Object-centered spatial awareness--awareness of the location, relative to an object, of its parts--plays an important role in many aspects of perception, imagination, and action. One possible basis for this capability is the existence in the brain of neurons with sensory receptive fields or motor action fields that are defined relative to an object-centered frame. In experiments described here, neuronal activity was monitored in the supplementary eye field of macaque monkeys making eye movements to the right or left end of a horizontal bar. Neurons were found to fire differentially as a function of the end of the bar to which an eye movement was made. This is direct evidence for the existence of neurons sensitive to the object-centered direction of movements.

Estrogen induces a rapid increase in microvascular permeability in the rodent uterus, leading to stromal edema and a marked increase in uterine wet weight. This edema is believed to create an environment optimal for the growth and remodeling of the endometrium in preparation for implantation and pregnancy. Increased endometrial microvascular permeability also occurs in conjunction with implantation. Estrogen-induced uterine edema is immediately preceded by an increase in the expression of vascular endothelial growth factor (VEGF), a potent stimulator of microvascular permeability. The objective of this study was to determine to what degree immunoneutralization of VEGF would interfere with a) estradiol-induced uterine edema and b) pregnancy. In the first set of experiments, immature female rats were injected with either VEGF antiserum or normal rabbit serum (NRS) prior to 17beta-estradiol treatment. Rats treated with estradiol alone showed a 57% increase in uterine wet weight at 6 h compared with controls. Injection of 200 or 300 micro l of VEGF antiserum reduced the response to only 20% and 10% above controls, respectively. In the second set of experiments, young adult female mice were treated with 100 micro l of either VEGF antiserum or NRS at 1200 h on the fourth day after mating. NRS-treated mice had normal pregnancies. VEGF antiserum, however, completely blocked pregnancy. When VEGF antiserum-treated females were examined on Day 5 for the presence of implantation sites, none were found. These results show that a) VEGF is the major mediator of estrogen-induced increase in uterine vascular permeability and b) VEGF-induced edema is absolutely essential for implantation to take place.

Development of the ovarian follicle and corpus luteum involves proliferation and differentiation of several cell types: granulosa cells, thecal cells, and various stromal cells, particularly the endothelial cells that compose the rich thecal and luteal vascular networks. Basic fibroblast growth factor (bFGF) is a potent mitogen for cells of mesodermal and neuroectodermal origin, including endothelial cells. With the use of reverse transcription-polymerase chain reaction (PCR), we have examined the expression of bFGF in the rat ovary. RNA was extracted from fetal bovine aortic endothelial cells, hypothalami of adult rats, and either whole ovaries or isolated granulosa cells from PMSG-primed immature rats. The RNA was reverse transcribed and then amplified by PCR using two oligonucleotide primers specific for both bovine and rat bFGF. A sample of the PCR solution was size fractionated by electrophoresis in an 8% polyacrylamide gel, which was then stained with ethidium bromide and examined under ultraviolet light. When reverse transcription-PCR was performed on RNA from bovine endothelial cells, rat hypothalamus, or whole rat ovary, a single major DNA band corresponding in length to the distance between the 5'-ends of the two bFGF-specific primers (354 base pairs) was obtained. The identity of this material with the bovine and rat bFGF sequences was confirmed by restriction enzyme analysis. When RNA from isolated granulosa cells was examined, however, no bFGF mRNA was detected. These results confirm that the bFGF gene is expressed in the ovary during follicular development. Furthermore, they demonstrate that ovarian bFGF expression is cell specific, since granulosa cells do not contain detectable bFGF mRNA.

The expression of mRNAs coding for the a subunit of rat brain and rat heart sodium channels has been studied in adult and neonatal rat cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). Rat brain sodium channel subtype I, H, HA, and HI sequences were simultaneously amplified in the same PCR using a single oligonucleotide primer pair matched to all four subtype sequences. Identification of each subtype-specific product was inferred from the appearance of unique fragments when the product was digested with specific restriction enzymes. By using this RT-PCR method, products arising from mRNAs for all four brain sodium channel subtypes were identified in RNA extracted from adult rat cerebral cortex. The predominant component was type HA with lesser levels of types I,1, and m.In contrast, the type II and HA sequences were the predominant RT-PCR products in neonatal rat cortex, with slightly lower levels of type M and undetectable levels of type I. Thus, from neonate to adult, type H mRNA levels decrease relative to type HA levels. Using a similar approach, we detected mRfVA coding for the rat heart sodium channel in neonatal and adult rat cerebral cortex and in adult rat heart. These results reveal that mRNAs coding for the heart sodium channel and all four previously sequenced rat brain sodium channel subtypes are expressed in cerebral cortex and that type H and HA channels may be differentially regulated during development.Voltage-dependent sodium channels are responsible for action-potential generation and propagation in many excitable cells, including cardiac and skeletal muscle and neurons (1). Although virtually all sodium channels appear to have very similar functional properties, minor differences are observed among sodium channels from various cells in the same organism and, in some cases, within the same cell. One notable functional property that differs considerably among tissues is the sensitivity to the guanidinium toxins tetrodotoxin (TTX) and saxitoxin (STX). Sodium channels in central nervous system neurons and skeletal muscle are normally blocked by nanomolar concentrations of TTX and STX, whereas channels in cardiac cells and denervated skeletal muscle are relatively TTX/STX-resistant, requiring 0.1-10 AM toxin for block (2). Some cell types, including developing skeletal muscle myocytes (3-5), certain peripheral (dorsal root ganglion) neurons (6, 7), and some brain glial cells (astrocytes) (8-10), express both high-TTX-affinity and low-'ITX-affinity sodium channels. The physiological consequences of these differences are not known.Biochemical and molecular biological studies have provided considerable information about the molecular structures of voltage-gated ion channels. All sodium channels thus far characterized contain a large (260 kDa) a subunit and, in some cases, one or two smaller (30-40 kDa) p subunits (11-13). Hydropathy analysis of the primary amino acid sequence suggests that the a subunit consists of four homologous domains each containing six ...

We thank John Maunsell for assistance and the use of the recording laboratory, and Larry Ota and Kathy Lazaroff for excellent technical assistance. We are also grateful to Emil Rainero for developing the computer software for stimulus generation and the control of experiments, Dorothy Flood for help with histological analysis, and William Merigan for comments on the manuscript.