Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calciuminduced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of ,uCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolyticafly activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of ,uCANP in Alzheimer disease, the ratio of the 76-kDa

In order to describe the circuitry of a single retinal X-cell axon in the lateral geniculate nucleus, we physiologically characterized such an axon in the optic tract and injected it intra-axonally with horseradish peroxidase. Subsequently, we recovered the axon and employed electron microscopic techniques to examine the distribution of synapses from 18% of its labeled terminals by reconstructing the unlabeled postsynaptic neurons through a series of 1,200 consecutive thin sections. We found remarkable selectivity for the axon's output, since only four of the 43 available neurons in a limited portion of the terminal arbor receive synapses from labeled terminals. Moreover, the distribution of these synapses on the four neurons, which we term cells 1 through 4, varies with respect to synapses from other classes of terminals that contact the same cells, including synapses from unlabeled retinal terminals. For cells 1 and 3, the labeled terminals provide 49% and 33%, respectively, of their retinal synapses, and these are located on both dendritic shafts and appendages. Synapses from the injected axon to these cells are thus integrated with those from other retinal axons. For cell 2, the labeled terminals provide 100% of its retinal synapses, but these synapses converge on clusters of dendritic appendages where they are integrated with convergent inhibitory inputs. Finally, for cell 4, the labeled terminals provide less than 2% of its retinal inputs, and these are distally located; we suggest that these synapses are remnants of physiologically inappropriate miswiring that occurs during development. The findings from this study support a concept of selectivity in neuronal circuitry in the mammalian central nervous system and also reveal some of the diverse integrative properties of neurons in the lateral geniculate nucleus.

Although receptive fields of relay cells in the lateral geniculate nucleus of the cat nearly match those of their retinal afferents, only 10-20% of the synapses on these cells derive from the retina and are excitatory. Many more (30-40%) are inhibitory and largely control the gating of retinogeniculate transmission. These inhibitory synapses derive chiefly from two cell types: intrinsic local circuit neurones and cells in the adjacent perigeniculate nucleus. It has been difficult to study the functional organization of these inhibitory pathways; most efforts have relied on indirect approaches. Here we describe the use of direct techniques to study a local circuit neurone by iontophoresing horseradish peroxidase (HRP) into it, which completely labels the soma and processes of cells for subsequent light- and electron microscopic analysis. Although the response properties of the labelled cell are virtually indistinguishable from those of many relay cells, its morphology is typical of 'class 3' neurones (see Fig. 1 legend), which are widely believed to be interneurones (but see ref. 12). Here, we refer to the cell as a 'local circuit neurone', which allows for the possibility of a projection axon, rather than as an 'interneurone', a term that commonly excludes a projection axon. We find that the labelled cell has a myelinated axon, but that the axon loses its myelin within 50 microns of the soma and has not yet been traced further. The dendrites of the labelled cell possess presynaptic terminals that act as intrinsic sources of inhibition on geniculate relay cells. We also characterize other morphological aspects of this inhibitory circuitry.