Project 3:  Circuit Based Analysis of Fear Conditioning

Overall Goals

In order to develop the means by which neuroanatomical studies can be performed with the objectivity of direct biochemical or electrophysiological observations, it is important to recognize the need for rigorous quantification of neurochemically defined morphological details. It is therefore necessary to consider all levels of morphological resolution, from macroscopic features to subcellular characteristics, to provide a comprehensive understanding of neurochemical morphology not only in the context of functional circuits but also in relation to experimental paradigms. The quantitative morphology core is designed to provide all participants to the Center with 1) Extensive expertise in the most rigorous, modern neuroanatomical approaches, with an emphasis on quantitative anatomic techniques, such as stereology, mapping, and cell reconstruction; 2) Quantitative instruments designed to cross levels of resolution from macroscopic analysis to the analysis of confocal and electron microscopy materials; 3) Education in the use of these procedures, and assistance with experimental design and data analysis; 4) A high level of uniformity across the different projects in the Center in terms of quantitative study design and analysis, ensuring the necessary degree of consistency in view of the highly interactive nature of the Center; 5) A means to compare and validate quantitative data with other neuroscientists using similar methods, which will be particularly important in the context of stereologic analyses.

Literature Cited:

Bloom FE, Young WG, Nimchinsky EA, Hof PR, Morrison JH (1997) Neuronal vulnerability and informatics in human disease. In: Progress in neuroinformatics research Vol. 1, Neuroinformatics - An overview of the human brain project (Koslow SH, Huerta MF eds), pp 83-123. Mahwah: Lawrence Erlbaum.

Gazzaley AH, Siegel SJ, Kordower JH, Mufson EJ, Morrison JH (1996a) Circuit-specific alterations of N-methyl-D-aspartate subunit 1 in the dentate gyrus of aged monkeys. Proc Natl Acad Sci USA 93:3121-3125.

Gazzaley AH, Weiland NG, McEwen BS, Morrison J.H (1996b) Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. J Neurosci 16:6830-6838.

Gazzaley AH, Benson DL, Huntley GW, Morrison JH (1997a) Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection. J Neurosci 17:2006-2017.

Gazzaley AH, Thakker MM, Hof PR, Morrison JH (1997b) Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys. Neurobiol Aging 18:549-553.

Geinisman Y, Gundersen HJG, Van Der Zee E, West MJ (1996) Unbiased stereological estimation of the total number of synapses in a brain region. J Neurocytol 25:805-819.

Hof PR, Nimchinsky EA, Morrison JH (1995) Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices. J Comp Neurol 362:109-133.

Hof PR, Ungerleider LG, Webster MJ, Gattass R, Adams MM, Sailstad CA, Morrison JH (1996) Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways. J Comp Neurol 376:112-127.

Hof PR, Ungerleider LG, Adams MM, Webster MJ, Gattass R, Blumberg DM, Morrison JH (1997a) Callosally-projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein. Vis Neurosci 14:981-987.

Hof P.R., Nimchinsky E.A., Young W.G., Morrison J.H. (2000) Numbers of Meynert and layer IVB cells in area V1: a stereologic analysis in young and aged macaque monkeys. J. Comp. Neurol. 420, 113-126.

Morrison J.H., Hof P.R. (1998) Quantitative Neuroanatomy: A Picture is Worth a Thousand Words, but a Number is Worth a Thousand Pictures. Society for Neuroscience Short Course Syllabus, Society for Neuroscience, Washington, viii + 78 pp.

Morrison BM, Gordon JW, Ripps ME, Morrison JH (1996) Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: neurochemical correlates of selective vulnerability. J Comp Neurol 373:619-631.

Nimchinsky EA, Hof PR, Young WG, Morrison JH (1996a) Neurochemical, morphologic and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey. J Comp Neurol 374:136-160.

Nimchinsky E.A., Young W.G., Yeung G., Shah R.A., Gordon J.W., Bloom F.E., Morrison J.H., Hof P.R. (2000) Differential vulnerability of oculomotor, facial, and hypoglossal nuclei in G86R superoxide dismutase transgenic mice. J. Comp. Neurol. 416, 112-125.

Perl D.P., Good P.F., Bussière T., Morrison J.H., Erwin J.M., Hof P.R. (in press) Practical approaches to stereology in the setting of aging- and disease-related brain banks. J. Chem. Neuroanat.

Schmitz C., Hof P.R. (in press) Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach. J. Chem. Neuroanat.

Schmitz C., Hof P.R. (2000) Issue editors: Recent Advances in Neurostereology. J. Chem. Neuroanat. 20(1) 124 pp.

Schmitz, C., 1997. Towards more readily comprehensible procedures in disector stereology. J. Neurocytol. 26, 707-710.

Schmitz, C., 1998. Variation of fractionator estimates and its prediction. Anat. Embryol. 198, 371-397. Schmitz, C., 2000. Towards the use of state-of-the-art stereology in experimental gerontology. Exp. Gerontol. 35, 429-431.

Schmitz, C., Bültmann, E., Gube, M., Korr, H., 1999a. Neuron loss in the mouse hippocampus following prenatal injection of tritiated thymidine or saline. Int. J. Dev. Neurosci. 17, 185-190.

Schmitz, C., Rüb, U., Korr, H., Heinsen, H., 1999b. Nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease. II. Optimization of a stereological estimation procedure. Acta Neuropathol. 97, 623-628.

Thioulouse, J., Royet, J.P., Ploye, H., Houllier, F., 1993. Evaluation of the precision of systematic sampling: nugget effect and covariogram modelling. J. Microsc. 172, 249-256.

West MJ, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482-497.

West MJ, Østergaard K, Andreasen OA, Finsen B (1996a) Estimation of the number of somatostatin neurons in the striatum: an in situ hybridization study using the optical fractionator method. J Comp Neurol 370:11-22.

Young WG, Nimchinsky EA, Hof PR, Morrison JH, Bloom FE (1997) NeuroZoom software user guide and reference books, YBM Inc., San Diego, 1038 pages CD-ROM, http://neurozoom.scripps.edu/.