Nervous system

About: Nervous system is a research topic. Over the lifetime, 16729 publications have been published within this topic receiving 847181 citations.

Brain waves and brain wiring: the role of endogenous and sensory-driven neural activity in development.

Abstract: Neural activity is critical for sculpting the intricate circuits of the nervous system from initially imprecise neuronal connections. Disrupting the formation of these precise circuits may underlie many common neurodevelopmental disorders, ranging from subtle learning disorders to pervasive developmental delay. The necessity for sensory-driven activity has been widely recognized as crucial for infant brain development. Recent experiments in neurobiology now point to a similar requirement for endogenous neural activity generated by the nervous system itself before sensory input is available. Here we use the formation of precise neural circuits in the visual system to illustrate the principles of activity-dependent development. Competition between the projections from lateral geniculate nucleus neurons that receive sensory input from the two eyes shapes eye-specific connections from an initially diffuse projection into ocular dominance columns. When the competition is altered during a critical period for these changes, by depriving one eye of vision, the normal ocular dominance column pattern is disrupted. Before ocular dominance column formation, the highly ordered projection from retina to lateral geniculate nucleus develops. These connections form before the retina can respond to light, but at a time when retinal ganglion cells spontaneously generate highly correlated bursts of action potentials. Blockade of this endogenous activity, or biasing the competition in favor of one eye, results in a severe disruption of the pattern of retinogeniculate connections. Similar spontaneous, correlated activity has been identified in many locations in the developing central nervous system and is likely to be used during the formation of precise connections in many other neural systems. Understanding the processes of activity-dependent development could revolutionize our ability to identify, prevent, and treat developmental disorders resulting from disruptions of neural activity that interfere with the formation of precise neural circuits.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

Abstract: Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Alterations in neural cell adhesion molecules during development of different regions of the nervous system.

Abstract: Several cell adhesion molecules involved in neuron-neuron and neuron-glia interactions have been identified in our laboratory and have been shown to undergo cell surface modulation. In the case of the neural cell adhesion molecule (N-CAM), it has been found that during development the molecule is converted from a microheterogeneous embryonic (E) form containing 30 gm of sialic acid/100 gm of polypeptide to several distinct adult (A) forms containing one third as much of this sugar. In vitro analyses indicate that this change is accompanied by a 4-fold increase in the rate of N-CAM homophilic binding. In the present study of the mouse and the chick, alterations of N-CAMs occurring as a result of E----A conversion, prevalence modulation, and changes in antigenic state during the development of different neural regions were analyzed by the use of highly specific polyclonal and monoclonal antibodies combined with anatomical dissection and several new quantitative assays. We made the following observations. The relative concentration of N-CAM changed during development, with the highest concentration (2.8 times the adult level) occurring around the perinatal period. Each brain region followed a similar pattern of change but according to a different time schedule. While conversion from the E to the A forms of N-CAM occurred mainly during the first 3 postnatal weeks in mice, the relative conversion rates were distinctly different in various neural tissues. The extreme examples are dorsal root ganglia, which already displayed the A forms at birth, and the diencephalon and tectal region, which still retained some E forms in the adult. A cephalocaudal maturation gradient of E----A conversion was observed in the spinal cord and dorsal root ganglia. Differences in the antigenic determinants of N-CAMs from different neural tissues were detected by two independent monoclonal antibodies. Finally, in some adult neural tissues, one of the three A forms was found to be dominant. These results establish that during development there are definite quantitative and qualitative differences among N-CAMs from various neural tissues. The data are consistent with the hypothesis that alterations in the relative amounts and forms of N-CAM play major roles in neural morphogenesis, possibly by altering the rates of adhesion among neurons and their processes.

Differential Expression of Glutamate Receptor Subunits in the Nervous System of Caenorhabditis elegans and Their Regulation by the Homeodomain Protein UNC-42

Abstract: In almost all nervous systems, rapid excitatory synaptic communication is mediated by a diversity of ionotropic glutamate receptors. In Caenorhabditis elegans, 10 putative ionotropic glutamate receptor subunits have been identified, a surprising number for an organism with only 302 neurons. Sequence analysis of the predicted proteins identified two NMDA and eight non-NMDA receptor subunits. Here we describe the complete distribution of these subunits in the nervous system of C. elegans. Receptor subunits were found almost exclusively in interneurons and motor neurons, but no expression was detected in muscle cells. Interestingly, some neurons expressed only a single subunit, suggesting that these may form functional homomeric channels. Conversely, interneurons of the locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six subunits, suggesting that these subunits interact to generate a diversity of heteromeric glutamate receptor channels that regulate various aspects of worm movement. We also show that expression of these subunits in this circuit is differentially regulated by the homeodomain protein UNC-42 and that UNC-42 is also required for axonal pathfinding of neurons in the circuit. In wild-type worms, the axons of AVA, AVD, and AVE lie in the ventral cord, whereas in unc-42 mutants, the axons are anteriorly, laterally, or dorsally displaced, and the mutant worms have sensory and locomotory defects.

Immunocytochemical localization of substance P in mammalian intestine.

Abstract: In mammalian intestine immunoreactive Substance P is localized not only in the plexuses of Auerbach and Meissner, as could be anticipated, but also in a number of basally situated, often basigranular, endocrine cells which have been identified tentatively as enterochromaffin. The presence of a neurohormone in cells of this type confirms their close association with the nervous system, noted by Masson (1924), and suggests that their postulated origin from the nervous system (Danisch, 1924) may well be correct.