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Cellular mechanisms of hippocampal theta oscillations

海马θ振荡的细胞机制

基本信息

批准号：
10668962
负责人：
Andres Barria
金额：
$ 23.33万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10668962
关键词：
Acetylcholine Acute Alzheimer&apos s Disease Anatomy Animals Attenuated Bathing Behavior Brain Carbachol Cell Communication Cell model Cell physiology Cells Cholinergic Receptors Clinical Trials Cognition Communication Complex Disparity Epilepsy Frequencies Fresh Tissue Functional disorder Goals Hippocampus Human In Vitro Learning Mediating Membrane Membrane Potentials Memory Memory impairment Modeling Monkeys Mus Muscarinic Antagonists Neocortex Neuromodulator Neurons Outcome Periodicity Pharmacology Physiological Physiology Primates Process Property Pyramidal Cells Research Rodent Shapes Slice Stimulus Structure Study models System Testing Translating Washington Work basal forebrain cholinergic electric impedance electrical property experimental study hippocampal pyramidal neuron in vitro Model information processing memory encoding neocortical nervous system disorder neuronal circuitry nonhuman primate novel patch clamp pharmacologic response theories translation to humans voltage

项目摘要

PROJECT SUMMARY/ABSTRACT The mammalian brain has an incredible capacity to learn and store information that can be subsequently retrieved. A key brain structure that supports cognition and the formation of new memories is the hippocampus. Damage to the hippocampus impairs memory and results in debilitating maladies like Alzheimer's disease or epilepsy. Studies in primates and rodents have provided a rich systems-level understanding of hippocampal function and its interaction with other structures like neocortex. However, models that explain hippocampus physiology at the cellular and microcircuit level exclusively come from studies in rodents. Due in part to our limited understanding of the mechanisms that govern primate cellular physiology, treatments for complex neurological diseases have fared poorly when introduced in human clinical trials. Our long-range goal is to better understand how the primate hippocampus processes information in support of memory at the cellular and microcircuit level, thus connecting cellular physiology to network function in primates. Here we propose to develop a non-human primate model that allows the study of the cellular and microcircuit physiology of the primate hippocampus. We will combine whole-cell patch clamping and pharmacology in a novel in vitro approach to delineate the mechanisms that support theta oscillations in monkeys. Theta oscillations reflect temporally coordinated network activity in the hippocampus that occurs while attending to incoming stimuli and during successful memory encoding. They are present in both rodents and primates, but this activity only sparsely occurs in primates, suggesting that there are substantial differences in the neuronal circuits of the hippocampus and the properties of its neurons across species. To understand how cellular physiology shapes the theta oscillation in primates, we will both characterize the physiological properties of principal cells in the monkey hippocampus and the effect that the critical theta neuromodulator acetylcholine has in regulating the intrinsic properties of hippocampal neurons in vitro. The proposed experiments have the following potential outcomes: 1) establish whether the cellular physiology of pyramidal neurons in the hippocampus of monkeys differ from that of rodents, 2) identify mechanisms in monkeys at the cellular level that contribute to coordinated network activity. These experiments will provide species-specific evidence for a model that may translate better to human physiology.

项目总结/文摘