Genetics. In the article "Conservation of sequence and structure flanking the mouse and human ␤-globin loci: The ␤-globin genes are embedded within an array of odorant receptor genes" by Michael Bulger, J. Hikke von Doorninck, Noriko Saitoh, Agnes Telling, Catherine Farrell, M. A. Bender, Gary Felsenfeld, Richard Axel, and Mark Groudine, which appeared in number 9, April 27, 1999 of Proc. Natl. Acad. Sci. USA (96,(5129)(5130)(5131)(5132)(5133)(5134), the authors request that the following change be noted. Due to a printer's error, the author's name, J. Hikke von Doorninck, is misspelled and should be J. Hikke van Doorninck.Neurobiology. In the article "The effect of dynamic synapses on spatiotemporal receptive fields in visual cortex" by Ö mer B. Artun, Harel Z. Shouval, and Leon N. Cooper, which appeared in number 20, September 29, 1998, of Proc. Natl. Acad. Sci. USA (95, 11999 -12003), the legend for Neurobiology. In the article "Fluctuations and stimulusinduced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex" by David Kleinfeld, Partha P. Mitra, Fritjof Helmchen, and Winfried Denk, which appeared in number 26, December 22, 1998, of Proc. Natl. Acad. Sci. USA, the authors request that the following correction be noted. Two-photon laser scanning microscopy was used to measure the flow of red blood cells in capillaries in the living brain. In this manuscript, we also reported the length-constant for attenuation of the signal (i.e., two-photon excited fluorescence) as a function of penetration depth into the cortex. As a result of an error in our analysis, the length-constants for each data set were overestimated. The correct value for the data of Fig. 1 is 100 m (instead of 140 m), and the range of values over all data sets is from 100 m to 170 m (instead of 120 m to 220 m). We apologize for any inconvenience caused by our error. None of the other results or conclusions in the original manuscript are affected. Communicated by Harry Suhl, University of California at San Diego, La Jolla CA, October 20, 1998 (received for review August 13, 1998 ABSTRACT Cortical blood f low at the level of individual capillaries and the coupling of neuronal activity to f low in capillaries are fundamental aspects of homeostasis in the normal and the diseased brain. To probe the dynamics of blood f low at this level, we used two-photon laser scanning microscopy to image the motion of red blood cells (

The dendrites of mammalian pyramidal neurons contain a rich collection of active conductances that can support Na+ and Ca2+ action potentials (for a review see ref. 1). The presence, site of initiation, and direction of propagation of Na+ and Ca2+ action potentials are, however, controversial, and seem to be sensitive to resting membrane potential, ionic composition, and degree of channel inactivation, and depend on the intensity and pattern of synaptic stimulation. This makes it difficult to extrapolate from in vitro experiments to the situation in the intact brain. Here we show that two-photon excitation laser scanning microscopy can penetrate the highly scattering tissue of the intact brain. We used this property to measure sensory stimulus-induced dendritic [Ca2+] dynamics of layer 2/3 pyramidal neurons of the rat primary vibrissa (Sm1) cortex in vivo. Simultaneous recordings of intracellular voltage and dendritic [Ca2+] dynamics during whisker stimulation or current injection showed increases in [Ca2+] only in coincidence with Na+ action potentials. The amplitude of these [Ca2+] transients at a given location was approximately proportional to the number of Na+ action potentials in a short burst. The amplitude for a given number of action potentials was greatest in the proximal apical dendrite and declined steeply with increasing distance from the soma, with little Ca2+ accumulation in the most distal branches, in layer 1. This suggests that widespread Ca2+ action potentials were not generated, and any significant [Ca2+] increase depends on somatically triggered Na+ action potentials.

In the visual system of primates, different neuronal pathways are specialized for processing information about the spatial coordinates of objects and their identity - that is, 'where' and 'what'. By contrast, rats and other nocturnal animals build up a neuronal representation of 'where' and 'what' by seeking out and palpating objects with their whiskers. We present recent evidence about how the brain constructs a representation of the surrounding world through whisker-mediated sense of touch. While considerable knowledge exists about the representation of the physical properties of stimuli - like texture, shape and position - we know little about how the brain represents their meaning. Future research may elucidate this and show how the transformation of one representation to another is achieved.

Neural activity in the brain is followed by localized changes in blood flow and volume. We address the relative change in volume for arteriole vs. venous blood within primary vibrissa cortex of awake, head-fixed mice. Two-photon laser-scanning microscopy was used to measure spontaneous and sensory evoked changes in flow and volume at the level of single vessels. We find that arterioles exhibit slow (<1 Hz) spontaneous increases in their diameter, as well as pronounced dilation in response to both punctate and prolonged stimulation of the contralateral vibrissae. In contrast, venules dilate only in response to prolonged stimulation. We conclude that stimulation that occurs on the time scale of natural stimuli leads to a net increase in the reservoir of arteriole blood. Thus, a "bagpipe" model that highlights arteriole dilation should augment the current "balloon" model of venous distension in the interpretation of fMRI images.ocalized changes in the flow and volume of oxygenated blood in the brain are commonly used as a correlate of heightened neural activity. For two important imaging modalities, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) (1) and intrinsic optical signal imaging (IOS) (2), the signals are generated by a complex interplay of the rate of oxidative metabolism, the flux of blood in the underlying angioarchitecture, and changes in vascular volume (3). The locus for the increase in vascular volume that follows sensory stimulation (i.e., arterioles or venules) is an enduring controversy that bears directly on interpreting and quantifying fMRI signals (4-6). To resolve this question, we used in vivo two-photon laserscanning microscopy to image spontaneous and sensory evoked vascular dynamics in the vibrissa area of parietal cortex of awake, head-fixed mice. All data were collected through a reinforced thin-skull window (7) (Fig. 1A); this method obviates potential complications from inflammation or changes in cranial pressure that may occur with a craniotomy (8). ResultsImages of the pial surface and measurements of the diameter of the lumen of surface arterioles and venules were performed while the mouse sat passively (Fig. 1B). Dilations greater than 5% of the baseline diameter occurred with frequencies of 0.07 ± 0.05 Hz (mean ± SD, n = 118 arteries in six mice). The diameters of short segments of arterioles (red in Fig. 1B) exhibited relatively large spontaneous increases in the spectral range between 0.1 Hz and 1 Hz ( Fig. 1 C and D). The peak amplitude of these fluctuations was 23% ± 10% of the initial vessel diameter across all arterioles, with instances of a 50% increases in diameter. Further, these lowfrequency oscillations were strongly coherent and synchronous over a distance of several hundred micrometers across cortex (198 pairs of vessels, in six mice, that were separated by 20-315 μm; slope of coherence = 0.001 μm −1 [nonsignificant (NS)] and slope of phase shift = 0.0009 rad/μm

We present a method to form an optical window in the mouse skull that spans millimeters and is stable for months without inflammation of the brain. This enabled us to repeatedly image blood flow in cortical capillaries of awake animals and determine long-range correlations in speed. We further demonstrate repeated cortical imaging of dendritic spines, microglia, and angioarchitecture, as well as illumination to drive motor output via optogenetics and induce microstrokes via photosensitizers.