When is adult hippocampal neurogenesis necessary for learning? evidence from animal research.
ABSTRACT The hippocampus is a key brain structure involved in the short- and long-term processing of declarative memory. Since adult hippocampal neurogenesis was first found, numerous studies have tried to establish the contribution of newborn neurons to hippocampus-dependent cognitive functions. However, this large amount of research has generated contradictory results. In this paper, we review the body of evidence investigating the relationship between hippocampal neurogenesis and learning to conclude the functional role of adult-born hippocampal neurons. First, factors that could explain discrepancies among experiments are taken into account. Then, in addition to methodological differences, we emphasize the importance of the age of the newborn neurons studied, as to how their maturation influences both their properties and potential functionality. Next, we discuss which declarative memory components could require involvement of adult hippocampal neurogenesis, taking into consideration the representational demands of the task, its difficulty and the level of performance reached by the subject. Finally, other factors that could modulate neurogenesis and memory, such as stress levels or previous experience of the animal, should also be taken into consideration in interpreting experiments focused on neurogenesis. In conclusion, our analysis of published studies suggests that new adult-born neurons, under certain circumstances, have a crucial and irreplaceable role in hippocampal learning.
- [Show abstract] [Hide abstract]
ABSTRACT: We investigated whether voluntary exercise prevents the deleterious effects of chronic stress on episodic-like memory and adult hippocampal neurogenesis. After bromodeoxyuridine (BrdU) administration, mice were assigned to receive standard housing, chronic intermittent restraint stress, voluntary exercise or a combination of both (stress starting on the seventh day of exercise). Twenty-four days later, mice were tested in a 'what-when-where' object recognition memory task. Adult hippocampal neurogenesis (proliferation, differentiation, survival and apoptosis) and c-Fos expression in the hippocampus and extra-hippocampal areas (medial prefrontal cortex, amygdala, paraventricular hypothalamic nucleus, accumbens and perirhinal cortex) were assessed after behavior. Chronic intermittent restraint stress impaired neurogenesis and the 'when' memory, while exercise promoted neurogenesis and improved the 'where' memory. The 'when' and 'where' memories correlated with c-Fos expression in CA1 and the dentate gyrus, respectively. Furthermore, analysis suggested that each treatment induced a distinct pattern of functional connectivity among the areas analyzed for c-Fos. In the animals in which stress and exercise were combined, stress notably reduced the amount of voluntary exercise performed. Nevertheless, exercise still improved memory and counteracted the stress induced-deficits in neurogenesis and behavior. Interestingly, compared with the other three treatments, the stressed exercising animals showed a larger increase in cell survival, the maturation of new neurons and apoptosis in the dentate gyrus, with a considerable increase in the number of 24-day-old BrdU+ cells that differentiated into mature neurons. The interaction between exercise and stress in enhancing the number of adult-born hippocampal neurons supports a role of exercise-induced neurogenesis in stressful conditions. Object recognition; Episodic-like memory; Adult hippocampal neurogenesis; Intermittent restraint stress; c-Fos; Functional networks.Neurobiology of Learning and Memory 12/2013; · 3.33 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Aims The aim of the present study was to investigate the effect of swimming exercise on elevated plus-maze (EPM)-associated memory deficit induced by intra-CA1 injection of scopolamine (a muscarinic acetylcholine receptor antagonist used to model Alzheimer’s disease in rodents) in male mice. In addition, involvement of the mu opioid receptors in this phenomenon was investigated. Main Methods Bilateral guide cannulae were implanted to allow intra-CA1 microinjections. Key findings Data showed that mice with 10 and 20 days of swimming, only acquired the emotional memory, while 30 days of swimming exercise improved it. On the other hand, pretest intra-CA1 injection of scopolamine at the doses of 2 and 3 but not 1 μg/mouse reduced the emotional memory. Our results demonstrated that 20 days of swimming by itself and without any drug injection restored the emotional memory deficit induced by intra-CA1 injection of scopolamine, only at the dose of 2 but not 3 μg/mouse. Moreover, once daily injection of the subthreshold doses of morphine (2.5 and 5 mg/kg, i.p.) during the last 7 days of the 20 day-swimming intervention, improved the emotional memory deficit induced by scopolamine (3 μg/mouse) and this effect could be blocked by the subthreshold doses of naloxone (0.2 and 0.4 mg/kg). It was noted that all previous interventions did not alter the anxiety-like behaviors. Significance Swimming improved the emotional memory by itself and restored the emotional memory deficit induced by the intra-CA1 injection of scopolamine. Mu opioid receptor-dependent mechanism(s) is(are) suggested to play a role in this phenomenon.Physiology & Behavior 01/2014; · 3.16 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma. (JINS, 2014, 1, 1-13).Journal of the International Neuropsychological Society 01/2014; · 2.70 Impact Factor