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Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition
J D Bronzino1, J H Blaise, D J Mokler
1Department of Engineering, Trinity College, 300 Summit Street, Hartford, CT, USA. joseph.bronzino@mail.trincoll.edu
Insights
Prenatal protein malnutrition alters dentate granule cell excitability in young rats, affecting synaptic transmission shifts during development. These effects are most pronounced in early life, normalizing by adulthood.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Prenatal protein malnutrition is a significant concern impacting neurodevelopment.
- Hippocampal neuroplasticity is crucial for cognitive functions and is sensitive to early-life nutrition.
- Vigilance states (quiet waking, sleep stages) influence brain activity and development.
Purpose of the Study:
- To investigate the long-term effects of prenatal protein malnutrition on hippocampal neuroplasticity.
- To examine how malnutrition modulates dentate granule cell excitability across different developmental stages and vigilance states.
- To determine the impact of malnutrition on synaptic transmission shifts during maturation.
Main Methods:
- Utilized freely moving rats at 15, 30, and 90 days of age.
- Employed paired-pulse stimulation of the medial perforant path to measure dentate granule cell excitability via the paired-pulse index (PPI).
- Analyzed PPI using population spike amplitude (PSA) and EPSP slope measures across quiet waking, slow-wave sleep, and REM sleep.
Main Results:
- Prenatal protein malnutrition altered PPI in early development (15 and 30 days) but not in adulthood.
- Malnourished rats showed altered inhibition/facilitation patterns at specific inter-pulse intervals and vigilance states.
- A shift in vigilance state-dependent synaptic transmission from REM sleep to SWS occurred later in malnourished animals compared to controls.
Conclusions:
- Prenatal protein malnutrition significantly impacts dentate granule cell excitability modulation during early development.
- Vigilance states play a role in synaptic transmission, with a developmental shift from REM to SWS.
- The effects of prenatal malnutrition on hippocampal excitability are stage-specific and diminish by adulthood.
Abstract:
Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.
