The striatum — the primary input nucleus of the basal ganglia — is composed of which two structures?

A: Globus pallidus and substantia nigra

B: Caudate nucleus and putamen

C: Subthalamic nucleus and globus pallidus externa

D: Nucleus accumbens and substantia nigra pars reticulata

The striatum — from the Latin stria, referring to its striated appearance caused by white matter fibres crossing it — is the main input structure of the basal ganglia. It is composed of the caudate nucleus (a curved structure following the lateral ventricles) and the putamen (more lateral, adjacent to the insula). Together they receive the majority of cortical input to the basal ganglia. The nucleus accumbens, while sometimes included as ventral striatum, is part of the limbic/reward circuitry. The entire system projects onwards through the globus pallidus to the thalamus and back to the cortex.

In the direct pathway of the basal ganglia, how does activity in the striatum affect thalamic output to the cortex?

A: Striatal activation inhibits the globus pallidus interna (GPi), disinhibiting the thalamus, which then excites the cortex

B: Striatal activation directly excites the thalamus without involving the globus pallidus

C: Striatal activation inhibits the thalamus directly, reducing cortical motor output

D: Striatal activation excites the subthalamic nucleus, which then excites the cortex

The direct pathway follows the sequence: Cortex → Striatum (D1 neurons) → GPi/SNr (inhibited) → Thalamus (disinhibited) → Cortex. Because GABAergic striatal neurons inhibit the tonically active GPi, which in turn tonically inhibits the thalamus, striatal activation removes this double inhibition — releasing the thalamus to excite the cortex and facilitate movement. This is the "go" pathway: dopamine acting on D1 receptors in the striatum strengthens the direct pathway, promoting movement initiation.

In the indirect pathway of the basal ganglia, striatal activation ultimately results in decreased thalamic activity and reduced cortical motor output, acting as a "stop" signal for competing movements.

Svar: Sant

The indirect pathway follows the sequence: Cortex → Striatum (D2 neurons) → GPe (inhibited) → Subthalamic nucleus (STN) (disinhibited) → GPi/SNr (excited) → Thalamus (inhibited) → reduced cortical excitation. Because D2 striatal neurons project to the external globus pallidus (GPe), which normally inhibits the STN, their activation removes GPe inhibition from STN, allowing STN to drive GPi activity, which then strongly inhibits the thalamus. Dopamine acting on D2 receptors weakens this pathway, favouring the direct pathway. The interplay of direct (go) and indirect (stop) pathways allows precise selection of desired movements while suppressing competing ones.

The substantia nigra pars compacta (SNc) projects dopaminergic fibres to the striatum via the nigrostriatal pathway. What is the effect of this dopaminergic input on the direct and indirect pathways?

A: Dopamine inhibits both pathways equally, reducing overall basal ganglia output

B: Dopamine activates D1 receptors to strengthen the direct (go) pathway and activates D2 receptors to weaken the indirect (stop) pathway — together promoting movement

C: Dopamine selectively strengthens the indirect pathway only, acting as a brake on movement initiation

D: Dopamine acts exclusively on the subthalamic nucleus, bypassing the striatum

Dopamine from the SNc has complementary effects that together promote movement initiation. D1 receptors are expressed primarily on direct pathway neurons: dopamine acts on these to strengthen the direct (go) pathway. D2 receptors are expressed primarily on indirect pathway neurons: dopamine acts on these to weaken the indirect (stop) pathway. The net effect of dopamine release is to facilitate selected movements and suppress competing ones. In Parkinson's disease, progressive loss of SNc neurons reduces striatal dopamine, weakening the direct pathway and strengthening the indirect pathway — producing the movement poverty (bradykinesia, rigidity) that characterises the condition.

Parkinson's disease is characterised by which of the following sets of motor symptoms, caused by dopaminergic loss in the substantia nigra pars compacta?

A: Chorea (involuntary jerky movements), hypotonia, and preserved movement speed

B: Bradykinesia (slowed movement), resting tremor, muscular rigidity, and postural instability

C: Ataxia (incoordination), wide-based gait, and intention tremor

D: Hemiplegia, spasticity, and hyperreflexia

Parkinson's disease is caused by the selective degeneration of dopaminergic neurons in the SNc, with accompanying Lewy body (alpha-synuclein) pathology. Without normal dopaminergic input, the indirect pathway is overactive and the direct pathway is underactive, resulting in increased GPi inhibition of the thalamus and reduced cortical facilitation of movement. The four cardinal features are bradykinesia (slowness of movement, the most diagnostically essential feature), resting tremor (typically 4–6 Hz "pill-rolling"), rigidity (cogwheel or lead-pipe resistance to passive movement), and postural instability. Ataxia (option C) is characteristic of cerebellar, not basal ganglia, disorders.

Huntington's disease causes which of the following, and through which mechanism?

A: Progressive loss of dopaminergic neurons in the SNc, producing poverty of movement

B: Selective early degeneration of striatal neurons projecting through the indirect pathway, producing chorea (involuntary, dance-like movements)

C: Loss of cerebellar Purkinje cells, producing progressive ataxia and dysarthria

D: Excitotoxic damage to the subthalamic nucleus, producing ballismus (flinging limb movements)

Huntington's disease (HD) is caused by an expanded CAG repeat in the HTT gene, producing a toxic mutant huntingtin protein. Striatal medium spiny neurons are the earliest and most selectively affected: specifically, D2-expressing indirect pathway neurons degenerate first. Loss of the indirect pathway removes the "stop" signal, producing chorea — involuntary, purposeless, dance-like movements that are the hallmark of early HD. As the disease progresses and direct pathway neurons are also lost, chorea may eventually be replaced by rigidity and akinesia, producing a Parkinson-like picture. Cognitive decline and psychiatric symptoms (depression, obsessionality, psychosis) are also common.

The basal ganglia play a critical role in habit formation and procedural learning, operating in parallel with the hippocampus, which handles declarative (fact-based) memory.

Svar: Sant

Research with amnesic patients and animal lesion studies has established a clear double dissociation: hippocampal damage impairs declarative (explicit) memory while sparing habit (procedural) learning; basal ganglia damage (particularly dorsal striatum) impairs habit and procedural learning while largely sparing declarative memory. Knowlton, Mangels, and Squire (1996) demonstrated this elegantly with the weather prediction task: amnesic patients with hippocampal damage performed normally on the probabilistic categorisation learning that depended on the basal ganglia, while patients with Parkinson's (basal ganglia damage) showed the reverse. The striatum learns stimulus-response associations through dopamine-based reinforcement, binding cues to actions over many repetitions.

Obsessive-compulsive disorder (OCD) has been linked to hyperactivity in which basal ganglia-cortex loop?

A: The sensorimotor loop connecting putamen to primary motor cortex

B: The limbic loop connecting nucleus accumbens to anterior cingulate cortex

C: The orbitofrontal-caudate loop: hyperactivity in the orbitofrontal cortex drives the caudate, which fails to inhibit recurring intrusive thoughts and compulsive behaviours

D: The cognitive loop connecting mediodorsal thalamus to dorsolateral prefrontal cortex

Neuroimaging studies consistently show hyperactivity in the orbitofrontal cortex (OFC), caudate nucleus, and thalamus in OCD patients at rest and during symptom provocation. The orbitofrontal-caudate-thalamo-cortical loop is thought to malfunction: the OFC generates an "error signal" or sense of incompleteness that normally drives checking behaviour, but in OCD this loop becomes locked in a hyperactive cycle that the patient cannot voluntarily terminate. Deep brain stimulation of the anterior limb of the internal capsule (ALIC) or the subthalamic nucleus — both of which modulate this loop — can be effective treatment-resistant OCD. Serotonergic medications (SSRIs) reduce OFC-caudate hyperactivity and symptom severity.

Wolfram Schultz's recordings from dopamine neurons in the ventral tegmental area (VTA) and substantia nigra showed that dopamine neurons encode:

A: The absolute value of a reward — firing more strongly for larger rewards regardless of context

B: Reward prediction errors — firing above baseline when rewards are better than expected, returning to baseline when rewards match predictions, and falling below baseline when expected rewards are omitted

C: Punishment signals — increasing firing when the animal receives an aversive outcome

D: Movement velocity — tracking the speed of approach toward a reward rather than the reward itself

Schultz and colleagues (1997) made a landmark discovery: dopamine neurons do not simply code for reward value. Instead, they signal the difference between received and predicted reward — the reward prediction error (RPE). When an unexpected reward occurs, dopamine neurons fire a burst above baseline. When a predictive cue reliably predicts the reward, the burst shifts to the cue and the reward itself produces no response. When the expected reward is omitted, dopamine firing dips below baseline. This temporal difference learning signal is mathematically equivalent to the TD error in reinforcement learning algorithms, providing a biological substrate for model-free learning from outcomes. RPE signals propagate through the nigrostriatal and mesolimbic pathways to update striatal synaptic weights and guide future behaviour.