1985 |
Lin, Rick C.s. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Structure and Function of Visual Cortex
The main goal of the proposed research is to study the functional organization of visual cortex in the rat. First, we plan to identify the morphology of specific neuron populations which project to known extrinsic targets. We will continue to use a new modified technique (Fran et al. '80) of adding lysolecithin to horesradish peroxidase (HRP) and then ionto- phoretically injecting this mixture via a micropipette (tip sixe 10 Mum) with either ster- eotaxid and/or electrophysiologcal identification of appropriate brain regions. The detailed morphological classes of homogenously backfilled neurons of a particular pathway will be analyzed. In related experiments, collateral axonal projections will be studied by injecting suspected targets with two different fluorescent dyes. The potential results from these studies will set the stage for our functional analysis of neurons via intracellular recording and morphological identification. Second, we will continue the quantitative analysis of single neurons in terms of their receptive field properties by extracellular recording and their afferent and efferent connections determined by electrically stimulating known sources of inputs to the visual cortex such as the thalamus and contralateral cortex. Then the neuron will be peneatrated by the microlectrode, rechecked to ensure the identity of the neuron and injected with HRP. The HRP-filling reveals a detailed morphology including the dendritic and axonal branching patterns. An attempt will be made to correlate the dendritic and/or axonal arborization patterns to response properties such as orientation and direction selectivities, receptive field size, affarent and efferent connections and conduction velocity. In conclusion, we expect that these approaches will provide valuable insights and establish relationships between the neuronal morphology and physiological properties as well as known extrinsic projections.
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0.906 |
2000 — 2003 |
Lin, Rick C.s. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Physiology and Anatomy of Zona Incerta @ University of Mississippi Medical Center |
0.936 |
2008 — 2011 |
Lin, Rick C.s. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Serotonin, Corpus Callosum, and Autism @ University of Mississippi Medical Center
[unreadable] DESCRIPTION (provided by applicant): Autism spectrum disorder or Autism (ASD) is among one of the most devastating neurodevelopmental disorders in the United States. The most current epidemiological data have suggested that this disorder may affect as many as 1 in 150 children. Unfortunately, the scientific community is at a loss to explain the increased prevalence of this disorder among the American population in recent years. Based on limited neuropathological and fMRI studies, investigators have been able to determine that the most consistent anatomical abnormality in ASD relates to a reduction in the size of the corpus callosum (a major fiber bundle in the brain which connects the two cerebral hemispheres). In the absence of a suitable animal model for ASD, we have learned that serotonin (5HT) plays a critical role during early brain development, and that 5HT synthesis is altered in autistic individuals at early ages. Importantly, our recently published data and other lines of evidence have revealed that brief perinatal exposure of rat pups to the selective serotonin reuptake inhibitor (SSRI), citalopram, can alter uptake of fluorescent tracer from one cerebral hemisphere to another and lead to malformation of myelin sheaths around callosal axons. Hence, our central hypothesis is that abnormal regulation of 5HT during early brain development compromises oligodendrocyte function and interferes with the establishment of normal interhemispheric connections. To address our hypothesis, multi-disciplinary approaches which include anatomy, immunohistochemistry, physiology, pharmacology, behavior, as well as cell culture will be simultaneously conducted from a group of world leading scientists at three different institutions. These studies are designed to define the possible role of serotonin dysregulation in the genesis of autism and related pervasive developmental disorders. We believe that our proposed exploratory studies hold great promise in identifying a future animal model for ASD, and hold the key to linking serotonin dysfunction during early brain development to increased rates of maternal SSRI usage during pregnancy and nursing. Our findings should 1) shape public policy regarding the identification and rehabilitation of individuals with ASD, and 2) help to establish antidepressant treatment guidelines for new and expectant mothers. Neurodevelopmental disorders have a tremendous impact on our society. At present, autism spectrum disorder (ASD) is among one of the most devastating diseases affecting children in terms of prevalence, morbidity, disruption to family life, and cost to the public. According to the most recent epidemiological data, ~ 1 child in 150 suffers from ASD. However, the etiology of this disorder is largely unknown. Interestingly, ASD is characterized by a reduction in the size of the corpus callosum; a sign of underconnectivity between the two cortical hemispheres. Based on our preliminary data and other lines of evidence, we propose that dysfunction of the raphe serotonin (5HT) system during early development may be one of the most important factors contributing to ASD. The most challenging and clinical relevant aspects of this proposal is our attempt to link recent drastic increase of ASD to the increased number of mothers taking antidepressant drugs, namely selective serotonin reuptake inhibitors (SSRIs), during pregnancy and nursing. Hence, our central hypothesis is that abnormal regulation of 5HT during early brain development interferes with myelin formation and the establishment of normal inter-hemispheric connections. The proposed experiments are designed to address this hypothesis by studying anatomical, neurochemical, physiological, and behavioral effects of perinatal citalopram (the most selective SSRI) exposure on rats aged to postnatal days 22 and >90. [unreadable] [unreadable]
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0.936 |