Skip to main content
Ir a la página de inicio de la Comisión Europea (se abrirá en una nueva ventana)
español es
CORDIS - Resultados de investigaciones de la UE
CORDIS

Selective vulnerability of neuronal degeneration in Parkinson’s disease: the load of routine behaviour

Objetivo

Parkinson’s disease (PD) is characterized by striatal dopamine (DA) depletion due to loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc).Understanding the mechanisms underlying the onset and progression of SNpc damage is a primary unmet goal in PD research.Cell loss occurs earliest and foremost in the ventro-lateral region of the SNpc.Previous work defines anatomical factors determining the vulnerability of the ventro-lateral SNpc:their large axonal arborisations,bursting activity with high Ca++ inflow,high oxidative stress and sensitivity to aging.However all of these features are shared by SNpc neurons but neurodegeneration in PD begins specifically by the ventro-lateral tier. This DA depletion first occurs in the posterior striatum, which is involved and required for habit formation and routine behaviour.Indeed the earliest motor features of PD are commonly associated with impairment of automatic movements.The striatum is well known to be engaged in learning and habit formation,a process that is DA dependent.Striatal DA is released phasically (SNpc firing related) triggered by emotional responses,whereas tonic dopaminergic modulation (non-SNpc firing related),predominates in routine behaviour. The precise mechanism whereby DA regulates the learning of a routine is not well defined but SNpc dopaminergic neurons are engaged in behavioural tasks showing an activation of their firing rate at the start of an instrumental task. This provides support to the notion that DA signals the onset/offset of a task and perhaps switching between tasks.In addition, they have a higher response to external stimuli (alertness, sensory) and to emotional behaviours (i.e. reward, salience). It is hypothesized here that in order to control the whole spectrum of a task, from goal directed to habitual, the ventro-lateral SNpc neurons are under higher functional demand, and the consequent metabolic overload makes them more susceptible to degeneration.

Ámbito científico (EuroSciVoc)

Programa(s)

Tema(s)

Régimen de financiación

MSCA-IF-EF-RI - RI – Reintegration panel

Ver todos los proyectos financiados en el marco de este régimen de financiación

Convocatoria de propuestas

(se abrirá en una nueva ventana) H2020-MSCA-IF-2014

Ver todos los proyectos financiados en el marco de esta convocatoria

Coordinador

FUNDACION INVESTIGATION HM HOSPITALES
Aportación neta de la UEn
€ 170 121,60
Dirección
PLAZA DEL CONDE DE VALLE SUCHIL, N 2, PLANTA 1
28015 Madrid
España
Región
Comunidad de Madrid Comunidad de Madrid Madrid
Tipo de actividad
Research Organisations
Enlaces
Coste total
€ 170 121,60