputs coming from
the frontal cortex. Dopamine signals in the striatum are thought to play an important role
in how input from other regions, such as the hippocampus and prefrontal cortex, affect
signalling in the striatum (Grace et al., 2007). These dopamine signals originate from the
midbrain (VTA/SN: ventral tegmental area and substantia nigra) and can modulate the
excitability of the striatum, either by facilitating or inhibiting neuronal activity, depending
on which dopamine receptors are stimulated (i.e. D1 or D2) and the concentration of
dopamine (
box 2.2
). Stimulation of D1 receptors increases the excitability of striatal
neurons, whereas dopamine D2 receptor stimulation decreases the responsiveness of these
neurons, making the striatum either more or less sensitive to prefrontal input, respectively
(
box 2.2
). The striatum in turn sends projections back to the cortex (via other nuclei e.g. the
pallidum, subthalamic nucleus and thalamus), forming the so-called corticostriatal circuits
(Alexander et al., 1986) and to the midbrain, forming striato-nigral-striatal loops (Haber
et al., 2000) (
figure 1.1 and 2.1
). These corticostriatal circuits are organized in functionally
specific circuits (
chapter 1
). The segregated nature of the corticostriatal circuits in
functionally specific circuits is largely maintained in these striato-nigral connections, but
importantly, each region of the striatum projects to the part of the midbrain connected to
a slightly more dorsolateral striatal region, allowing the integration of information across
circuits. This organization of the striatum and cortex in cortico-striatal-pallidal-thalamus-
cortical circuits allows them to work together to enable a broad behavioural repertoire.