Activation of microglia in acute hippocampal slices affects activity-dependent long-term potentiation and synaptic tagging and capture in area CA1

Raghuraman, Radha; Karthikeyan, A.; Wong, Lik-Wei; Dheen, S. Thameem; Sajikumar, Sreedharan

doi:10.1016/j.nlm.2019.107039

Cited by 16 publications

(12 citation statements)

References 66 publications

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“…Nevertheless, APP/PS1 mice had significantly shorter latencies at all key time points, indicating that tag setting process may be impaired partially. Our results show enhanced microglial activation in AD mice, females in particular are strengthened by our earlier finding showing the specific role of microglia in tag setting and STC (Raghuraman et al, 2019). We also observe a faster decay in LTP in APP/PS1 female mice, which suggests the possibility that the downstream mechanism of tag–PRPs interactions may have sex‐specific differences that warrant further investigations.…”

Section: Discussionsupporting

confidence: 88%

“…As previously discussed, sex differences in synaptic plasticity may be responsible for synaptic dysfunction in AD, but the accelerated pathology and the increased activation of microglia can also contribute towards impairments in neural plasticity. Microglia are essential for synaptic pruning, and aberrant microglial‐mediated engulfment of synapses in response to elevated Aβ plaque levels could conceivably impact synaptic transmission (Hong et al, 2016; Parihar & Brewer, 2010; Raghuraman et al, 2019). Alternatively, elevated Aβ levels in the extracellular microenvironment can also directly impact synaptic efficacy.…”

Section: Discussionmentioning

confidence: 99%

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Sex‐specific accelerated decay in time/activity‐dependent plasticity and associative memory in an animal model of Alzheimer's disease

et al. 2021

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Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event and appears before significant accumulation of amyloid plaques and neuronal degeneration. However, it is unclear whether sexual dimorphism at the synaptic level contributes to the higher risk and prevalence of AD in females. Our studies on APP/PS1 (APPSwe/PS1dE9) mouse model show that AD impacts hippocampal long‐term plasticity in a sex‐specific manner. Long‐term potentiation (LTP) induced by strong tetanic stimulation (STET), theta burst stimulation (TBS) and population spike timing‐dependent plasticity (pSTDP) show a faster decay in AD females compared with age‐matched AD males. In addition, behavioural tagging (BT), a model of associative memory, is specifically impaired in AD females with a faster decay in memory compared with males. Together with the plasticity and behavioural data, we also observed an upregulation of neuroinflammatory markers, along with downregulation of transcripts that regulate cellular processes associated with synaptic plasticity and memory in females. Immunohistochemistry of AD brains confirms that female APP/PS1 mice carry a higher amyloid plaque burden and have enhanced microglial activation compared with male APP/PS1 mice. Their presence in the diseased mice also suggests a link between the impairment of LTP and the upregulation of the inflammatory response. Overall, our data show that synaptic plasticity and associative memory impairments are more prominent in females and this might account for the faster progression of AD in females.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Sex‐specific accelerated decay in time/activity‐dependent plasticity and associative memory in an animal model of Alzheimer's disease

et al. 2021

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“…Clodronate treatment during the induction or early phase of LTP prevents the late LTP expression, suggesting a critical role of microglia in early STC and LTP induction. Disrupting microglia with clodronate after the establishment of late phase LTP has no effect on STC, as it does not block late LTP expression (Raghuraman et al, 2019). These results demonstrate that microglia play a significant role in setting the synaptic tags during the early phase of activity dependent plasticity which promote the stability of LTP.…”

Section: Microglia and Synaptic Plasticitymentioning

confidence: 77%

“…Synaptic plasticity is an ability of the CNS to modify synapses and neural connections in response to synaptic activity and sensory and motor experiences. Microglia are critically involved in the modulation of synaptic plasticity, including long-term potentiation (LTP) and longterm depression (LTD) (Table 2) (Raghuraman et al, 2019;Kim et al, 2020).…”

Section: Microglia Neuronal Activity and Synaptic Plasticitymentioning

confidence: 99%

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Microglia regulation of synaptic plasticity and learning and memory

Cornell¹,

Salinas²,

Huang³

et al. 2022

Neural Regen Res

165

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Microglia are the resident macrophages of the central nervous system. Microglia possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity. Through the C1q, C3 and CR3 “Eat Me” and CD47 and SIRPα “Don’t Eat Me” complement pathways, as well as other pathways such as CX3CR1 signaling, resting microglia regulate synaptic pruning, a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity. By mediating synaptic pruning, resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation, and also in the regulation of learning and memory, including the modulation of memory strength, forgetfulness, and memory quality. As a response to brain injury, infection or neuroinflammation, microglia become activated and increase in number. Activated microglia change to an amoeboid shape, migrate to sites of inflammation and secrete proteins such as cytokines, chemokines and reactive oxygen species. These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging, Alzheimer’s disease, traumatic brain injury, HIV-associated neurocognitive disorder, and other neurological or mental disorders such as autism, depression and post-traumatic stress disorder. With a focus mainly on recently published literature, here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory, as well as how activated microglia modulate disease-related plasticity and learning and memory deficits. By summarizing the function of microglia in these processes, we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory, and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging, Alzheimer’s disease, traumatic brain injury, HIV-associated neurocognitive disorder, and mental disorders.

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Long‐term depression induction and maintenance across regions of the apical branch of CA1 dendrites

et al. 2023

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Well known as the center for learning and memory, hippocampus is the crucial brain region to study synaptic plasticity in the context of cellular fundamental mechanisms such as long‐term depression (LTD) and long‐term potentiation (LTP). However, despite years of extensive research, the key to our LTD queries and their induction mechanisms has not been fully understood. Previously, we reported the induction of late‐LTD (L‐LTD) in the distally located synapses of apical branch of hippocampal CA1 dendrites using strong low‐frequency stimulation (SLFS). In contrast synapses at the proximal site could not express L‐LTD. Thus, in the present study, we wanted to investigate whether or not synapses of apical dendritic branch at the proximal location could induce and maintain LTD and its related properties in in vitro rat hippocampal slices. Results indicated that the SLFS in the distal and proximal region triggered the plasticity related proteins (PRP) synthesis in both regions, as evident by the induction and maintenance of L‐LTD in the distal region by virtue of synaptic and cross‐tagging. In addition, the application of emetine at the time of proximal input stimulation prevented the transition of early‐LTD (E‐LTD) into L‐LTD at the distal region, proving PRP synthesis at the proximal site. Further, it was observed that weak low‐frequency stimulation (WLFS) could induce E‐LTD in the proximal region along with LTD‐specific tag‐setting at the synapses. In conclusion, the current study suggests unique findings that the synaptic and cross‐tagging mediate L‐LTD expression is maintained in the proximal location of hippocampus apical CA1 dendrites.

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Activation of microglia in acute hippocampal slices affects activity-dependent long-term potentiation and synaptic tagging and capture in area CA1

Cited by 16 publications

References 66 publications

Sex‐specific accelerated decay in time/activity‐dependent plasticity and associative memory in an animal model of Alzheimer's disease

Sex‐specific accelerated decay in time/activity‐dependent plasticity and associative memory in an animal model of Alzheimer's disease

Microglia regulation of synaptic plasticity and learning and memory

Long‐term depression induction and maintenance across regions of the apical branch of CA1 dendrites

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