Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex - PubMed (original) (raw)

Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex

Guang Yang et al. Anesthesiology. 2011 Oct.

Abstract

Background: Anesthetics are widely used to induce unconsciousness, pain relief, and immobility during surgery. It remains unclear whether the use of anesthetics has significant and long-lasting effects on synapse development and plasticity in the brain. To address this question, the authors examined the formation and elimination of dendritic spines, postsynaptic sites of excitatory synapses, in the developing mouse cortex during and after anesthetics exposure.

Methods: Transgenic mice expressing yellow fluorescence protein in layer 5 pyramidal neurons were used in this study. Mice at 1 month of age underwent ketamine-xylazine and isoflurane anesthesia over a period of hours. The elimination and formation rates of dendritic spines and filopodia, the precursors of spines, were followed over hours to days in the primary somatosensory cortex using transcranial two-photon microscopy. Four to five animals were examined under each experimental condition. Student t test and Mann-Whitney U test were used to analyze the data.

Results: Administration of either ketamine-xylazine or isoflurane rapidly altered dendritic filopodial dynamics but had no significant effects on spine dynamics. Ketamine-xylazine increased filopodial formation whereas isoflurane decreased filopodial elimination during 4 h of anesthesia. Both effects were transient and disappeared within a day after the animals woke up.

Conclusion: Studies suggest that exposure to anesthetics transiently affects the dynamics of dendritic filopodia but has no significant effect on dendritic spine development and plasticity in the cortex of 1-month-old mice.

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Figures

Fig. 1

Fig. 1

Administration of ketamine-xylazine rapidly increased the formation of dendritic filopodia but not spines over hours. A-B, In vivo time-lapse imaging of same dendritic segments over 4 h in the primary somatosensory cortex of 1-month-old animals that received no anesthesia (A) or ketamine-xylazine (K-X) anesthesia (B). Most dendritic spines on the same dendritic branches remained stable over 4 h whereas filopodia (asterisks) underwent rapid turnover. Scale bar, 2 μm. C-D, Percentage of newly formed (C) and eliminated (D) dendritic spines over 1 and 4 h. Administration of K-X did not alter spine dynamics. E-F, Percentage of newly formed (E) and eliminated (F) dendritic filopodia over 1 and 4 h. K-X anesthesia led to a rapid increase of filopodial formation but had no effect on filopodial elimination. Percentages were calculated as the number of spines/filopodia formed or eliminated divided by the number of pre-existing spines/filopodia. Each filled circle represents a single animal. Data are presented as mean ± S.D. ** P < 0.01; *** P < 0.001.

Fig. 2

Fig. 2

Ketamine-xylazine has no long lasting effects on the formation and elimination rates of dendritic spines and filopodia. A, Animals were under Ketamine-xylazine (K-X) anesthesia for the first 4 h and recovered for the next 8 h. B-C, Percentage of newly formed (B) and eliminated (C) dendritic spines over 12 h. D-E, Percentage of newly formed (D) and eliminated (E) dendritic filopodia over 12 h. There was no significant difference in spine or filopodial formation and elimination over 12 h between animals with and without K-X anesthesia. Percentages were calculated as the number of spines/filopodia formed or eliminated divided by the number of pre-existing spines/filopodia. Each filled circle represents a single animal. Data are presented as mean ± S.D.

Fig. 3

Fig. 3

The majority of newly formed filopodia and spines do not persist. A, The percentage of new filopodia formed over the first 4 h that were eliminated, that persisted as filopodia, or that were transformed to spines over the next 8 h. The majority of filopodia were eliminated, a small percentage persisted, and less than 10% of filopodia were transformed to spines. There was no significant difference between filopodia formed with and without Ketamine-xylazine (K-X). B, Percentage of new spines persisting for 8 h. Less than half of new spines formed within the first 4 h persisted for the next 8 h. There was no significant difference between spines formed with and without K-X. C, Percentage of new spines persisting for 1 month. Less than 7% of new spines formed within 12 h or 2 days persisted over 1 month. Each filled circle represents a single animal. Data are presented as mean ± S.D.

Fig. 4

Fig. 4

Systemic administration of MK801 mimics Ketamine-xylazine induced filopodial formation. A, Percentage of newly formed dendritic filopodia over 4 and 12 h. Animals were injected with MK801 after the first imaging session and re-imaged 4 and 12 h later. MK801 injection caused a rapid increase of filopodial formation over 4 but not 12 h. B, Percentage of eliminated dendritic filopodia over 4 and 12 h. MK801 had no significant effects on filopodial elimination. Percentages were calculated as the number of filopodia formed or eliminated divided by the number of pre-existing filopodia. Each filled circle represents a single animal. Data are presented as mean ± S.D. ***P < 0.001.

Fig. 5

Fig. 5

Administration of isoflurane affects the dynamics of dendritic filopodia but not spines. A, In vivo time-lapse imaging of the same dendritic segments over 4 h in 1-month-old, isoflurane anesthetized animals. Most dendritic spines remained stable over 4 h whereas filopodia (asterisks) underwent rapid turnover. Scale bar, 2 μm. B-C, Percentage of newly formed (B) and eliminated (C) dendritic spines over 4 h. Administration of isoflurane did not alter spine formation and elimination during this time period. D-E, Percentage of newly formed (D) and eliminated (E) dendritic filopodia over 4 h. Isoflurane anesthesia decreased the elimination of filopodia but had no significant effect on the formation of filopodia over 4 h. Percentages were calculated as the number of spines/filopodia formed or eliminated divided by the number of pre-existing spines/filopodia. Each filled circle represents a single animal. Data are presented as mean ± S.D. * P < 0.05.

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