Evidence that cholinergic mechanisms contribute to hyperexcitability at early stages in Alzheimer's disease.

A long-standing theory for Alzheimer's disease (AD) has been that deterioration of synapses and depressed neuronal activity is a major contributing factor. We review the increasing evidence, in humans and in mouse models, that show that there is often neuronal hyperactivity at early stages rather than decreased activity. We discuss studies in mouse models showing that hyperexcitability can occur long before plaque deposition and memory impairment.

Developing forebrain synapses are uniquely vulnerable to sleep loss.

Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function and a locus of dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic during development, becoming stabilized with maturation to adulthood, suggesting sleep exerts distinct synaptic functions between development and adulthood.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse.

Dentate Gyrus Granule Cells Show Stability of BDNF Protein Expression in Mossy Fiber Axons with Age, and Resistance to Alzheimer's Disease Neuropathology in a Mouse Model.

Brain-derived neurotrophic factor (BDNF) is important in the development and maintenance of neurons and their plasticity. Hippocampal BDNF has been implicated in Alzheimer's disease (AD) because hippocampal levels in AD patients and AD animal models are often downregulated, suggesting that reduced BDNF contributes to AD. However, the location where hippocampal BDNF protein is most highly expressed, the mossy fiber (MF) axons of dentate gyrus granule cells (GCs), has been understudied, and not in controlled conditions.

Developing forebrain synapses are uniquely vulnerable to sleep loss.

Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function and a locus of dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic during development, becoming stabilized with maturation to adulthood, suggesting sleep exerts distinct synaptic functions between development and adulthood.

Stability of dentate gyrus granule cell mossy fiber BDNF protein expression with age and resistance of granule cells to Alzheimer's disease neuropathology in a mouse model.

The neurotrophin brain-derived neurotrophic factor (BDNF) is important in development and maintenance of neurons and their plasticity. Hippocampal BDNF has been implicated Alzheimer's disease (AD) because hippocampal levels in AD patients and AD animal models are consistently downregulated, suggesting that reduced BDNF contributes to AD. However, the location where hippocampal BDNF protein is most highly expressed, the mossy fiber (MF) axons of dentate gyrus (DG) granule cells (GCs), has been understudied, and never in controlled conditions.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse.

Early changes in synaptic and intrinsic properties of dentate gyrus granule cells in a mouse model of Alzheimer's disease neuropathology and atypical effects of the cholinergic antagonist atropine.

It has been reported that hyperexcitability occurs in a subset of patients with Alzheimer's disease (AD) and hyperexcitability could contribute to the disease. Several studies have suggested that the hippocampal dentate gyrus (DG) may be an important area where hyperexcitability occurs. Therefore, we tested the hypothesis that the principal DG cell type, granule cells (GCs), would exhibit changes at the single-cell level which would be consistent with hyperexcitability and might help explain it.