Limits...
Habitual behavior and dopamine cell vulnerability in Parkinson disease.

Hernández LF, Redgrave P, Obeso JA - Front Neuroanat (2015)

View Article: PubMed Central - PubMed

Affiliation: Fundacion HM, Hospital HM Puerta del Sur, Centre for Integrative Neuroscience A.C., Mostoles and CEU San Pablo University Madrid, Spain ; Center for Networked Biomedical Research on Neurodegenerative Diseases, Institute Carlos III Madrid, Spain.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

It is now well established that dopaminergic neurons in the ventro-lateral tier of the substantia nigra pars compacta (SNpc), which project mainly to the caudal putamen, are the first to degenerate in the initial phase of PD (Fearnley and Lees, ; Halliday et al., ; Blesa et al., ) indicating differential vulnerability... As the ventro-lateral SNpc/caudal putamen (habitual system) becomes dysfunctional in PD, the goal-directed system has to be recruited to perform the previously automatic habitual tasks... The activity and distribution of the synaptic dopamine transport (DAT) protein represents an entry for neurotoxic substances such MPTP and 6-OHDA (Dauer and Przedborski, )... DAT shows a dorso-ventral gradient with the expression of higher levels of glycosylated (mature, highly functional) protein found in the vulnerable ventral SNpc (Reyes et al., )... However, these neurons did not show a uniform expression of glycosylated DAT (Reyes et al., )... Together with the fact that other midbrain areas show glycosylated DAT, makes it unclear how these small expression differences could account for the differential vulnerability observed between SNpc and VTA neurons or between dorsal and ventral SNpc DA neurons (Gonzalez-Hernandez et al., )... Alternatively, another possible vulnerability feature for these neurons is their decreased vesicular accumulation of DA57 (Liang et al., ; Damier et al., ) and reduced levels of VMAT2 (Pifl et al., )... It remains to be ascertained if the latero-medial gradient of neuronal loss exhibited in the SNpc in PD is paralleled by degree of arborization... Thus, that at the onset of PD the neuronal cell loss is highly asymmetrical, and mainly affecting one unilateral sub-group of DA neurons that innervate sensorimotor territories of the caudal putamen... In rodents, these data are supported by observations that SNpc neurons also signal the initiation or termination of self-paced sequential behavior (Jin and Costa, )... This start/stop related activity emerged with learning, was specific for particular actions, and did not reflect timing or movement speed related actions... Thinking ahead, we realize that an ultimate research goal would be to replicate or simulate comparable levels of multitasking in suitable animal models to test the proposed hypothesis... This will pose a significant experimental challenge.

No MeSH data available.


Diagram of the functional loops involved in goal-directed and habitual behavior.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526812&req=5

Figure 1: Diagram of the functional loops involved in goal-directed and habitual behavior.

Mentions: The brain has two major systems for controlling behavior: a goal directed mechanism (GD) and a mechanism mediating stimulus-response habits (Figure 1). The goal directed system entails conscious, voluntary control of actions aimed toward obtaining rewards or avoiding punishments. Action selection is determined by competitions between relative outcome values, i.e. if outcome A is more valuable than outcome B, then learned behavior that will lead to outcome A will be selected. Examples of goal-directed control would be: heading to the fridge or going to a restaurant when we are hungry, taking the elevator or taking the stairs back to the apartment. This goal-directed process engages the prefrontal cortex and dorsolateral striatum (Yin et al., 2004). On the other hand, the habitual system detects well-learned cues that have been associated with specific responses, and therefore elicit automatic stimulus-response behavior via the re-entrant loop that connect sensorimotor cortical areas with the posterior putamen (dorsolateral striatum in rodents) (Barnes et al., 2005). Habits are established gradually over time. They evolve after many repetitions of a task being performed under flexible goal-directed learning and depend heavily on the statistical regularities between specific stimuli and consequent responses. Examples of habitual control would be, walking, riding a bike or driving. The critical test for habits is that they are resistant to outcome-devaluation (Adams and Dickinson, 1981). Inappropriate habitual responses are frequently difficult to eradicate and have to be corrected by goal-directed interventions after they fail to achieve their original intention. In this Opinion article we put forward the hypothesis that a significant factor that confers vulnerability to the ventro-lateral tier of SNpc at the onset of PD may reside in the key functional role that these neurons play in the performance of habitual behavior, switching between habitual and goal-directed control, and engaging both goal-directed and habitual control when carrying out multiple tasks simultaneously.


Habitual behavior and dopamine cell vulnerability in Parkinson disease.

Hernández LF, Redgrave P, Obeso JA - Front Neuroanat (2015)

Diagram of the functional loops involved in goal-directed and habitual behavior.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526812&req=5

Figure 1: Diagram of the functional loops involved in goal-directed and habitual behavior.
Mentions: The brain has two major systems for controlling behavior: a goal directed mechanism (GD) and a mechanism mediating stimulus-response habits (Figure 1). The goal directed system entails conscious, voluntary control of actions aimed toward obtaining rewards or avoiding punishments. Action selection is determined by competitions between relative outcome values, i.e. if outcome A is more valuable than outcome B, then learned behavior that will lead to outcome A will be selected. Examples of goal-directed control would be: heading to the fridge or going to a restaurant when we are hungry, taking the elevator or taking the stairs back to the apartment. This goal-directed process engages the prefrontal cortex and dorsolateral striatum (Yin et al., 2004). On the other hand, the habitual system detects well-learned cues that have been associated with specific responses, and therefore elicit automatic stimulus-response behavior via the re-entrant loop that connect sensorimotor cortical areas with the posterior putamen (dorsolateral striatum in rodents) (Barnes et al., 2005). Habits are established gradually over time. They evolve after many repetitions of a task being performed under flexible goal-directed learning and depend heavily on the statistical regularities between specific stimuli and consequent responses. Examples of habitual control would be, walking, riding a bike or driving. The critical test for habits is that they are resistant to outcome-devaluation (Adams and Dickinson, 1981). Inappropriate habitual responses are frequently difficult to eradicate and have to be corrected by goal-directed interventions after they fail to achieve their original intention. In this Opinion article we put forward the hypothesis that a significant factor that confers vulnerability to the ventro-lateral tier of SNpc at the onset of PD may reside in the key functional role that these neurons play in the performance of habitual behavior, switching between habitual and goal-directed control, and engaging both goal-directed and habitual control when carrying out multiple tasks simultaneously.

View Article: PubMed Central - PubMed

Affiliation: Fundacion HM, Hospital HM Puerta del Sur, Centre for Integrative Neuroscience A.C., Mostoles and CEU San Pablo University Madrid, Spain ; Center for Networked Biomedical Research on Neurodegenerative Diseases, Institute Carlos III Madrid, Spain.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

It is now well established that dopaminergic neurons in the ventro-lateral tier of the substantia nigra pars compacta (SNpc), which project mainly to the caudal putamen, are the first to degenerate in the initial phase of PD (Fearnley and Lees, ; Halliday et al., ; Blesa et al., ) indicating differential vulnerability... As the ventro-lateral SNpc/caudal putamen (habitual system) becomes dysfunctional in PD, the goal-directed system has to be recruited to perform the previously automatic habitual tasks... The activity and distribution of the synaptic dopamine transport (DAT) protein represents an entry for neurotoxic substances such MPTP and 6-OHDA (Dauer and Przedborski, )... DAT shows a dorso-ventral gradient with the expression of higher levels of glycosylated (mature, highly functional) protein found in the vulnerable ventral SNpc (Reyes et al., )... However, these neurons did not show a uniform expression of glycosylated DAT (Reyes et al., )... Together with the fact that other midbrain areas show glycosylated DAT, makes it unclear how these small expression differences could account for the differential vulnerability observed between SNpc and VTA neurons or between dorsal and ventral SNpc DA neurons (Gonzalez-Hernandez et al., )... Alternatively, another possible vulnerability feature for these neurons is their decreased vesicular accumulation of DA57 (Liang et al., ; Damier et al., ) and reduced levels of VMAT2 (Pifl et al., )... It remains to be ascertained if the latero-medial gradient of neuronal loss exhibited in the SNpc in PD is paralleled by degree of arborization... Thus, that at the onset of PD the neuronal cell loss is highly asymmetrical, and mainly affecting one unilateral sub-group of DA neurons that innervate sensorimotor territories of the caudal putamen... In rodents, these data are supported by observations that SNpc neurons also signal the initiation or termination of self-paced sequential behavior (Jin and Costa, )... This start/stop related activity emerged with learning, was specific for particular actions, and did not reflect timing or movement speed related actions... Thinking ahead, we realize that an ultimate research goal would be to replicate or simulate comparable levels of multitasking in suitable animal models to test the proposed hypothesis... This will pose a significant experimental challenge.

No MeSH data available.