Rapid Aging in the Perforant Path Projections to the Rodent Dentate Gyrus
| العنوان: | Rapid Aging in the Perforant Path Projections to the Rodent Dentate Gyrus |
|---|---|
| المؤلفون: | Brittney M. Cox, Aliza A. Le, Christine M. Gall, Julie C. Lauterborn, Julian Quintanilla, Conor D. Cox, Gary Lynch, Mohammad Amani, Weisheng Wang |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 41, iss 10 J Neurosci |
| بيانات النشر: | eScholarship, University of California, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Aging, Long-Term Potentiation, Neurodegenerative, Inbred C57BL, Alzheimer's Disease, Medical and Health Sciences, memory, Mice, 0302 clinical medicine, Research Articles, lateral perforant path, biology, General Neuroscience, TrkB, Long-term potentiation, medicine.anatomical_structure, Neurological, Excitatory postsynaptic potential, 1.1 Normal biological development and functioning, Perforant Pathway, 03 medical and health sciences, Underpinning research, medicine, Acquired Cognitive Impairment, Animals, Rats, Long-Evans, Neurology & Neurosurgery, entorhinal cortex, Dentate gyrus, Psychology and Cognitive Sciences, Neurosciences, Long-Evans, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Entorhinal cortex, Perforant path, Rats, Brain Disorders, Mice, Inbred C57BL, Electrophysiology, 030104 developmental biology, Synaptic plasticity, Dentate Gyrus, Synaptophysin, biology.protein, Dementia, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Why layers II/III of entorhinal cortex (EC) deteriorate in advance of other regions during the earliest stages of Alzheimer's disease is poorly understood. Failure of retrograde trophic support from synapses to cell bodies is a common cause of neuronal atrophy, and we accordingly tested for early-life deterioration in projections of rodent layer II EC neurons. Using electrophysiology and quantitative imaging, changes in EC terminals during young adulthood were evaluated in male rats and mice. Field excitatory postsynaptic potentials, input/output curves, and frequency following capacity by lateral perforant path (LPP) projections from lateral EC to dentate gyrus were unchanged from 3 to 8–10 months of age. In contrast, the unusual presynaptic form of long-term potentiation (LTP) expressed by the LPP was profoundly impaired by 8 months in rats and mice. This impairment was accompanied by a reduction in the spine to terminal endocannabinoid signaling needed for LPP-LTP induction and was offset by an agent that enhances signaling. There was a pronounced age-related increase in synaptophysin within LPP terminals, an effect suggestive of incipient pathology. Relatedly, presynaptic levels of TrkB—receptors mediating retrograde trophic signaling—were reduced in the LPP terminal field. LTP and TrkB content were also reduced in the medial perforant path of 8- to 10-month-old rats. As predicted, performance on an LPP-dependent episodic memory task declined by late adulthood. We propose that memory-related synaptic plasticity in EC projections is unusually sensitive to aging, which predisposes EC neurons to pathogenesis later in life.SIGNIFICANCE STATEMENTNeurons within human superficial entorhinal cortex are particularly vulnerable to effects of aging and Alzheimer's disease, although why this is the case is not understood. Here we report that perforant path projections from layer II entorhinal cortex to the dentate gyrus exhibit rapid aging in rodents, including reduced synaptic plasticity and abnormal protein content by 8–10 months of age. Moreover, there was a substantial decline in the performance of an episodic memory task that depends on entorhinal cortical projections at the same ages. Overall, the results suggest that the loss of plasticity and related trophic signaling predispose the entorhinal neurons to functional decline in relatively young adulthood. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2345908c31c673fecc3a966c219036b https://escholarship.org/uc/item/8n1819dh |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f2345908c31c673fecc3a966c219036b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |