Related Experiment Videos
Activation of mesocortical dopaminergic system in the rat in response to neonatal medial prefrontal cortex lesions.
J M de Brabander1, C G van Eden, J P de Bruin
1The Netherlands Institute for Brain Research, Amsterdam.
Insights
Neonatal lesions to the rat medial prefrontal cortex (mPFC) spared function and increased dopamine (DA) innervation. This suggests the mesocortical DA system is crucial for sparing, but not the sole factor.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neuroplasticity
Background:
- Neonatal brain injury can lead to functional sparing.
- The medial prefrontal cortex (mPFC) plays a role in cognitive functions.
- Dopaminergic (DA) systems are implicated in brain development and function.
Purpose of the Study:
- To investigate the effects of neonatal mPFC lesions on spatial delayed alternation (SDA) performance.
- To examine changes in dopaminergic (DA) innervation within the rat mPFC following neonatal lesions.
- To explore the role of the mesocortical DA system in functional sparing after early-life brain injury.
Main Methods:
- Neonatal lesions of the medial prefrontal cortex (mPFC) were induced in 6-day-old rats.
- Spatial delayed alternation (SDA) task was used to assess cognitive performance.
- Immunohistochemistry and biochemical assays were employed to quantify DA innervation, concentration, and metabolite levels (DOPAC, HVA).
Main Results:
- Neonatal mPFC lesions resulted in sparing of SDA performance.
- Increased DA innervation, characterized by higher fiber density and thicker fibers, was observed in the remaining mPFC.
- Concentrations of DA, DOPAC, and HVA were significantly elevated in the lesioned mPFC, while DA utilization remained unchanged.
Conclusions:
- The mesocortical DA system is involved in the neural mechanisms underlying functional sparing after neonatal mPFC lesions.
- Enhanced DA innervation and increased DA levels in the remaining mPFC support the role of this system in sparing.
- Functional sparing observed in the absence of discernible mPFC suggests that the DA response is not the sole contributor to this phenomenon.
Abstract:
Neonatal lesions of the medial part of the rat prefrontal cortex (mPFC) (performed at the age of 6 days) resulted in a sparing in the performance of spatial delayed alternation (SDA) and an increase in dopaminergic (DA) innervation. The increased DA innervation was primarily observed in the remaining part of the mPFC. The DA fibre density was considerably higher in the non-ablated part of the mPFC, and the fibres were thicker with more large varicosities compared with sham-operated controls. Biochemical measurements showed a 3.5-fold increase in DA concentration in the remaining part of the mPFC of the animals with neonatal lesions when compared with the mPFC of sham-operated animals. In addition the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased. The metabolite/transmitter ratios, indicating DA utilisation, did not significantly differ from controls. The increased DA innervation and the increased concentration of DA and its metabolites in the animals with neonatal lesions further support our hypothesis that the mesocortical DA system is involved in the neural mechanism of sparing of function observed after neonatal mPFC lesions. However, sparing of function in animals with no discernable mPFC forces us to conclude that this DA response cannot be the only factor involved in the mechanism of sparing of function.