Synaptic plasticity in the subiculum

The subiculum is the principal target of CA1 pyramidal cells. It functions as a mediator of hippocampal–cortical interaction and has been proposed to play an important role in the encoding and retrieval of long-term memory. The cellular mechanisms of memory formation are thought to include long-term potentiation (LTP) and depression (LTD) of synaptic strength. This review summarizes the contemporary knowledge of LTP and LTD at CA1–subiculum synapses. The observation that the underlying mechanisms of LTP and LTD at CA1–subiculum synapses correlate with the discharge properties of subicular pyramidal cell reveals a novel and intriguing mechanism of cell-specific consolidation of hippocampal output.     

Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome

Down syndrome (DS) is the leading cause of genetically-defined intellectual disability and congenital birth defects. Despite being one of the first genetic diseases identified, only recently, thanks to the phenotypic analysis of DS mouse genetic models, we have begun to understand how trisomy may impact cognitive function. Cognitive disabilities in DS appear to result mainly from two pathological processes: neurogenesis impairment and Alzheimer-like degeneration. In DS brain, suboptimal network architecture and altered synaptic communication arising from neurodevelopmental impairment are key determinants of cognitive defects. Hypocellularity and hypoplasia start at early developmental stages and likely depend upon impaired proliferation of neuronal precursors, resulting in reduction of numbers of neurons and synaptic contacts. The impairment of neuronal precursor proliferation extends to adult neurogenesis and may affect learning and memory. Neurodegenerative mechanisms also contribute to DS cognitive impairment. Early onset Alzheimer disease occurs with extremely high incidence in DS patients and is causally-related to overexpression of β-amyloid precursor protein (βAPP), which is one of the triplicated genes in DS. In this review, we will survey the available findings on neurodevelopmental and neurodegenerative changes occurring in DS throughout life. Moreover, we will discuss the potential mechanisms by which defects in neurogenesis and neurodegenerative processes lead to altered formation of neural circuits and impair cognitive function, in connection with findings on pharmacological treatments of potential benefit for DS.     

Emerging themes in GABAergic synapse development

Glutamatergic synapse development has been rigorously investigated for the past two decades at both the molecular and cell biological level yet a comparable intensity of investigation into the cellular and molecular mechanisms of GABAergic synapse development has been lacking until relatively recently. This review will provide a detailed overview of the current understanding of GABAergic synapse development with a particular emphasis on assembly of synaptic components, molecular mechanisms of synaptic development, and a subset of human disorders which manifest when GABAergic synapse development is disrupted. An unexpected and emerging theme from these studies is that glutamatergic and GABAergic synapse development share a number of overlapping molecular and cell biological mechanisms that will be emphasized in this review.     

Brain excitability and connectivity of neuronal assemblies in Alzheimer's disease: From animal models to human findings

The human brain contains about 100 billion neurons forming an intricate network of innumerable connections, which continuously adapt and rewire themselves following inputs from external and internal environments as well as the physiological synaptic, dendritic and axonal sculpture during brain maturation and throughout the life span.     

The acidic tumour microenvironment: Manipulating the immune response to elicit escape

The success of cancer treatment relies on the composition of the tumour microenvironment which is comprised of tumour cells, blood vessels, stromal cells, immune cells, and extracellular matrix components. Barriers to effective cancer treatment need to be overcome, and the acidic microenvironment of the tumour provides a key target for treatment. This review intends to provide an overview of the effects that low extracellular pH has on components of the tumour microenvironment and how they contribute to immune escape. Further, potential therapeutic targets will be discussed.