Michael Saxe

Bio: Michael Saxe is an academic researcher from Columbia University. The author has contributed to research in topics: Neurogenesis & Hippocampal formation. The author has an hindex of 7, co-authored 8 publications receiving 6150 citations. Previous affiliations of Michael Saxe include Howard Hughes Medical Institute.

Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

Abstract: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

Abstract: Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.

Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment

Abstract: Environmental enrichment increases adult hippocampal neurogenesis and alters hippocampal-dependent behavior in rodents. To investigate a causal link between these two observations, we analyzed the effect of enrichment on spatial learning and anxiety-like behavior while blocking adult hippocampal neurogenesis. We report that environmental enrichment alters behavior in mice regardless of their hippocampal neurogenic capability, providing evidence that the newborn cells do not mediate these effects of enrichment.

Paradoxical influence of hippocampal neurogenesis on working memory.

Abstract: To explore the function of adult hippocampal neurogenesis, we ablated cell proliferation by using two independent and complementary methods: (i) a focal hippocampal irradiation and (ii) an inducible and reversible genetic elimination of neural progenitor cells. Previous studies using these methods found a weakening of contextual fear conditioning but no change in spatial reference memory, suggesting a supportive role for neurogenesis in some, but not all, hippocampal-dependent memory tasks. In the present study, we examined hippocampal-dependent and -independent working memory using different radial maze tasks. Surprisingly, ablating neurogenesis caused an improvement of hippocampal-dependent working memory when repetitive information was presented in a single day. These findings suggest that adult-born cells in the dentate gyrus have different, and in some cases, opposite roles in distinct types of memory.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Stress and the brain: from adaptation to disease

Abstract: In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

The molecular neurobiology of depression

Abstract: Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.