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Abstract Perisynaptic astroglia provide critical molecular and structural support to regulate synaptic transmission and plasticity in the nanodomain of the axon-spine interface. Three-dimensional reconstruction from serial section electron microscopy (3DEM) was used to investigate relationships between perisynaptic astroglia and dendritic spine synapses undergoing plasticity in the hippocampus of awake adult male rats. Delta-burst stimulation (DBS) of the medial perforant pathway induced long-term potentiation (LTP) in the middle molecular layer and concurrent long-term depression (cLTD) in the outer molecular layer of the dentate gyrus. The contralateral hippocampus received baseline stimulation as a within-animal control. Brains were obtained 30 minutes or 2 hours after DBS onset. An automated 3DEM pipeline was developed to enable unbiased quantification of astroglial coverage at the perimeter of the axon-spine interface. Under all conditions, >85% of synapses had perisynaptic astroglia processes within 120 nm of some portion of the perimeter. LTP broadened the distribution of spine sizes while reducing the presence and proximity of perisynaptic astroglia near the axon-spine interface of large spines. In contrast, cLTD transiently reduced the length of the axon-spine interface perimeter without substantially altering astroglial apposition. The postsynaptic density was discovered to be displaced from the center of the axon-spine interface, with this offset increasing during LTP and decreasing during cLTD. Astroglial access to the postsynaptic density was diminished during LTP and enhanced during cLTD, in parallel with changes in spine size. Thus, access of perisynaptic astroglia to synapses is dynamically modulated during LTP and cLTD alongside synaptic remodeling. Significance StatementPerisynaptic astroglia provide critical molecular and structural regulation of synaptic plasticity underlying learning and memory. The hippocampal dentate gyrus, a brain region crucial for learning and memory, was found to have perisynaptic astroglia at the axon-spine interface of >85% of excitatory synapses measured. Long-term potentiation triggered the retraction of perisynaptic astroglia processes selectively from large synapses. This retraction decreased access of perisynaptic astroglia to the postsynaptic density, which was discovered to be located off-center in the axon-spine interface. Concurrent long-term depression temporarily (< 2 h) decreased spine perimeter and thus increased access of synapses to perisynaptic astroglia. These findings provide new insights into how the structural dynamics of spines and synapses shape access to perisynaptic astroglia.
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Locus coeruleus in memory formation and Alzheimer's disease
Abstract Catecholamine neurons of the locus coeruleus (LC) in the dorsal pontine tegmentum innervate the entire neuroaxis, with signaling actions implicated in the regulation of attention, arousal, sleep–wake cycle, learning, memory, anxiety, pain, mood, and brain metabolism. The co‐release of norepinephrine (NE) and dopamine (DA) from LC terminals in the hippocampus plays a role in all stages of hippocampal‐memory processing. This catecholaminergic regulation modulates the encoding, consolidation, retrieval, and reversal of hippocampus‐based memory. LC neurons in awake animals have two distinct firing modes: tonic firing (explorative) and phasic firing (exploitative). These two firing modes exert different modulatory effects on post‐synaptic dendritic spines. In the hippocampus, the firing modes regulate long‐term potentiation (LTP) and long‐term depression, which differentially regulate the mRNA expression and transcription of plasticity‐related proteins (PRPs). These proteins aid in structural alterations of dendritic spines, that is, structural long‐term potentiation (sLTP), via expansion and structural long‐term depression (sLTD) via contraction of post‐synaptic dendritic spines. Given the LC's role in all phases of memory processing, the degeneration of 50% of the LC neuron population occurring in Alzheimer's disease (AD) is a clinically relevant aspect of disease pathology. The loss of catecholaminergic regulation contributes to dysfunction in memory processes along with impaired functions associated with attention and task completion. The multifaceted role of the LC in memory and general task performance and the close correlation of LC degeneration with neurodegenerative disease progression together implicate it as a target for new clinical assessment tools.
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- Award ID(s):
- 1926781
- PAR ID:
- 10359791
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- European Journal of Neuroscience
- Volume:
- 54
- Issue:
- 8
- ISSN:
- 0953-816X
- Page Range / eLocation ID:
- p. 6948-6959
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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