Biology subjects

Laham, B. J.

Publications and source records attributed to Laham, B. J..

3 recordsLinked to original sources

bioRxiv2023

Retrieval of developmental social memories requires activation of the adult-born granule cell-CA2 circuit in mice

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, and this ability returned after new neurons were regenerated. Chemogenetic inhibition of projections from abGCs to the CA2 also temporarily prevented the retrieval of remote mother memories. These findings were observed when abGCs were inhibited at 4-6 weeks old, but not when they were inhibited at 10-12 weeks old. We also found that abGCs are necessary for differentiating features of CA2 network activity, including theta-gamma coupling and sharp wave-ripples, in response to novel versus familiar social stimuli. Taken together, these findings suggest that abGCs are necessary for neuronal oscillations associated with discriminating between social stimuli, thus enabling retrieval of remote developmental memories of the mother by their adult offspring.

neuroscience↗

bioRxiv2022

The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling

Early-life adversity (ELA) predisposes individuals to develop neuropsychiatric conditions, which are more prevalent in women than men. Efforts to model this sex difference in rodents have produced mixed results, with some studies paradoxically showing stronger phenotypes in males than females. Since changes in reproductive hormone levels can increase the likelihood of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when the ratio of progesterone to estrogen is relatively high, ELA mice exhibit increased avoidance behavior, altered activity levels in specific contexts, and increased theta oscillation power in the ventral hippocampus. Ovariectomy, which eliminates circulating estrogen but not progesterone, unexpectedly preserved some of the effects present in diestrus ELA mice. Progesterone receptor antagonism in diestrus normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of the progesterone metabolite allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice

neuroscience↗

bioRxiv2019

Neuroprogesterone synthesis in hypothalamic astrocytes is associated with a pubertal increase in membrane ERα levels

The development of estrogen positive feedback is a hallmark of female puberty. Both estrogen and progesterone signaling are required for the functioning of this neuroendocrine feedback loop but the physiological changes that underlie the emergence of positive feedback remain unknown. Only after puberty does estradiol (E2) facilitate progesterone synthesis in the rat female hypothalamus (neuroP), an event critical for positive feedback and the LH surge. We hypothesize that prior to puberty, these astrocytes have low levels of membrane estrogen receptor alpha (ER), which is needed for facilitation of neuroP synthesis. Thus, we hypothesized that prepubertal astrocytes are unable to respond to E2 with increased neuroP synthesis due a lack of membrane ER. To test this, hypothalamic tissues and enriched primary hypothalamic astrocyte cultures were acquired from pre-pubertal (postnatal week 3) and post- pubertal (week 8) female mice. E2-facilitated progesterone was measured in the hypothalamus pre- and post-puberty, and hypothalamic astrocyte responses were measured after treatment with E2. Prior to puberty, E2-facilitated progesterone synthesis did not occur in the hypothalamus, and mER expression was low in hypothalamic astrocytes, but E2-facilitated progesterone synthesis in the rostral hypothalamus and mER expression increased post- puberty. The increase in mER expression in hypothalamic astrocytes corresponded with an increase in caveolin-1 protein, PKA phosphorylation, and a more rapid [Ca2+]i flux in response to E2. Together, results from the present study indicate that E2-facilitated neuroP synthesis occurs in the rostral hypothalamus, develops during puberty, and corresponds to a post-pubertal increase in mER levels in hypothalamic astrocytes. SIGNIFICANCE STATEMENTEstradiol facilitation of hypothalamic neuroprogesterone synthesis is necessary for the positive feedback of the LH surge. The present study localized the increase of neuroprogesterone to the rostral hypothalamus, a region that mediates estrogen positive feedback. Across pubertal development, hypothalamic astrocytes increase levels of membrane ER and the cell signaling responses needed to facilitate neuroprogesterone synthesis that triggers the LH surge demonstrating a mechanism for pubertal maturation resulting in reproductive competence.

neuroscience↗