Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

AbstractDopaminergic neurons of the substantia nigra (SNC) and ventral tegmental area (VTA) exhibit spontaneous firing activity. The dopaminergic neurons in these regions have been shown to exhibit differential sensitivity to neuronal loss and psychostimulants targeting dopamine transporter. However, it remains unclear whether these regional differences scale beyond individual neuronal activity to regional neuronal networks. Here we utilized live-cell calcium imaging to show that network connectivity greatly differs between SNC and VTA regions with higher incidence of hub-like neurons in the VTA. Specifically, the frequency of hub-like neurons was significantly lower in SNC dopamine neurons than in the adjacent VTA, consistent with the interpretation of a lower network resilience to SNC neuronal loss. We tested this hypothesis when activity of an individual dopaminergic neuron is suppressed, through whole-cell patch clamp electrophysiology, in either SNC, or VTA networks. Neuronal loss in the SNC decreased network clustering, whereas the larger number of hub-neurons in the VTA overcompensated by increasing network clustering in the VTA. We further show that network properties are regulatable via a dopamine transporter but not a D2 receptor dependent mechanism. Our results demonstrate novel regulatory mechanisms of functional network topology in dopaminergic brain regions.

Download Full-text

PT545. The Direct Protein-Protein Interaction between Dopamine Transporter and Dopamine D2 Receptor: A Novel Target Site to Modulate Synaptic Dopamine

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyw044.545 ◽

2016 ◽

Vol 19 (Suppl_1) ◽

pp. 1-2

Keyword(s):

Dopamine Transporter ◽

Protein Interaction ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

Target Site ◽

Protein Protein Interaction ◽

Dopamine D2 ◽

Novel Target

Download Full-text

Intrinsic exercise capacity in rats influences dopamine neuroplasticity induced by physical training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00506.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1721-1729 ◽

Cited By ~ 4

Author(s):

Patrícia C. R. Rabelo ◽

Nayara A. C. Horta ◽

Letícia M. S. Cordeiro ◽

Maristela O. Poletini ◽

Cândido C. Coimbra ◽

...

Keyword(s):

Tyrosine Hydroxylase ◽

Cell Line ◽

Dopamine Transporter ◽

Physical Training ◽

Neurotrophic Factor ◽

D2 Receptor ◽

D1 Receptor ◽

Mrna Levels ◽

Glia Cell ◽

Intrinsic Capacity

The study evaluates whether the intrinsic capacity for physical exercise influences dopamine neuroplasticity induced by physical training. Male rats were submitted to three progressive tests until fatigue. Based on the maximal time of exercise (TE), rats were considered as low performance (LP), standard performance (SP) or high performance (HP) to exercise. Eight animals from each group (LP, SP, and HP) were randomly subdivided in sedentary (SED) or trained (TR). Physical training was performed for 6 wk. After that, concentrations of dopamine (DA), serotonin (5-HT), and their metabolites and mRNA levels of D1 receptor ( Drd1), D2 receptor ( Drd2), dopamine transporter ( Dat), tyrosine hydroxylase ( Th), glia cell line neurotrophic factor ( Gdnf), and brain-derived neurotrophic factor ( Bdnf) were determined in the caudate-putamen (CPu). TE was increased with training in all performance groups. However, the relative increase was markedly higher in LP rats, and this was associated with a training-induced increase in dopaminergic activity in the CPu, which was determined by the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. An opposite monoamine response was found in HP-TR rats, in which physical training decreased the DOPAC/DA ratio in the CPu. Moreover, LP-SED rats displayed higher levels of Drd2 in the CPu compared with the other SED groups, and this higher expression was decreased by physical training. Physical training also decreased Dat and increased Gdnf in the CPu of LP rats. Physical training decreased Bdnf in the CPu only in HP rats. Thus, we provide evidence that the intrinsic capacity to exercise affects the neuroplasticity of the dopaminergic system in response to physical training. NEW & NOTEWORTHY The findings reported reveal that dopaminergic neuroplasticity in caudate-putamen induced by physical training is influenced by the intrinsic capacity to exercise in rats. To evaluate the dopaminergic neuroplasticity, we analyzed mRNA levels of D1 receptor, D2 receptor, dopamine transporter, tyrosine hydroxylase, glia cell line neurotrophic factor, and brain-derived neurotrophic factor as well as concentrations of dopamine, serotonin, and their metabolites. These results expand our knowledge about the interrelationship between genetic background, physical training, and dopaminergic neuroplasticity.

Download Full-text