Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hippocampal CA1 pyramidal neurons: Ca(2+)-dependent activation by blocking A1 adenosine receptors.

When performed at increased external [Ca2+]/[Mg2+] ratio (2.5 mM/0.5 mM), temporary block of A1 adenosine receptors in hippocampus [by 8-cyclopentyltheophylline (CPT)] leads to a dramatic and irreversible change in the excitatory postsynaptic current (EPSC) evoked by Schaffer collateral/commissural (SCC) stimulation and recorded by in situ patch clamp in CA1 pyramidal neurons. The duration of the EPSC becomes stimulus dependent, increasing with increase in stimulus strength. The later occurring component of the EPSC is carried through N-methyl-D-aspartate (NMDA) receptor-operated channels but disappears under either the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These findings indicate that the late component of the SCC-evoked EPSC is polysynaptic: predominantly non-NMDA receptor-mediated SCC inputs excite CA1 neurons that recurrently excite each other by predominantly NDMA receptor-mediated synapses. These recurrent connections are normally silent but become active after CPT treatment, leading to enhancement of the late component of the EPSC. The activity of these connections is maintained for at least 2 hr after CPT removal. When all functional NMDA receptors are blocked by dizocilpine maleate (MK-801), subsequent application of CPT leads to a partial reappearance of NMDA receptor-mediated EPSCs evoked by SCC stimulation, indicating that latent NMDA receptors are recruited. Altogether, these findings indicate the existence of a powerful system of NMDA receptor-mediated synaptic contacts in SCC input to hippocampal CA1 pyramidal neurons and probably also in reciprocal connections between these neurons, which in the usual preparation are kept latent by activity of A1 receptors.

Intracellular polyamines mediate inward rectification of Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are Ca(2+)-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca(2+)-permeable inwardly rectifying AMPA receptor currents. Inward rectification in these neurons was lost with intracellular dialysis and was not present in excised outside-out patches but was maintained in perforated-patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturally occurring polyamines spermine and spermidine in the recording pipette prevented loss of rectification in both whole-cell and excised-patch recordings; Mg2+ and putrescine were without effect. Inward rectification of Ca(2+)-permeable AMPA receptors may reflect voltage-dependent channel block by intracellular polyamines.

Molecular cloning and functional characterization of the Xenopus Ca(2+)-binding protein frequenin.

Frequenin was originally identified in Drosophila melanogaster as a Ca(2+)-binding protein facilitating transmitter release at the neuromuscular junction. We have cloned the Xenopus frequenin (Xfreq) by PCR using degenerate primers combined with low-stringency hybridization. The deduced protein has 70% identity with Drosophila frequenin and about 38-58% identity with other Ca(2+)-binding proteins. The most prominent features are the four EF-hands, Ca(2+)-binding motifs. Xfreq mRNA is abundant in the brain and virtually nondetectable from adult muscle. Western blot analysis indicated that Xfreq is highly concentrated in the adult brain and is absent from nonneural tissues such as heart and kidney. During development, the expression of the protein correlated well with the maturation of neuromuscular synapses. To determine the function of Xfreq at the developing neuromuscular junction, the recombinant protein was introduced into Xenopus embryonic spinal neurons by early blastomere injection. Synapses made by spinal neurons containing exogenous Xfreq exhibited a much higher synaptic efficacy. These results provide direct evidence that frequenin enhances transmitter release at the vertebrate neuromuscular synapse and suggest its potential role in synaptic development and plasticity.

Calmodulin is a selective mediator of Ca(2+)-induced Ca2+ release via the ryanodine receptor-like Ca2+ channel triggered by cyclic ADP-ribose.

The ryanodine receptor-like Ca2+ channel (RyRLC) is responsible for Ca2+ wave propagation and Ca2+ oscillations in certain nonmuscle cells by a Ca(2+)-induced Ca2+ release (CICR) mechanism. Cyclic ADP-ribose (cADPR), an enzymatic product derived from NAD+, is the only known endogenous metabolite that acts as an agonist on the RyRLC. However, the mode of action of cADPR is not clear. We have identified calmodulin as a functional mediator of cADPR-triggered CICR through the RyRLC in sea urchin eggs. cADPR-induced Ca2+ release consisted of two phases, an initial rapid release phase and a subsequent slower release. The second phase was selectively potentiated by calmodulin which, in turn, was activated by Ca2+ released during the initial phase. Caffeine enhanced the action of calmodulin. Calmodulin did not play a role in inositol 1,4,5-trisphosphate-induced Ca2+ release. These findings offer insights into the multiple pathways that regulate intracellular Ca2+ signaling.

Florence, Italy, ca. 1690 (Image 2 of 9) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova pvlcherrimaae civitatis Florentiaae topographia accuratissime delineata. It was published by Gio. Iacomo de Rossi ca. 1690. Scale ca. 1:24,000. This layer is image 2 of 9 total images of the nine sheet source map, representing the central east portion of the map. Map in Latin.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 32N projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, ground cover, and more. Relief and selected features shown pictorially.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Switzerland, ca. 1715 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova Helvetiae tabula geographica : illustrissimis et potentissimis cantonibus et rebuspublicis reformatae religionis Tigurinae, Bernensi, Glaronensi, Basiliensi, Scaphusianae, Abbatis Cellanae, dominis suis clementissimis humillime [de]dicata a Ioh. Iacobo Scheuchzero Tigurino med. d. math. prof. It was published by ex officin â Petri Schenkii, in platea vulgo de Warmoesstraat sub signo N. Visschers Athlas ca. 1715. Covers Switzerland. Scale [ca. 1:378,000]. This layer is image 2 of 4 total images of the four sheet source map, representing the southwest portion of the map. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial and administrative boundaries, roads, and more. Relief shown pictorially. Includes also illustrations. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Westerschelde, Netherlands and Belgium, ca. 1799 (Image 2 of 3) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Reconnoissance du cours du Hont ou Wester Schelde (Escaut occidental) depuis Anwerpen (Anvers) jusqu'à l'embouchure, faite par ordre du Ministre de la marine et des colonies, en thermidor et fructidor, an VII, vendémiaire et brumaire, an VIII, par Beautemps-Beaupré; assisté des Cens. Daussy et Portier, et de Jh. Raoul. It was published ca. 1799. Scale [ca. 1:41,300]. Covers Westerschelde, Netherlands and Belgium, from Middelburg to Antwerp. This layer is image 2 of 3 total images of the three sheet source map, representing the center portion of the map. Map in French.The image inside the map neatline is georeferenced to the surface of the earth and fit to the RD_New (Rijksdriehoekstelsel), GCS Amersfoort coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows coastal features such as rocks, channels, points, ports, coves, islands, flats, canals, and more. Includes also selected land features such as roads, towns, fortification, drainage, land cover, selected buildings, and more. Relief shown pictorially and with hachures. Depths shown by contours and soundings. Includes "Nota" and text with insigne of the Dépôt général de la marine.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Bergen op Zoom, Netherlands, ca. 1747 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la forte ville de Berguen op den Zoom avec ses lignes, attaques, et le Fort Steenberguen, desinè par Albert d'Herbort, Ingenieur. It was published by publié par Matthieu Seutter, Geogr. Imperial ca. 1747. Scale [ca. 1:20,000]. Covers Bergen op Zoom, Netherlands. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the RD_New (Rijksdriehoekstelsel), GCS Amersfoort coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, villages and other human settlements, fortifications, lines of fire, ground cover, and more. Relief shown pictorially and by hachures. Includes index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Bergen op Zoom, Netherlands, ca. 1747 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la forte ville de Berguen op den Zoom avec ses lignes, attaques, et le Fort Steenberguen, desinè par Albert d'Herbort, Ingenieur. It was published by publié par Matthieu Seutter, Geogr. Imperial ca. 1747. Scale [ca. 1:20,000]. Covers Bergen op Zoom, Netherlands. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the RD_New (Rijksdriehoekstelsel), GCS Amersfoort coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, villages and other human settlements, fortifications, lines of fire, ground cover, and more. Relief shown pictorially and by hachures. Includes index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

East Asia, ca. 1749 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Tartariae Sinensis mappa geographica : ex Tabulis specialibus RRPP Iesuitarum nec non Relationibus R.P. Gerbillon, per Dom d'Anville, ... primum A° 1732 nunc se ; nunc secundum LL. projectionis stereographicae in usum translationis Germanicae Historiae Sinens. Haldianae descripta per Tobiam Mayer. It was published by Curis Homannianorum Heredum ca. 1749. Scale [ca 1:5,250,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map. Covers a portion of East Asia including North Korea, South Korea, Mongolia, and portions of China, Russia, and Japan. Map in Latin and French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, the Great Wall of China, and more. Relief shown pictorially. Includes notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

East Asia, ca. 1749 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Tartariae Sinensis mappa geographica : ex Tabulis specialibus RRPP Iesuitarum nec non Relationibus R.P. Gerbillon, per Dom d'Anville, ... primum A° 1732 nunc se ; nunc secundum LL. projectionis stereographicae in usum translationis Germanicae Historiae Sinens. Haldianae descripta per Tobiam Mayer. It was published by Curis Homannianorum Heredum ca. 1749. Scale [ca 1:5,250,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the eastern portion of the map. Covers a portion of East Asia including North Korea, South Korea, Mongolia, and portions of China, Russia, and Japan. Map in Latin and French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, the Great Wall of China, and more. Relief shown pictorially. Includes notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

La Gironde Rivière Area, Bordeaux, France, ca. 1910 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de Bordeaux. It was published ca. 1910. Scale 1:10,000. Covers La Gironde Rivière area, Bordeaux, France. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM 30N' projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, built-up areas and selected buildings and industries, docks and wharves, and more. Includes manuscript additions. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

La Gironde Rivière Area, Bordeaux, France, ca. 1910 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de Bordeaux. It was published ca. 1910. Scale 1:10,000. Covers La Gironde Rivière area, Bordeaux, France. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM 30N' projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, built-up areas and selected buildings and industries, docks and wharves, and more. Includes manuscript additions. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Africa, ca. 1865 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Stanford's library map of Africa, constructed by A. Keith Johnston. It was published by Edward Stanford ca. 1865. Scale 1:5,977,382. This layer is image 2 of 4 total images of the four sheet source map, representing the southeast portion of the map. Covers also a small portion of Europe and the Middle East. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Africa Sinusoidal projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, roads, railroads, selected buildings and historical points of interest, territorial boundaries, shoreline features, and more. Relief shown by hachures. Includes notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.