Sexual Experience Promotes Adult Neurogenesis in the Hippocampus Despite an Initial Elevation in Stress Hormones

Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute) or once daily for 14 consecutive days (chronic) and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated glucocorticoids but actually promotes neuronal growth and reduces anxiety

Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus): Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus). California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1) biparental care: mate pairs remained with their offspring until weaning; or (2) paternal deprivation (PD): paternal males were permanently removed from their home cage on postnatal day (PND) 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stresscoping behaviors (i.e., percent time spent immobile) during the forced swim task—an effect that was also not sex-dependent. Together, these findings demonstrate that, in a species where paternal care is not only important for offspring survival, PD can also contribute to altered structural and functional neuroplasticity of the hippocampus. The mechanisms contributing to the observed sex-dependent alterations in new cell survival in the dentate gyrus should be further investigated

Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus): Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus). California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1) biparental care: mate pairs remained with their offspring until weaning; or (2) paternal deprivation (PD): paternal males were permanently removed from their home cage on postnatal day (PND) 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile) during the forced swim task—an effect that was also not sex-dependent. Together, these findings demonstrate that, in a species where paternal care is not only important for offspring survival, PD can also contribute to altered structural and functional neuroplasticity of the hippocampus. The mechanisms contributing to the observed sex-dependent alterations in new cell survival in the dentate gyrus should be further investigated

Separation increases passive stress-coping behaviors during forced swim and alters hippocampal dendritic morphology in California mice.

Individuals within monogamous species form bonds that may buffer against the negative effects of stress on physiology and behavior. In some species, involuntary termination of the mother-offspring bond results in increased symptoms of negative affect in the mother, suggesting that the parent-offspring bond may be equally as important as the pair bond. To our knowledge, the extent to which affect in paternal rodents is altered by involuntary termination of the father-offspring bond is currently unknown. Here, we investigated to what extent separation and paternal experience alters passive stress-coping behaviors and dendritic morphology in hippocampal subfields of California mice (Peromyscus californicus). Irrespective of paternal experience, separated mice displayed shorter latencies to the first bout of immobility, longer durations of immobility, and more bouts of immobility than control (non-separated) mice. This effect of separation was exacerbated by paternal experience in some measures of behavioral despair-separation from offspring further decreased the latency to immobility and increased bouts of immobility. In the dentate gyrus, separation reduced dendritic spine density regardless of paternal experience. Increased spine density was observed on CA1 basal, but not apical, dendrites following paternal experience. Regardless of offspring presence, fatherhood was associated with reduced apical dendritic spine density in area CA3 of the hippocampus. Separation enhanced complexity of both basal and apical dendrites in CA1, while fatherhood reduced dendritic complexity in this region. Our data suggest that forced dissolution of the pair bond induces passive stress-coping behaviors and contributes to region-specific alterations in hippocampal structure in California mouse males

Separation and fatherhood have hippocampal subfield-specific effects on dendritic spine density in California mouse fathers.

<p>(A) Separation from mate and/or offspring decreases dendritic spine density of dentate gyrus (DG) granule cells, compared to control males. *p ≤ 0.05. (B) Neither paternal experience nor separation alters dendritic spine density of CA1 apical pyramidal cells. (C) Paternal experience increases spine density on CA1 basal dendrites, but (D) decreases spine density of CA3 apical dendrites ⁺p ≤ 0.05, non-fathers compared to fathers, ^&p ≤ 0.001, non-fathers compared to fathers. (E) Neither paternal experience nor separation alters dendritic spine density of CA3 basal pyramidal cells. Bars represent Mean + SEM.</p

Separation and paternal experience alter dendritic tree complexity in CA1, but not DG or CA3, of the hippocampus in California mice.

<p>Separation and paternal experience alter dendritic tree complexity in CA1, but not DG or CA3, of the hippocampus in California mice.</p

Separation increases passive stress-coping behavior during the forced swim task in male California mice.

<p>(A) Twenty days of separation, regardless of paternal experience, significantly shortens the latency to the initial bout of immobility during the forced swim task, compared to non-separated controls. Among paternal mice, separation from offspring exacerbates this effect, as separated fathers have a shorter latency to immobility than non-separated fathers. (B) Regardless of paternal experience, 20 days of separation increases the duration of immobility during the forced swim task. (C) Twenty days of separation, regardless of paternal experience, increases bouts of immobility during the forced swim task, compared to non-separated controls. Among paternal mice, separation from offspring exacerbates this effect as separated fathers have more bouts of immobility than non-separated fathers. *p ≤ 0.05, ^#p ≤ 0.01, ^&p ≤ 0.001. Bars represent mean + SEM.</p

Microlucida tracings of Golgi-impregnated CA1 pyramidal cells.

<p>Representative tracings of a (A) control non-father, (B) control father, (C) separated non-father, and (D) separated father. Scale bar = 200 μm.</p