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Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines

View Article: PubMed Central - PubMed

ABSTRACT

Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain.

No MeSH data available.


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Microglia-spine interactions are modified after LTP induction.(A) A contact between a microglial process tip (green) and a dendritic spine (red) lasting for 90 s captured by time-lapse imaging (white arrow head, 2nd- 4th image). (B) Percentage of spines contacted in the field of view during basal synaptic transmission, integrated over 80 min. (C,D) The number of contacts did not change over time in the absence of the HFS protocol (C) (# contacts per 100 μm dendrite observed during 20 min of baseline: 5.2 ± 1.2; during 40′–60′: 5.0 ± 1.4; mean ± sem, paired t-test, p = 0.25, n = 7 slices). The number of microglia-spine contacts was decreased 40–60 min after LTP induction (blue) compared to its baseline conditions (black) (D) (from 3.6 ± 0.4 to 2.2 ± 0.4 contacts; mean ± sem, paired t-test, p = 0.04, n = 10 slices). (E) MIPs over 20 min showing the number of microglia-spine contacts on a hippocampal dendrite in baseline (5 contacts) (left panel) and LTP conditions (3 contacts, 40′–60′) (right). (F,G) The duration of microglia-spine contacts was constant in the absence of a HFS protocol (F) (contact duration during baseline: 1.5 min ± 0.1 min; during 40′–60′: 1.5 min ± 0.2 min; mean ± sem, paired t-test, p = 0.96, n = 7 slices). In contrast, contact durations were significantly enhanced 40–60 min after the induction of LTP compared to baseline conditions (G) (from 1.4 min ± 0.1 min to 2.1 min ± 0.2 min; mean ± sem, paired t-test, p = 0.006, n = 10 slices).
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f3: Microglia-spine interactions are modified after LTP induction.(A) A contact between a microglial process tip (green) and a dendritic spine (red) lasting for 90 s captured by time-lapse imaging (white arrow head, 2nd- 4th image). (B) Percentage of spines contacted in the field of view during basal synaptic transmission, integrated over 80 min. (C,D) The number of contacts did not change over time in the absence of the HFS protocol (C) (# contacts per 100 μm dendrite observed during 20 min of baseline: 5.2 ± 1.2; during 40′–60′: 5.0 ± 1.4; mean ± sem, paired t-test, p = 0.25, n = 7 slices). The number of microglia-spine contacts was decreased 40–60 min after LTP induction (blue) compared to its baseline conditions (black) (D) (from 3.6 ± 0.4 to 2.2 ± 0.4 contacts; mean ± sem, paired t-test, p = 0.04, n = 10 slices). (E) MIPs over 20 min showing the number of microglia-spine contacts on a hippocampal dendrite in baseline (5 contacts) (left panel) and LTP conditions (3 contacts, 40′–60′) (right). (F,G) The duration of microglia-spine contacts was constant in the absence of a HFS protocol (F) (contact duration during baseline: 1.5 min ± 0.1 min; during 40′–60′: 1.5 min ± 0.2 min; mean ± sem, paired t-test, p = 0.96, n = 7 slices). In contrast, contact durations were significantly enhanced 40–60 min after the induction of LTP compared to baseline conditions (G) (from 1.4 min ± 0.1 min to 2.1 min ± 0.2 min; mean ± sem, paired t-test, p = 0.006, n = 10 slices).

Mentions: While it was shown before that microglial processes can contact synapses416, little quantitative information exists on the frequency and dynamics of these interactions during basal synaptic transmission. To this end, we identified microglia-spine contacts, which we defined as a close physical apposition (i.e. <400 nm), in the time series of 3D image stacks, and analyzed their number and duration (Fig. 3A).


Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines
Microglia-spine interactions are modified after LTP induction.(A) A contact between a microglial process tip (green) and a dendritic spine (red) lasting for 90 s captured by time-lapse imaging (white arrow head, 2nd- 4th image). (B) Percentage of spines contacted in the field of view during basal synaptic transmission, integrated over 80 min. (C,D) The number of contacts did not change over time in the absence of the HFS protocol (C) (# contacts per 100 μm dendrite observed during 20 min of baseline: 5.2 ± 1.2; during 40′–60′: 5.0 ± 1.4; mean ± sem, paired t-test, p = 0.25, n = 7 slices). The number of microglia-spine contacts was decreased 40–60 min after LTP induction (blue) compared to its baseline conditions (black) (D) (from 3.6 ± 0.4 to 2.2 ± 0.4 contacts; mean ± sem, paired t-test, p = 0.04, n = 10 slices). (E) MIPs over 20 min showing the number of microglia-spine contacts on a hippocampal dendrite in baseline (5 contacts) (left panel) and LTP conditions (3 contacts, 40′–60′) (right). (F,G) The duration of microglia-spine contacts was constant in the absence of a HFS protocol (F) (contact duration during baseline: 1.5 min ± 0.1 min; during 40′–60′: 1.5 min ± 0.2 min; mean ± sem, paired t-test, p = 0.96, n = 7 slices). In contrast, contact durations were significantly enhanced 40–60 min after the induction of LTP compared to baseline conditions (G) (from 1.4 min ± 0.1 min to 2.1 min ± 0.2 min; mean ± sem, paired t-test, p = 0.006, n = 10 slices).
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f3: Microglia-spine interactions are modified after LTP induction.(A) A contact between a microglial process tip (green) and a dendritic spine (red) lasting for 90 s captured by time-lapse imaging (white arrow head, 2nd- 4th image). (B) Percentage of spines contacted in the field of view during basal synaptic transmission, integrated over 80 min. (C,D) The number of contacts did not change over time in the absence of the HFS protocol (C) (# contacts per 100 μm dendrite observed during 20 min of baseline: 5.2 ± 1.2; during 40′–60′: 5.0 ± 1.4; mean ± sem, paired t-test, p = 0.25, n = 7 slices). The number of microglia-spine contacts was decreased 40–60 min after LTP induction (blue) compared to its baseline conditions (black) (D) (from 3.6 ± 0.4 to 2.2 ± 0.4 contacts; mean ± sem, paired t-test, p = 0.04, n = 10 slices). (E) MIPs over 20 min showing the number of microglia-spine contacts on a hippocampal dendrite in baseline (5 contacts) (left panel) and LTP conditions (3 contacts, 40′–60′) (right). (F,G) The duration of microglia-spine contacts was constant in the absence of a HFS protocol (F) (contact duration during baseline: 1.5 min ± 0.1 min; during 40′–60′: 1.5 min ± 0.2 min; mean ± sem, paired t-test, p = 0.96, n = 7 slices). In contrast, contact durations were significantly enhanced 40–60 min after the induction of LTP compared to baseline conditions (G) (from 1.4 min ± 0.1 min to 2.1 min ± 0.2 min; mean ± sem, paired t-test, p = 0.006, n = 10 slices).
Mentions: While it was shown before that microglial processes can contact synapses416, little quantitative information exists on the frequency and dynamics of these interactions during basal synaptic transmission. To this end, we identified microglia-spine contacts, which we defined as a close physical apposition (i.e. <400 nm), in the time series of 3D image stacks, and analyzed their number and duration (Fig. 3A).

View Article: PubMed Central - PubMed

ABSTRACT

Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain.

No MeSH data available.


Related in: MedlinePlus