The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre-and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.neural plasticity | dendritic spines | prenatal stress | psychoactive drugs | metaplasticity T he development of the cerebral cortex reflects more than a simple unfolding of a genetic blueprint; rather, it represents a complex dance of experiential and genetic factors that mold the emerging cerebrum. Pre-and postnatal environmental events, such as sensory stimuli, hormones, parent-child relationships, stress, and psychoactive drugs, modify cerebral development and, ultimately, adult behavior. Although all cerebral regions are influenced by early experience, the effects of experience are significantly different in specific cortical regions. The goal of this article is to review the ways in which one specific region, the prefrontal cortex (PFC), is sculpted by a wide range of pre-and postnatal factors. We begin with an overview of the nature and function of the PFC, followed by a review of experience-dependent modification of prefrontal organization and function. What Is the PFC?Kaas (1) proposed that a few basic areas of cerebral cortex are present in all mammals. These include primary and secondary visual and somatosensory areas (i.e., V1, V2, S1, S2), at least one auditory area and one taste area, a motor area, a transitional strip of cortex that relates the amygdala and hippocampus to other cortical areas (i.e., perirhinal cortex, entorhinal cortex), and a region referred to as the PFC. The definition of the sensory regions is relatively straightforward insofar as they receive unimodal input from the sensory receptor systems (e.g., eye, ear, tongue), and the outputs of the motor cortex are ultimately directed via polysynaptic pathways to effector organs. The outputs of all cortical regions are also components of feedback loops through which the cortex and subcortical regions of the brain mutually influence each other. Although there is no universally acceptable definition of the PFC, it can be regarded to be the region of the cortex that receives its principal thalamic inputs from the mediodorsal nucleus of the thalamus (e.g., 2). This cor...
Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a "click" reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.
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