18 research outputs found
NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex
SummaryNeurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPARs) contributed background depolarization to sustain network firing. In contrast, many Response cells were sensitive to AMPAR blockade and increased firing after systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer’s disease profoundly impair cognition
Molecular modulation of prefrontal cortex: Rational development of treatments for psychiatric disorders.
Human Stem Cells and Surrogate Tissues for Basic and Translational Study of Mental Disorders
Starting a Medical Technology Venture as a Young Academic Innovator or Student Entrepreneur
Following the footprints of Bill Gates, Steve Jobs and Mark Zuckerberg, there has been a misconception that students are better off quitting their studies to bring to life their ideas, create jobs and monetize their inventions. Having historically transitioned from manpower to mind power, we live in one of the most rapidly changing times in human history. As a result, academic institutions that are supposed to be pioneers and educators of the next generations have started to realize that they need to adapt to a new system, and change their policies to be more flexible towards patent ownership and commercialization. There is an infrastructure being developed towards students starting their own businesses while continuing with their studies. This paper aims to provide an overview of the existing landscape, the exciting rewards as well as risks awaiting a student entrepreneur, the challenges of the present ecosystem, and questions to consider prior to embarking on such a journey. Various entities influencing the start-up environment are considered, specifically for the medical technology sector. These parties include but are not limited to: scientists, clinicians, investors, academic institutions and governments. A special focus will be set on the seemingly unbridgeable gap between founding a company and a scientific career. Keywords: Entrepreneurship, Bioentrepreneur, Student entrepreneurship, Medical device
Neuronal basis of agerelated working memory decline. Nature 476
Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction Our society is rapidly ageing, with the number of seniors in the United States expected to double by 2050 (United States census, http://www.census.gov/population/www/pop-profile/elderpop.html). At the same time, the information age requires increasing organizational skills to deal with even basic needs such as medical care and paying bills. However, executive and working memory functions decline early in the normal ageing process In primates, spatial working memory depends on the highly evolved dorsolateral PFC 6 Monkeys (Macaca mulatta, n 5 6) were trained to perform a spatial working memory task in which they have to remember a spatial location over a brief delay period; the spatial location changes randomly on each tria
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Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
BackgroundPsychiatric disorders such as schizophrenia are worsened by stress, and working memory deficits are often a central feature of illness. Working memory is mediated by the persistent firing of prefrontal cortical (PFC) pyramidal neurons. Stress impairs working memory via high levels of dopamine D1 receptor (D1R) activation of cyclic adenosine monophosphate signaling, which reduces PFC neuronal firing. The current study examined whether D1R-cyclic adenosine monophosphate signaling reduces neuronal firing and impairs working memory by increasing the open state of hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels, which are concentrated on dendritic spines where PFC pyramidal neurons interconnect.MethodsA variety of methods were employed to test this hypothesis: dual immunoelectron microscopy localized D1R and HCN channels, in vitro recordings tested for D1R actions on HCN channel current, while recordings in monkeys performing a working memory task tested for D1R-HCN channel interactions in vivo. Finally, cognitive assessments following intra-PFC infusions of drugs examined D1R-HCN channel interactions on working memory performance.ResultsImmunoelectron microscopy confirmed D1R colocalization with HCN channels near excitatory-like synapses on dendritic spines in primate PFC. Mouse PFC slice recordings demonstrated that D1R stimulation increased HCN channel current, while local HCN channel blockade in primate PFC protected task-related firing from D1R-mediated suppression. D1R stimulation in rat or monkey PFC impaired working memory performance, while HCN channel blockade in PFC prevented this impairment in rats exposed to either stress or D1R stimulation.ConclusionsThese findings suggest that D1R stimulation or stress weakens PFC function via opening of HCN channels at network synapses