Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Abstract

Learning increases the survival of new cells that are generated in the hippocampal formation before the training experience, especially if the animal learns to associate stimuli across time [Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Nat Neurosci 2:260 -265]. All relevant studies have been conducted on male rats, despite evidence for sex differences in this type of learning. In the present study, we asked whether sex differences in learning influence the survival of neurons generated in the adult hippocampus. Male and female adult rats were injected with one dose of bromodeoxyuridine (BrdU; 200 mg/kg), to label one population of dividing cells. One week later, half of the animals were trained with a temporal learning task of trace eyeblink conditioning, while the other half were not trained. Animals were killed 1 day after training (12 days after the BrdU injection). Hippocampal tissue was stained for BrdU and a marker of immature neurons, doublecortin. Both sexes learned to emit the conditioned eyeblink response during the trace interval. As a consequence, more new neurons remained in their hippocampi than in sex-matched controls. In individual animals, the number of surviving cells correlated positively with asymptotic performance; those that expressed more learned responses retained more new neurons. However, animals that learned very well retained even more new cells if they required many trials to do so. Because females emitted more learned responses than males did, they retained nearly twice as many new cells per unit volume of tissue. This effect was most evident in the ventral region of the hippocampal formation. Thus, sex differences in learning alter the anatomical structure of the hippocampus. As a result, male and female brains continue to differentiate in adulthood.eyeblink conditioning ͉ learning ͉ neurogenesis ͉ sex differences ͉ stem cell

Stress and estrous cycle affect strategy but not performance of female C57BL/6J mice

“…Tasks that require a functional hippocampus such as trace eyeblink conditioning showed improved learning during the proestrus [25][26][27], while studies using spatial learning tasks, reported impairments in learning during the proestrus phase on the radial arm maze [28] or during the estrus phase in the Morris water maze [29,30]. We detected no effect of the estrous cycle phase on the learning of the CHB in mice.…”

17β-Estradiol Increases Astrocytic Vascular Endothelial Growth Factor (VEGF) in Adult Female Rat Hippocampus

“…The results have functional implications because of the known effects of estrogens and VEGF in hippocampus, such as stimulation of postnatal neurogenesis in the dentate gyrus (16,18,43). The results of the present study suggest that the effects of estrogens on neurogenesis may be mediated, at least in part, by their ability to increase VEGF in the neurogenic niche.…”

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…It was found that associative learning increases the survival of new neurons in the adult hippocampus, regardless of temporal contiguity (Leuner et al 2006). Cell survival was later shown to be regulated by the acquisition and not memory expression (Anderson et al 2011), the sex of the animals (Dalla et al 2009), and the degree of task difficulty. Indeed, establishing a contextual conditioned stimulus representation acquired in a single training trial is not sufficient to change the survival of cells born 10 d before exposure to the task (Pham et al 2005).…”