A Family of Activity-Dependent Neuronal Cell-Surface Chondroitin Sulfate Proteoglycans in Cat Visual Cortex

Abstract

Monoclonal antibody Cat-301 recognizes a chondroitin sulfate proteoglycan (CSPG) expressed on the extracellular surface of cell bodies and proximal dendrites of specific subsets of neurons in many areas of the mammalian CNS, including the cat visual cortex. The Cat-301 CSPG is first detected at the close of the critical period in development, a period during which the pattern of neuronal activity determines the mature synaptic circuitry and neuronal phenotype. In the cat visual cortex, dark-rearing from birth prolongs the duration of the critical period and attenuates the expression of the Cat-301 antigen, implicating the Cat-301 CSPG in the cellular mechanisms that terminate the period of synaptic plasticity. Because the Cat-301 antigen is expressed on only a limited subset of neurons, we have further examined the molecular heterogeneity among neuronal cell-surface CSPGs and have asked (1) whether other neuronal subsets carry distinct CSPGs and (2) whether the activity-dependent expression of the Cat-301 CSPG is a property generalizable to related cell-surface CSPGs. Here, we report two new monoclonal antibodies, Cat-315 and Cat-316, which together with Cat-301 define a family of at least seven related yet distinct CSPGs. These three antibodies define nonidentical subsets of neurons in the cat visual cortex. The expression of normal levels of these CSPGs is reduced by darkrearing. Together, these data show that the family of cellsurface CSPGs is molecularly diverse, that different sets of neurons express distinct complements of cell-surface antigens, and that the regulation of CSPG expression by activity may be a general feature of neuronal cell-surface CSPGs.

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

“…For example, increased PV and WFA labeling during the closure of critical periods in sensory cortices is likely driven by increased excitatory input (McRae and Porter, 2012). In addition, both aggrecan expression (McRae et al, 2010) and glycosylation state (Lander et al, 1997) are activity-dependent. Because DLPFC layer 3 PCs appear to receive fewer excitatory synaptic inputs (Glantz and Lewis, 2000) resulting in a lower expression of gene products critical for energy production (Arion et al, 2015), their lower activity would result in less excitatory drive to neighboring layer 3 PV cells (which receive a large proportion of their excitatory inputs from layer 3 PCs (Melchitzky et al, 1998).…”

Extracellular matrix of the central nervous system: from neglect to challenge

“…Since ex vivo isolates of the highly glycosylated molecules were frequently used for immunization, several monoclonal antibodies have recognized carbohydrate epitopes, which could be found in glycans of several glycoproteins and/or were sometimes only present in subfractions of a particular ECM component (Lander et al 1997;Matthews et al 2002;Yamagata et al 1993;Zako et al 2002). Another cause for antibody cross-reactivity has also been the high protein sequence conservation, as in the G1 and G3 domains of the lecticans, and the consequent epitope sharing Perides et al 1993;Yamada et al 1997b).…”

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

“…Outside the cerebellar cortex, this antibody recognizes multiple types of neurons, and its antigen is subject to developmental and activity-dependent regulation (Lander et al 1997). Molecularly, it has been identiWed as a distinctly glycosylated form of the extracellular matrix protein, aggrecan, which forms part of perineuronal nets (Lander et al 1998;Matthews et al 2002).…”