Lasting adaptations in social behavior produced by social disruption and inhibition of adult neurogenesis

Rats from disrupted hierarchies exhibit a preference for familiar over novel rats while resting.

“Although control rats and rats from stable hierarchies prefer novel over familiar rats while resting, rats from disrupted hierarchies exhibit the converse preference of familiar over novel rats.”

• Also stated in: § Abstract · plain

  “Social disruption produced a preference for familiar over novel conspecifics”

Oxytocin treatment immediately after social disruption had no effect on anxiety-like behavior in disrupted rats.

“We found that this manipulation had no effect on anxiety-like behavior but prevented the social preference for familiar conspecifics.”

Oxytocin treatment immediately after social disruption prevented the social preference for familiar conspecifics in disrupted rats.

“We found that this manipulation had no effect on anxiety-like behavior but prevented the social preference for familiar conspecifics.”

• Also stated in: § Abstract · plain

  “Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels.”

Rats from disrupted hierarchies displayed reduced anxiety-like behavior.

“Despite suppressed neurogenesis, rats from disrupted hierarchies displayed reduced anxiety-like behavior without global cognitive deficits.”

Differences between dominants and subordinates in adult neurogenesis were eliminated when the hierarchy was disrupted.

“We found that differences between dominants and subordinates in adult neurogenesis were eliminated when the hierarchy was disrupted.”

Reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-TK rats resulted in social behavior similar to disrupted rats.

“Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats.”

GFAP-TK rats with reduced new neuron number without social disruption experience had control levels of anxiety-like behavior.

“these rats had control levels of anxiety-like behavior but social resting preference for familiar conspecifics.”

Rats from disrupted hierarchies did not have global cognitive deficits.

“Despite suppressed neurogenesis, rats from disrupted hierarchies displayed reduced anxiety-like behavior without global cognitive deficits.”

Control rats and rats from stable hierarchies prefer novel over familiar rats while resting.

“Although control rats and rats from stable hierarchies prefer novel over familiar rats while resting, rats from disrupted hierarchies exhibit the converse preference of familiar over novel rats.”

New neuron production in the hippocampus was consistently lower after social disruption.

“We further found that new neuron production in the hippocampus was consistently lower after social disruption.”

• Also stated in: § Abstract · plain

  “Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies.”

GFAP-TK rats with reduced new neuron number without social disruption experience showed social resting preference for familiar conspecifics.

“these rats had control levels of anxiety-like behavior but social resting preference for familiar conspecifics.”

Switched dominants showed a significant decrease in dominance score from 5.7 ± 1.6 to 0.2 ± 1.5.

“Switched dominants showed a significant decrease in dominance score (aggressive acts Ϫ defensive acts) from 5.7 Ϯ 1.6 to 0.2 Ϯ 1.5 [two-way repeated-measures ANOVA, interaction of phase (before switch vs after switch), and dominance score, F (1,38) ϭ 10.294, p ϭ 0.003].”

In every instance, switching dominants led to a loss of dominant status for these animals.

“In every instance, switching dominants led to a loss of dominant status for these animals.”

In stable cohorts, aggression did not change from day 3 to 6.

“In stable cohorts, aggression did not change from day 3 to 6 (3.87 Ϯ 0.56 vs 4.09 Ϯ 0.60 acts/rat, t (8) ϭ Ϫ0.27, p ϭ 0.821)”

Throughout the 6 d period of living in the VBS, the overall level of aggression changed significantly.

“Throughout the 6 d period of living in the VBS, the overall level of aggression changed significantly (F (2,14) ϭ 12.97, p ϭ 0.001; Fig. 1C).”

In disrupted cohorts, after the dominant rats were switched between two hierarchies, the level of aggression increased significantly from day 3 to 6.

“but in disrupted cohorts, after the dominant rats were switched between two hierarchies, the level of aggression increased significantly from day 3 to 6 ( p ϭ 0.001; Fig. 1C).”

Hierarchy disruption led to a reorganization of the social hierarchy with no evidence of a clear dominant.

“as well as to a reorganization of the social hierarchy with no evidence of a clear dominant”

Postdisruption aggression levels were significantly higher than day 1 aggression levels.

“Postdisruption aggression levels were also significantly higher than day 1 aggression levels ( p ϭ 0.0001; Fig. 1C).”

Between days 1 and 3, the level of aggression decreased for both stable and disrupted groups.

“Between days 1 and 3, the level of aggression decreased for both groups (stable and disrupted; p ϭ 0.005).”

No changes were observed on any of these measures in the dorsal DG.

“In addition, no changes were observed on any of these measures in the dorsal DG ( p Ͼ 0.05 for all such comparisons).”

More than 80% of IdU+ and CldU+ cells colabeled with the immature neuronal marker DCX.

“More than 80% of IdU ϩ and CldU ϩ cells colabeled with the immature neuronal marker DCX.”

Social disruption decreased the number of new cells in the ventral DG labeled before the disruption (IdU) and after the disruption (CldU) compared with controls at the 2 week time point.

“Social disruption also decreased the number of new cells in the ventral DG labeled before the disruption (IdU, t (21) ϭ 4.31, p ϭ 0.002), as well as the number of new cells in the ventral DG labeled after the disruption (CldU, t (22) ϭ 4.32, p ϭ 0.001) compared with controls at the 2 week time point (Fig. 1 D, F ).”

The number of Sox2+ cells and GFAP+ cells with radial morphology were decreased in the ventral DG after social disruption compared with control at 2 weeks.

“The number of Sox2 ϩ cells (t (6) ϭ Ϫ2.68, pϭ0.037) and GFAP ϩ cells with radial morphology (t (6) ϭ Ϫ3.73, pϭ0.01) were decreased in the ventral DG after social disruption compared with control (Fig. 1 E, F ).”

No differences were observed in the numbers of IdU+ or CldU+ cells in the SVZ.

“No differences were observed in the numbers of IdU ϩ or CldU ϩ cells in the SVZ, suggesting that these effects may have been specific to the hippocampus ( p Ͼ 0.05 for all comparisons).”

Social disruption produced a decrease in the numbers of neuronal precursor cells and immature neurons compared with control groups at the 2 week time point.

“Social disruption produced a decrease in the numbers of neuronal precursor cells and immature neurons compared with control groups at the 2 week time point.”

Dominants in a stable hierarchy had more new neurons in the ventral DG than subordinates.

“Consistent with previous results (Kozorovitskiy and Gould, 2004), we found that dominants in a stable hierarchy had more new neurons in the ventral DG than subordinates (IdU, 6552 Ϯ 840 in dominants vs 4448 Ϯ 480 in subordinates, t (13) ϭ 2.41; p ϭ 0.032).”

• cites Kozorovitskiy and Gould, 2004Not checked yet

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Social disruption eliminated the advantage of being dominant in dominants, so that dominants and subordinates in disrupted groups did not differ in new neurons.

“However, social disruption eliminated the advantage of being dominant in dominants (IdU, 3300 Ϯ 607 in dominants vs 2762 Ϯ 218 in subordinates, t (13) ϭ Ϫ1.07, pϭ0.3).”

Social disruption produced a decrease in the number of immature neurons (DCX+) in the ventral DG compared with controls at the 2 week time point.

“Social disruption also produced a decrease in the number of immature neurons (labeled with DCX) in the ventral DG compared with controls at the 2 week time point (t (6) ϭ 3.07, p ϭ 0.022; Fig. 1 E, F ).”

The suppressive effects of social disruption on DCX+ cells were not seen in the dorsal DG.

“Similar to what was observed for neuronal precursors, the suppressive effects of social disruption on DCX ϩ cells were not seen in the dorsal DG ( p ϭ 0.21).”

Rats preferred to investigate a novel rat over a familiar rat, regardless of whether they had been treated with oxytocin.

“Likewise, rats preferred to investigate a novel rat over a familiar rat, regardless of whether they had been treated with oxytocin (two-way ANOVA of condition vs novelty; main effect of novelty, F (1,13) ϭ 6.59, p ϭ 0.028).”

Rats from a disrupted hierarchy that received vehicle injections displayed a preference for resting near a familiar, as opposed to novel, rat.

“As previously observed for socially disrupted rats (Fig. 2B), rats from a disrupted hierarchy that received vehicle injections displayed a preference for resting near a familiar, as opposed to novel, rat (Fig. 3C).”

Control rats often initiated a movement path toward the familiar rat but hesitated and turned back to rest by the novel rat, suggesting VTE-like behavior.

“We further analyzed the behavior of rats after investigation of the novel rat and found that control rats often initiated a movement path toward the opposite side of the social chamber, in the direction of the familiar rat, but hesitated and turned back to rest by the novel rat, suggesting a behavior similar to what has been described as reflecting VTE in maze studies (Redish, 2016).”

• cites Redish, 2016Not checked yet

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At the 6 week time point, there were no significant differences between control and disrupted groups in the dorsal DG for any measure.

“At the 6 week time point, there were no significant differences between control and disrupted groups in the dorsal DG for any measure ( p Ͼ 0.05).”

This preference was reversed in socially disrupted rats with oxytocin treatment.

“This preference was reversed in socially disrupted rats with oxytocin treatment (Fig. 3C).”

Rearing and grooming behavior did not vary between control and disrupted groups in either duration or side preference.

“After addition of conspecifics to the chamber, rearing and grooming behavior, sometimes used as measures of anxiety (Daniels et al., 2008), did not vary between control and disrupted groups in either duration of these behaviors or side preference (Fig. 2 E, F; p Ͼ 0.05 for all comparisons).”

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Disrupted rats had a greater propensity to cross the chamber to rest near a familiar rat after investigation of the novel rat.

“That is, disrupted rats had a greater propensity to cross the chamber to rest near a familiar rat after investigation of the novel rat (Fig. 2C).”

Preference for resting near objects located in novel versus familiar locations was not detected in either group.

“Preference for resting near objects located in novel versus familiar locations was not detected in either group.”

No differences were observed in behavior during habituation to the social chamber, including center crossing and active time.

“These results appear independent of general anxiety measures within the social preference apparatus, because we did not observe differences in behavior during habituation to the social chamber (in the absence of conspecifics), including center crossing and active time (Fig. 2D).”

There were no differences in V1aR expression in dorsal or ventral DG between disrupted and control groups.

“There were no differences in V1aR expression in dorsal or ventral DG between disrupted and control groups ( p Ͼ 0.05 for both comparisons).”

Four weeks after the end of oxytocin treatment, oxytocin-treated rats did not show any difference in anxiety-like behavior in the elevated plus maze compared with vehicle-treated rats.

“Four weeks after the end of oxytocin treatment, oxytocin-treated rats did not show any difference in anxiety-like behavior in the elevated plus maze compared with vehicle-treated rats (proportional time in open arms, 0.21 Ϯ 0.06 in disrupted ϩ vehicle vs 0.17 Ϯ 0.06 in disrupted ϩ oxytocin; t (14) ϭ 0.44, pϭ0.66).”

Compared with controls, disrupted rats exhibited fewer instances of VTE-like behavior after investigating the novel stimulus rat but not the familiar stimulus rat.

“Thus, compared with controls, disrupted rats exhibited fewer instances of VTE-like behavior after investigating the novel stimulus rat but not the familiar stimulus rat (see Fig. 5; social disruption group ϫ stimulus rat interaction, F (1,16) ϭ 8.67, p ϭ 0.001).”

Control rats preferred to rest near the novel rat after investigation of the novel rat.

“In contrast, control rats preferred to rest near the novel rat after investigation of the novel rat (proportional crosses to familiar after investigating novel, t (9) ϭ 4.24, p ϭ 0.002; Fig. 2C).”

Plasma testosterone levels did not differ significantly between control and disrupted groups.

“Plasma testosterone levels did not differ significantly between groups (106.1 Ϯ 27 ng/ml in control, 243.4 Ϯ 88.8 ng/ml in disrupted; p Ͼ 0.05).”

The proportion of Ki67+ cells that expressed OTR or V1aR did not differ between groups in dorsal or ventral DG.

“OTR and V1aR expression was observed on Ki67 ϩ proliferating cells in the DG, but the proportion of Ki67 ϩ cells that expressed either of these receptors did not differ between groups in dorsal or ventral DG ( p Ͼ 0.05 for all comparisons; Fig. 1G).”

Social disruption resulted in decreased baseline CORT levels.

“Instead, social disruption resulted in decreased baseline CORT levels (102 Ϯ 36.1 ng/ml in control, 31.96Ϯ 22.5 ng/ml in disrupted; t (12) ϭ 1.96, p ϭ 0.036).”

Performance on the object location task did not differ between rats from disrupted hierarchies and rats from standard group housing.

“Performance on the object location task did not differ between rats from disrupted hierarchies and rats from standard group housing (discrimination ratio, t (12) ϭ 0.21, p Ͼ 0.05; Fig. 1H ).”

Rats in both groups emitted 50 kHz vocalizations.

“Instead, rats in both groups emitted 50 kHz vocalizations, which are typically associated with neutral or rewarding stimuli (Brudzynski, 2013).”

• cites Brudzynski, 2013Not checked yet

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There were no differences in the percentage of IdU- or CldU-labeled cells that expressed DCX among any of the groups examined.

“There were no differences in the percentage of IdU-or CldU-labeled cells that expressed DCX among any of the groups examined ( p Ͼ 0.05), suggesting that the changes in IdU-or CldU-labeled cell number associated with disruption represent suppressed adult neurogenesis.”

Rats from a disrupted VBS exhibit lower levels of plasma CORT than rats from stable hierarchies and control conditions.

“However, somewhat paradoxically, rats from a disrupted VBS exhibit lower levels of plasma CORT than rats from stable hierarchies and control conditions.”

When tested behaviorally 6 weeks after the last GCV treatment, no significant differences were observed between GCV- and vehicle-treated TK rats on object location.

“When tested behaviorally 6 weeks after the last GCV treatment, no significant differences were observed between GCV-and vehicle-treated TK rats on object location (0.22 Ϯ 0.19 for TK ϩ vehicle vs 0.36 Ϯ 0.31 for TK ϩ GCV; t (17) ϭ 1.21, p ϭ 0.2).”

GCV treatment also decreased the number of BrdU-labeled cells in the SVZ.

“GCV treatment also decreased the number of BrdU-labeled cells in the SVZ from 3704 Ϯ 240 to 2436 Ϯ 180 (t (6) ϭ Ϫ4.28, p ϭ 0.008).”

The reduction in the number of new neurons with social disruption was observed regardless of dominance position.

“The reduction in the number of new neurons with social disruption was observed regardless of dominance position and may have occurred as a result of the stressful effects of persistent aggression (Cze ´h et al., 2002).”

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Social recognition did not differ between vehicle- and GCV-treated rats.

“In addition, social recognition did not differ between vehicle-and GCV-treated rats (two-way ANOVA of condition vs novelty; main effect of novelty, F (1,15) ϭ 6.51, p ϭ 0.03).”

Rats that received oxytocin lost their preference for familiarity, changing strategy to rest near the novel, as opposed to the familiar, rat.

“Rats that received oxytocin lost their preference for familiarity, changing strategy to rest near the novel, as opposed to the familiar, rat (t (30) ϭ 3.13, p ϭ 0.003), similar to what was observed in naive rats without social disruption (compare with Fig. 2B).”

Socially disrupted rats appeared to be less anxious than control rats on the elevated plus maze.

“In fact, socially disrupted rats appeared to be less anxious than control rats on the elevated plus maze.”

V1aR staining is not changed in the ventral dentate gyrus in rats from a disrupted hierarchy.

“OTR staining, but not V1aR staining, is increased in the ventral DG in rats from a disrupted hierarchy, but no changes were observed in the number of cells colabeled for Ki67 and OTR or Ki67 and V1aR.”

Disrupting a dominance hierarchy by switching dominants on day 4 produces an increase in aggression.

“Individual aggressive acts decrease by day 3 in a VBS, but disrupting a hierarchy by switching dominants on day 4 produces an increase in aggression.”

IdU+ and CldU+ cells in the ventral dentate gyrus are decreased in number in rats from a disrupted hierarchy.

“IdU ϩ and CldU ϩ cells in the ventral DG are decreased in number in rats from a disrupted hierarchy.”

In a visible burrow system (VBS), individual aggressive acts decrease by day 3.

“Individual aggressive acts decrease by day 3 in a VBS, but disrupting a hierarchy by switching dominants on day 4 produces an increase in aggression.”

Sox2+, radial GFAP+ (rGFAP+), and DCX+ cells in the ventral dentate gyrus are decreased in number in rats from a disrupted hierarchy.

“Sox2 ϩ , radial GFAP ϩ (rGFAP ϩ ), and DCX ϩ cells in the ventral DG are decreased in number in rats from a disrupted hierarchy.”

There were no differences between rats from a disrupted hierarchy and controls in object location memory performance.

“There were no differences in rats' object location memory performance, because both groups investigate an object in a novel location more than an object in a familiar location.”

OTR staining is increased in the ventral dentate gyrus in rats from a disrupted hierarchy.

“OTR staining, but not V1aR staining, is increased in the ventral DG in rats from a disrupted hierarchy, but no changes were observed in the number of cells colabeled for Ki67 and OTR or Ki67 and V1aR.”

Neither group showed a preference for resting near objects located in novel or familiar locations.

“Neither group showed a preference for resting near objects located in novel or familiar locations.”

Rats from a disrupted hierarchy spent more time in the open arms of an elevated plus maze than controls, in terms of both absolute time and proportion of entries in the open arms.

“Rats from disrupted hierarchy spent more time in the open arms of an elevated plus maze than controls, in terms of both absolute time and proportion of entries in the open arms.”

After investigation of the novel rat, rats from a disrupted hierarchy prefer to cross the chamber to rest near the familiar rat.

“Differences in social preference are driven by behaviors after investigation of the novel rat: rats from a disrupted hierarchy prefer to cross the chamber to rest near the familiar rat, whereas both groups show similar resting behaviors after investigation of the familiar rat.”

GFAP-TK rats with a suppressed pool of 6-week-old neurons show no impairments in recognizing a novel rat.

“GFAP-TK rats with a suppressed pool of 6-week-old neurons show no impairments to recognizing a novel rat but exhibit a resting preference for a familiar rat.”

Rats treated with oxytocin after social disruption prefer to rest near the novel rat.

“Social recognition is not affected by OT administration after social disruption, whereas rats treated with OT prefer to rest near the novel rat.”

• Also stated in: § Discussion · plain

  “Oxytocin treatment after social disruption increases the number of immature neurons in the ventral DG and restores a resting preference for novelty.”

Social recognition is not affected by oxytocin administration after social disruption.

“Social recognition is not affected by OT administration after social disruption, whereas rats treated with OT prefer to rest near the novel rat.”

Oxytocin-treated rats are more likely to rest near the novel rat after investigation of either side.

“OT-treated rats are more likely to rest near the novel rat after investigation of either side.”

Rats from a disrupted hierarchy prefer to rest near a familiar rat.

“Whereas rats from standard group housing showed a preference for resting near a novel rat, rats from a disrupted hierarchy prefer to rest near a familiar rat.”

Rats treated with oxytocin after social disruption showed an increase in immature neurons in the ventral dentate gyrus.

“Rats treated with OT after social disruption showed an increase in immature neurons in the ventral DG.”

• Also stated in: § Discussion · plain

  “Oxytocin treatment after social disruption increases the number of immature neurons in the ventral DG and restores a resting preference for novelty.”

Both control and disrupted groups show similar resting behaviors after investigation of the familiar rat.

“Differences in social preference are driven by behaviors after investigation of the novel rat: rats from a disrupted hierarchy prefer to cross the chamber to rest near the familiar rat, whereas both groups show similar resting behaviors after investigation of the familiar rat.”

Social disruption produces no deficits in the ability to recognize a familiar conspecific.

“Social disruption produces no deficits in the ability to recognize a familiar conspecific, because both control and disrupted groups investigate a novel rat more than a familiar rat.”

There were no group differences in side localization or duration of grooming behavior.

“There were no group differences in side localization or duration of grooming behavior.”

There were no group differences in side localization or duration of rearing behavior.

“There were no group differences in side localization or duration of rearing behavior.”

Before the addition of stimulus rats, the groups exhibited the same amount of activity, in terms of both center crossings and time spent mobile in the chamber.

“Before the addition of stimulus rats, groups exhibited the same amount of activity, in terms of both center crossings and time spent mobile in the chamber.”

No rats emitted 22 kHz USVs during the social test.

“No rats emitted 22 kHz USVs during the social test.”

GFAP-TK rats with a suppressed pool of 6-week-old neurons exhibit a resting preference for a familiar rat.

“GFAP-TK rats with a suppressed pool of 6-week-old neurons show no impairments to recognizing a novel rat but exhibit a resting preference for a familiar rat.”

• Also stated in: § Discussion · plain

  “GFAP-TK rats treated with GCV show a suppression in adult neurogenesis in the DG and exhibit a resting preference for a familiar rat.”

Rats from standard group housing show a preference for resting near a novel rat.

“Whereas rats from standard group housing showed a preference for resting near a novel rat, rats from a disrupted hierarchy prefer to rest near a familiar rat.”

GFAP-TK rats treated with GCV showed a suppression in BrdU+ neurons in the dentate gyrus.

“GFAP-TK rats treated with GCV showed a suppression in BrdU ϩ neurons in the DG.”

• Also stated in: § Discussion · plain

  “GFAP-TK rats treated with GCV show a suppression in adult neurogenesis in the DG and exhibit a resting preference for a familiar rat.”

No significant changes were observed in post-familiar VTE-like behavior in any group.

“No significant changes were observed in post-familiar VTE-like behavior in any group.”

After investigation of the novel rat, disrupted VBS rats and GFAP-TK rats exhibited fewer instances of VTE-like behavior, resulting in fewer turns back to the novel side, than controls.

“After investigation of the novel rat, disrupted VBS rats and GFAP-TK rats exhibited fewer instances of VTE-like behavior, resulting in fewer turns back to the novel side, than controls.”

GFAP-TK rats with a suppressed pool of 6-week-old neurons prefer to rest near the familiar rat after investigation of either side.

“GFAP-TK rats with a suppressed pool of 6-week-old neurons prefer to rest near the familiar rat after investigation of either side.”

Oxytocin treatment reversed the effects of social disruption on VTE-like behavior so that the values were similar to socially naive controls.

“Oxytocin treatment reversed the effects of social disruption on VTE-like behavior so that the values were similar to socially naive controls.”

Changes related to dominance hierarchy destabilization could have important behavioral consequences.

“it is likely that changes related to dominance hierarchy destabilization could have important behavioral consequences.”

Dominant rats in a stable hierarchy in the VBS exhibit a higher rate of adult neurogenesis in the hippocampus compared with subordinate rats.

“Dominant rats in a stable hierarchy in the VBS exhibit a higher rate of adult neurogenesis in the hippocampus compared with subordinate rats (Kozorovitskiy and Gould, 2004)”

• cites Kozorovitskiy and Gould, 2004Not checked yet

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Hierarchy destabilization is common in rats, occurring as a result of death, aging, or illness of a dominant rat, a rogue rat joining the group, or a change in habitat conditions.

“Although hierarchy stability can be lasting, destabilization is common, occurring as a result of death, aging, or illness of a dominant rat, a rogue rat joining the group, or a change in habitat conditions (Barnett, 1958).”

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Adult neurogenesis in the hippocampus has been linked to a variety of functions, including anxiety/stress regulation and cognition.

“Because adult neurogenesis in the hippocampus has been linked to a variety of functions, including anxiety/stress regulation and cognition (Dupret et al., 2008;Snyder et al., 2011;Opendak and Gould, 2015)”

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• cites Snyder et al., 2011Not checked yet

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• cites Opendak and Gould, 2015Not checked yet

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Hierarchy disruption led to an increase in aggression that exceeded that of naive rats placed in the VBS for the first time.

“hierarchy disruption led to an increase in aggression that exceeded that of naive rats placed in the VBS for the first time”

Three days is sufficient time for establishing dominance hierarchies among male Sprague Dawley rats.

“Three days is sufficient time for establishing dominance hierarchies among male Sprague Dawley rats (Kozorovitskiy and Gould, 2004).”

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The 6 week time point is sufficient for neurons generated during social experience to become functionally integrated into the existing hippocampal circuitry and affect performance on hippocampus-dependent tasks.

“the second time point was selected because it is sufficient for neurons generated during social experience to become functionally integrated into the existing hippocampal circuitry and affect performance on hippocampus-dependent tasks (Snyder et al., 2009).”

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Suppressed neurogenesis in the hippocampus may play a role in the change in social preference after social disruption.

“and that suppressed neurogenesis in the hippocampus may play a role in this latter outcome.”

• Also stated in: § Abstract · hedged

  “possibly by reducing adult neurogenesis in the hippocampus.”

The effects of social disruption on new cells may have been specific to the hippocampus.

“No differences were observed in the numbers of IdU ϩ or CldU ϩ cells in the SVZ, suggesting that these effects may have been specific to the hippocampus ( p Ͼ 0.05 for all comparisons).”

Living in a VBS, even under stable conditions, did not produce any measurable change in neurogenesis.

“Furthermore, no differences were observed between control and stable VBS cohorts (exclud-ing dominant rats) on any measure of cell proliferation or adult neurogenesis ( p Ͼ 0.05 for all comparisons), suggesting that living in a VBS, even under stable conditions, did not produce any measurable change in neurogenesis.”

Switching location or being housed with a new conspecific did not alter baseline levels of neurogenesis.

“No differences were observed between rats that were pair-housed in standard cages and those that were switched between cages, suggesting that switching location or being housed with a new conspecific did not alter baseline levels of neurogenesis (e.g., for ventral DG IdU, 4824 Ϯ 363 in switched vs 5580 Ϯ 1222 in nonswitched; t (6) ϭ 0.59; p ϭ 0.57).”

The observed decreases after social disruption were in Sox2+/GFAP+ radial glia-like precursor cells.

“No changes were observed in horizontal GFAP ϩ cells ( p ϭ 0.53), the proportion of radial to horizontal cells ( p ϭ 0.23), or the degree of colabeling of Sox2 and GFAP ( p ϭ 0.26) with social disruption, indicating that the observed decreases were in Sox2 ϩ /GFAP ϩ radial glia-like precursor cells.”

Cage controls and subordinates in a stable hierarchy did not differ on measures of adult neurogenesis.

“As shown previously (Kozorovitskiy and Gould, 2004), cage controls and subordinates in a stable hierarchy did not differ on measures of adult neurogenesis.”

• cites Kozorovitskiy and Gould, 2004Not checked yet

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These results appear independent of general anxiety measures within the social preference apparatus.

“These results appear independent of general anxiety measures within the social preference apparatus, because we did not observe differences in behavior during habituation to the social chamber (in the absence of conspecifics), including center crossing and active time (Fig. 2D).”

The changes in IdU- or CldU-labeled cell number associated with disruption represent suppressed adult neurogenesis.

“There were no differences in the percentage of IdU-or CldU-labeled cells that expressed DCX among any of the groups examined ( p Ͼ 0.05), suggesting that the changes in IdU-or CldU-labeled cell number associated with disruption represent suppressed adult neurogenesis.”

No significant differences in baseline CORT levels were observed between GFAP-TK rats treated with GCV and wild-type controls.

“No significant differences in baseline CORT levels were observed between GFAP-TK rats treated with GCV and wild-type controls (158.8Ϯ 39.8 ng/ml in WT, 206.0 Ϯ 34.1 ng/ml in GFAP-TK; t (9) ϭ 0.87, p ϭ 0.41).”

Social disruption suppressed the numbers of progenitor cells and new neurons for all members of a dominance group.

“Social disruption suppressed the numbers of progenitor cells and new neurons for all members of a dominance group.”

Social disruption may fine tune subsequent social behavior, at least in part, by reducing the number of new neurons in the DG.

“These data suggest that social disruption may fine tune subsequent social behavior, at least in part, by reducing the number of new neurons in the DG.”

• AssumptionRests on an assumption: The social disruption paradigm used in this study produces chronic stress in rats.

The lower CORT levels may reflect hypocortisolism, a phenomenon wherein chronic stress downregulates the hypothalamic-pituitary-adrenal axis response.

“This may reflect hypocortisolism, a phenomenon wherein chronic stress downregulates the hypothalamic-pituitary-adrenal axis response (Yehuda et al., 1990;Rohleder et al., 2004).”

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• cites Rohleder et al., 2004Not checked yet

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GCV treatment was effective in reducing adult neurogenesis in GFAP-TK rats, as BrdU+ cells were lower in both the dorsal and ventral DG compared with vehicle-treated GFAP-TK rats.

“GCV treatment was effective in reducing adult neurogenesis in GFAP-TK rats, because BrdU ϩ cells were lower in both the dorsal and ventral DG compared with in GFAP-TK rats treated with vehicle (t (15) ϭ 2.56, p ϭ 0.022 for dorsal DG; t (15) ϭ 3.18, p ϭ 0.006 for ventral DG; Fig. 4B).”

• AssumptionRests on an assumption: The GFAP-TK/GCV manipulation reduces adult neurogenesis specifically, without affecting other cell populations or functions that could explain the behavioral effects.

A similar adult neurogenesis mechanism influences social behavior in social disruption and transgenic inhibition.

“Together with our findings that reduced adult neurogenesis in transgenic socially naive rats mimics the social behavior change we observed with social disruption, these findings suggest that a similar adult neurogenesis mechanism influences social behavior in each case.”

• AssumptionRests on an assumption: The social disruption paradigm used in this study produces chronic stress in rats.
• AssumptionRests on an assumption: The GFAP-TK/GCV manipulation reduces adult neurogenesis specifically, without affecting other cell populations or functions that could explain the behavioral effects.

The increase in hippocampal OTR immunolabeling observed with social disruption may be linked to lower CORT levels.

“The increase in hippocampal OTR immunolabeling we observed with social disruption may be linked to lower CORT levels.”

The lack of effect on object location memory and anxiety-like behavior with reduced adult neurogenesis is consistent with data from naive mice lacking immature neurons.

“The lack of effect on object location memory and anxiety-like behavior with reduced adult neurogenesis is consistent with data from naive mice lacking immature neurons (Garrett et al., 2015;Seo et al., 2015).”

• cites Garrett et al., 2015Not checked yet

  Not checked in the free run.

• cites Seo et al., 2015Not checked yet

  Not checked in the free run.

Suppression in neurogenesis in the DG during adulthood may produce lasting changes in social behavior without causing obvious impairments in hippocampal functions, such as object location memory and anxiety regulation.

“Together, these data suggest that suppression in neurogenesis in the DG during adulthood may produce lasting changes in social behavior without causing obvious impairments in hippocampal functions, such as object location memory and anxiety regulation.”

• AssumptionRests on an assumption: The social disruption paradigm used in this study produces chronic stress in rats.
• AssumptionRests on an assumption: The GFAP-TK/GCV manipulation reduces adult neurogenesis specifically, without affecting other cell populations or functions that could explain the behavioral effects.

VTE behavior in the social preference test changes in groups with suppressed adult neurogenesis.

“VTE behavior in the social preference test changes in groups with suppressed adult neurogenesis.”

Social disruption has a lasting effect on social behavior.

“Social disruption has a lasting effect on social behavior.”

Social disruption suppresses adult neurogenesis.

“Social disruption suppresses adult neurogenesis without impairing performance on hippocampus-dependent tasks.”

Social disruption does not impair performance on hippocampus-dependent tasks.

“Social disruption suppresses adult neurogenesis without impairing performance on hippocampus-dependent tasks.”