Nature Reviews Neuroscience

doi: 10.1038/nrn2944pmid: N/A

Welberg, Leonie

doi: 10.1038/nrn2937pmid: 20979317

Regional variations in aerobic glycolysis in young adults correlate spatially with amyloid-β deposition in older individuals.

Danovi, Safia Ali

doi: 10.1038/nrn2934pmid: 20979318

DISC1 negatively regulates synaptic strength by inhibiting the TNIK-dependent stabilization of postsynaptic proteins.

doi: 10.1038/nrn2942pmid: N/A

Walker, Debbie

doi: 10.1038/nrn2933pmid: 20979320

EGFR–Notch 1 pathway interactions balance neural stem cell and progenitor cell populations.

Lewis, Sian

doi: 10.1038/nrn2941pmid: 20979321

SSRIs are used to treat depression and have a delayed onset of action. The mechanism involves post-transcriptional regulation of a serotonin transporter in the raphe nucleus and the locus coeruleus.

Kingwell, Katie

doi: 10.1038/nrn2932pmid: 20979319

Glutamate can facilitate inhibitory glycine receptor signalling in the spinal cord and brainstem through allosteric modulation.

Welberg, Leonie

doi: 10.1038/nrn2940pmid: 20979323

Hedgehog signalling establishes spatial correspondence between olfactory receptor neurons and their targets in the brain through a two-step mechanism.

doi: 10.1038/nrn2943pmid: N/A

Redgrave, Peter; Rodriguez, Manuel; Smith, Yoland; Rodriguez-Oroz, Maria C.; Lehericy, Stephane; Bergman, Hagai; Agid, Yves; DeLong, Mahlon R.; Obeso, Jose A.

doi: 10.1038/nrn2915pmid: 20944662

The basal ganglia are one of the fundamental processing units of the mammalian brain. Progressive degeneration of one of their major components, the ascending dopamine projection to the striatum, is a central pathological feature of Parkinson's disease. Imaging and post-mortem investigations reveal that degeneration of the dopamine projection is uneven in most cases, with input to caudolateral sectors of the putamen most severely affected. In the animal learning literature an important distinction has been forged between goal-directed and habitual control of behaviour. When behaviour is goal-directed, action selection is determined by the relative utility of predicted outcomes, whereas habits are under stimulus control and largely independent of outcome value. A seminal series of investigations in rodents by Balleine and colleagues established that the dorsomedial associative territories of the striatum are crucial for goal-directed control, whereas laterally located sensorimotor territories are essential for habits. Formal behavioural tests (for example, outcome devaluation) were used to determine whether an observed behaviour (for example, pressing a lever) was under goal-directed or habitual control. Recent neuroimaging studies using the same formal tests suggest that a similar spatial segregation of goal-directed and habitual control is present within the human striatum. As the loss of dopamine in Parkinson's disease is predominantly from the caudolateral sensorimotor territories, we would expect patients to experience major deficits in their production of habits. Because the same behavioural output can be directed by processing in spatially segregated regions of the basal ganglia, it must be assumed that the efferent projections of goal-directed and habitual control circuits must at some point converge on the 'final common motor path'. Given that the loss of dopamine in the basal ganglia is associated with enhanced oscillatory and inhibitory outputs, we suggest that for goal-directed control to be expressed, the distorting inhibitory signals from the habit system must be overcome at the point where the goal-directed and habitual control circuits converge. We conclude by reviewing evidence suggesting that many of the behavioural difficulties experienced by patients with Parkinson's disease can be interpreted in terms of an impaired automatic control of normal habits, coupled with distorting inhibitory influences imposed on the expression of residual goal-directed behaviours. In the light of this analysis, future work will need to establish how far the reported cognitive deficits in Parkinson's disease are due to the primary disease state (additional loss of dopamine from goal-directed circuits) or are a result of goal-directed control being overwhelmed by the absence of automatic control routines that are normally provided by the stimulus–response habit systems.