Title: Effects of prenatal protein malnutrition on kindling-induced alterations in dentate granule cell excitability
Abstract: The effects of prenatal protein malnutrition on kindling-induced changes in inhibitory modulation of dentate granule cell activity were examined by analysis of extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to paired-pulse stimulation of the perforant pathway in freely-moving rats. Since we have shown that kindling results in enhanced synaptic transmission at the level of the perforant path/granule cell synapse (see preceding paper), we sought to determine if the kindling process might induce changes in inhibitory modulation of granule cell excitability which could be involved in the slower acquisition of the kindled state we have previously reported in malnourished animals. Beginning at 120–150 days of age, the response of dentate granule cells to paired-pulse stimulation of the perforant path was examined at interpulse intervals (IPIs) ranging from 20–1000 ms. A paired-pulse index (PPI) was constructed based on the mean percent change in population spike amplitudes of the two responses resulting from application of the pulse pair. PPI measures obtained during the kindling process were compared with individual prekindling measures to determine the mean percent change in excitatory/inhibitory modulation of granule cell activity. Significant inhibition of the second population response was apparent at all IPIs tested for both diet groups following the first kindled afterdischarge. This inhibition included significantly enhanced levels of inhibitory modulation during both the early (IPIs ≤ 40 ms) and late (IPIs ≥ 300 ms) inhibitory phase, as well as a complete disappearance of the facilitation phase (IPIs > 40 ms but <300 ms) which was replaced, following the first kindled afterdischarge, by inhibition of the second population response. The degree of enhancement in this inhibitory modulation of granule cell excitability was significantly greater in the animals of the malnourished group at all IPIs above 30 ms. Significantly enhanced levels of inhibition were maintained by animals of both diet groups throughout the kindling period, indicating that within the dentate gyrus, kindling is not accompanied by a decrease or loss of inhibitory modulation of granule cell activity. One week after cessation of kindling, however, the level of enhanced inhibition was found to be significantly reduced in animals of the 6%25% diet group, while animals of the control diet group continued to show levels of enhanced inhibitory activity of the same magnitude as those recorded following the first stage 5 convulsion. Our results indicate that prenatal protein malnutrition induces alterations in the activity of inhibitory systems modulating dentate granule cell activity resulting in significant enhancement of kindling-induced paired-pulse depression. These alterations appear to be transitory in animals of the 6%25% diet group, but of a more enduring nature in animals of the control diet group. We suggest that this enhancement of inhibition may be directly related to both the slower rate of kindling and the relative inability to consistently attain the kindled state which we have observed in malnourished animals. Paralleling results of the preceding paper, the effects of the prenatal dietary insult appear to be irreversible in mature animals even after a prolonged period of dietary rehabilitation.
Publication Year: 1991
Publication Date: 1991-05-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 67
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