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Early septal lesion: effect on the development of the cholinergic system in rat hippocampus
Insights
Early septal lesions in rats significantly reduced acetylcholinesterase (AChE) levels in the hippocampus, indicating age-dependent plasticity. However, muscarinic binding site development remained unaffected by these early deafferentations.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurochemistry
Background:
- The cholinergic system, particularly the septohippocampal pathway, is crucial for hippocampal function.
- Understanding the developmental plasticity of this system is key to comprehending neurological development and recovery.
- Acetylcholinesterase (AChE) and muscarinic receptors are key markers of cholinergic system development.
Purpose of the Study:
- To investigate the impact of early postnatal septal lesions on the development of the cholinergic system in the rat hippocampus.
- To determine the age-dependent plasticity of the septohippocampal connections.
- To assess the development of muscarinic binding sites following early deafferentation.
Main Methods:
- Performed septal lesions in rats at 2-4 days postnatal, before septohippocampal connections are established.
- Measured acetylcholinesterase (AChE) activity at maturity in lesioned and control animals.
- Quantified muscarinic binding sites using [3H]quinuclidinyl benzilate ([3H]QNB) binding assays in hippocampal tissue.
Main Results:
- Early lesions led to a significant reduction in mature hippocampal AChE levels (approx. 30% of control), suggesting impaired cholinergic development.
- Adult animals with lesions sustained in adulthood showed a more severe reduction in AChE levels (approx. 15% of control), indicating age-dependent plasticity.
- Despite hippocampal atrophy, the development of muscarinic binding sites was not altered; [3H]QNB binding per protein remained similar to controls.
Conclusions:
- The development of muscarinic binding sites in the rat hippocampus is independent of the normal establishment of septohippocampal presynaptic contacts.
- Early deafferentation of the septohippocampal pathway results in reduced AChE levels, but the system exhibits age-dependent plasticity in response to such insults.
Abstract:
The development of the cholinergic system in the rat hippocampal formation was studied following lesion of the septal region at an age 2--4 days postnatal (i.e. the lesion was performed prior to the establishment of the septohippocampal connections). The steep increase in acetylcholinesterase (AChE) level, that under normal conditions takes place during the second and the third week postnatal, was not observed in early lesioned animals, and AChE level at maturity was about 30% of control. AChE level of adult-lesioned animals was about 15% of control, suggesting an age-dependent plasticity in response to the lesion. Early deafferentation did not seem to alter the pattern of development of muscarinic binding sites as measured by specific binding of [3H]quinuclidinyl benzilate ([3H]QNB). Total [3H]QNB bound per hippocampus of adult, early-lesioned animals was about 70% of control, but this reduction could be accounted for by the atrophy observed in the hippocampal formation following early lesion. Binding of [3H]QNB per protein in early lesioned animals did not differ from normal. Thus the development and the level of muscarinic binding sites in the hippocampal formation do not seem to depend upon normal establishment of presynaptic contacts.