THE ROLE OF DOPAMINE IN NEURONAL PLASTICITY AND LEARNING AND MEMORY IN RATS, IN MODELS OF DOPAMINE DEFICIENCY AND IN PARKINSON’S DISEASE PATIENTS

Abstract: 

Dopaminergic innervation in the prefrontal cortex (PFC) and hippocampus plays a critical role in many cognitive processes. Moreover, interactions between dopamine and glutamate receptors are essential for the PFC and hippocampal cognitive functions.

The aim of this project is to investigate the molecular basis by which Dopamine D1 receptors interact with glutamate NMDA receptors and how this interaction affects LTP (Long Term Potentiation) and cognitive function. Furthermore, the project will investigate the molecular mechanisms underlying cognitive function impairment in dopamine-deficient animal models and in Parkinson's disease (PD) patients.

Objectives:

  • Role of Dopamine in synaptic plasticity and learning memory: Using an in vivo œnovelty stimulus (exposing the rats to a novel environment) we will investigate the functional status and consequences of the D1/NMDA synergistic interaction seen in our previous in vitro work (Sarantis et al. 2009), by examining the involvement of D1/NMDA synergism: i) on the activation/phosphorylation of NMDA/AMPA receptors and ERK1/2 kinases, ii) on the expression of immediate early genes (IEGs) and histone remodelling iii) on the induction and maintenance of LTP, iv) on the hippocampal neurogenesis, likely induced by the novelty stimulus, v) on the effect of early novelty experiences on the dopaminergic system in adulthood.
  • The effect of dopamine deficiency on cognitive processes: Using genetic models of dopamine deficiency with impaired cognitive function we will examine the function of D1/NMDA synergism after the œnovelty stimulus.
  • Effect of 'deep' electrical brain stimulation (DBS) in cerebral blood flow and cognitive function in PD patients.

The aim of this study is the functional imaging of cerebral blood flow (using SPECT) in patients undergoing DBS surgery, and the correlation of the findings with possible changes in cognitive functions of the patient.

Project info

Acronym:
upatras2
Coordinating Institution:
University of Patras
Scientific Coordinator:
Angelatou Fevronia
Research Team 2 Leader:
Matsokis Nikolaos
Research Team 3 Leader:
Constantoyannis Constantinos

Stats

I.D.:
972
Mis:
380342
Duration (months):
45
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4ΘΗ9-ΥΡ0

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