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The results of the surgical treatment of AAAD are acceptable and mainly influenced by patient's status at presentation. Malperfusion of more organ systems makes the prognosis unfavourable and immediate proximal aortic repair may be sub-optimal. In these situations, alternative management strategies should be considered.

By priming brain circuits, associations between low-salience stimuli often guide future behavioral choices through a process known as mediated or inferred learning. However, the precise neurobiological mechanisms of these incidental associations are largely unknown. Using sensory preconditioning procedures, we show that type 1 cannabinoid receptors (CBR) in hippocampal GABAergic neurons are necessary and sufficient for mediated but not direct learning. Deletion and re-expression of CBR in hippocampal GABAergic neurons abolishes and rescues mediated learning, respectively. Interestingly, paired presentations of low-salience sensory cues induce a specific protein synthesis-dependent enhancement of hippocampal CBR expression and facilitate long-term synaptic plasticity at inhibitory synapses. CBR blockade or chemogenetic manipulations of hippocampal GABAergic neurons upon preconditioning affect incidental associations, as revealed by impaired mediated learning. Thus, CBR-dependent control of inhibitory hippocampal neurotransmission mediates incidental associations, allowing future associative inference, a fundamental process for everyday life, which is altered in major neuropsychiatric diseases. VIDEO ABSTRACT.

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L-DOPA is currently one of the best medications for Parkinson's disease. It was assumed for several years that its benefits and side effects were related to the enhancement of dopamine release in the dopamine-depleted striatum. The use of intracerebral microdialysis combined with a pharmacological approach has led to the discovery that serotonergic neurons are responsible for dopamine release induced by L-DOPA. The subsequent use of multisite microdialysis has further revealed that L-DOPA-stimulated dopamine release is widespread and related to the serotonergic innervation. The present Review emphasizes the functional impact of extrastriatal release of dopamine induced by L-DOPA in both the therapeutic and side effects of L-DOPA. KEYWORDS: multisite intracerebral microdialysis, L-DOPA, DA and 5-HT release, 5-HT neurons, region-dependent effects, clearance mechanisms L-DOPA is the best medication for Parkinson's disease. The use of L-DOPA as a treatment for Parkinson's disease began soon after the discovery that the striatal tissue concentration of dopamine (DA) was lower in Parkinsonian patients compared to age-matched individuals.1 The efficacy of L-DOPA was improved by combination with a peripheral inhibitor of Laromatic amino acid decarboxylase (AADC) to prevent the conversion of L-DOPA into DA in the bloodstream, thus enhancing the brain penetration of L-DOPA. Although L-DOPA is highly effective in relieving motor symptoms, numerous motor and nonmotor side-effects including L-DOPA-induced dyskinesias and psychosis can gradually emerge over time.2 The functional impact of L-DOPA in the Parkinsonian brain may not be solely restricted to its ability to restore "physiological levels" of DA in the striatum. Further investigations of its mechanism of action are thoroughly needed in order to address the motor and nonmotor side-effects of L-DOPA.Intracerebral microdialysis is a powerful sampling technique used to monitor steady-state extracellular levels of neurotransmitters in vivo. This technique has helped to decipher the mechanism of action of numerous drugs and medications with respect to their action toward neurotransmitter systems. Furthermore, the development of simultaneous implantation of multiple microdialysis probes in distinct brain regions (referred to here as multisite microdialysis) has proven its strength in revealing region-dependent dynamics of neurotransmitter release in response to pharmacological challenges and the neurochemical interactions between brain regions.Here, we summarize data showing the numerous advantages of intracerebral microdialysis to decipher the diverse features of the mechanism of action of L-DOPA in the Parkinsonian brain by using both a classical neuropharmacological approach and a multisite microdialysis approach. The present Review emphasizes the effect of L-DOPA in extrastriatal brain regions and how the region-dependent pattern of DA release induced by L-DOPA through serotonergic (5-HT) neurons may be relevant to its therapeutic and/or side-effects. I. THE US...

Highlights d Developmental deficiency in n-3 PUFA lipid species leads to motivational deficits d n-3 PUFA deficiency increases D2-MSN lateral inhibition in the nucleus accumbens d Rescue of n-3 PUFA levels in D2 neurons normalizes lateral inhibition of D2-MSNs d Rescue of PUFA levels in D2 neurons enhances motivation under n-3 PUFA deficiency

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