From dd9f3eb0fe549491bf8559658bd593610b82c70d Mon Sep 17 00:00:00 2001 From: ackman678 Date: Mon, 14 Jul 2014 12:30:31 -0400 Subject: [PATCH] res1 work --- wholeBrain_main.md | 20 ++++++-------------- 1 file changed, 6 insertions(+), 14 deletions(-) diff --git a/wholeBrain_main.md b/wholeBrain_main.md index 0fd0bab..87a1c1d 100644 --- a/wholeBrain_main.md +++ b/wholeBrain_main.md @@ -22,21 +22,11 @@ Brain development requires neural activity and calcium dynamics for establishing ## Ongoing activity in developing neocortex is characterized by discrete domains -We performed transcranial optical recordings from mice expressing the genetic calcium reporter GCaMP (GCaMP3 or GCaMP6) throughout cortical neurons to assess neural population activity patterns with mesoscopic spatial and temporal resolutions (10s of microns and 100s of milliseconds) at macroscopic scale (millimeters). We performed our recordings in three age groups during the first two postnatal weeks during which the mouse brain develops to >90% of its adult weight [#Kobayashi:1963]: P2-P5, P8-P9, and P12-13. Functional mesoscale optical imaging (fMOI) revealed that supracellular cortical activity patterns were characterized by discrete domains of activation (Fig. 1a-c) [Supplementary Movie 1](../wholeBrain_blob/ackmanWholeBrainGcampP3.mov). These activity domains ranged from 250 - 976 µm in diameter and 0.4 - 2.6 s in duration (Table 1.) (*Ns*, Fig. 1e-h). +We performed transcranial optical recordings from mice expressing the genetic calcium reporter GCaMP (GCaMP3 or GCaMP6) throughout cortical neurons to assess neural population activity patterns at macroscopic scale (millimeters) and with mesoscopic spatial and temporal resolution (10s of microns and 100s of milliseconds). We performed our recordings in three age groups during the first two postnatal weeks during which the mouse brain develops to >90% of its adult weight [#Kobayashi:1963]: P2-P5, P8-P9, and P12-13. -The duration of domain activations was not significantly affected by age (F = 0.933, p = 0.428, r^2 = 0.00567) or by hemisphere (F = 0.017, p = 0.900) (P2-5, N = 15653; P8-9, N = 70189; P12-13, N = 120214 domains) (Fig. 1e,f). +Functional mesoscale optical imaging (fMOI) revealed that supracellular cortical activity patterns were characterized by discrete domains of activation (Fig. 1a-c) [Supplementary Movie 1](../wholeBrain_blob/ackmanWholeBrainGcampP3.mov). These activity domains ranged from 250 - 976 µm in diameter and 0.4 - 2.6 s in duration (Fig. 1e-h) (Table 1.) . The duration of cortical domain activations was not significantly affected by age (F = 0.933, p = 0.428, r^2 = 0.00567) or by hemisphere (F = 0.017, p = 0.900) (P2-5, N = 15653; P8-9, N = 70189; P12-13, N = 120214 domains) (Fig. 1e,f). There was a significant effect of age on the diameter of cortical domain activations (F = 25.788, p = 0.000188, r^2 = 0.1277), but not hemisphere (F = 0.192, p = 0.671808) (Fig. 1g,h). The frequency with which cortical domain activations occurred increased with age (F = 29.562, p = 8.86e-12, r^2 = 0.2535) and did not differ significantly between the hemispheres (F = 0.012, p = 0.911) (P2-5, N = 22; P8-9, N = 30; P12-13, N = 38 movies/hemi) (Fig. i,j) (Table 1). -There was a significant effect of age on the diameter of cortical domain activations(F = 25.788, p = 0.000188, r^2 = 0.1277), but not hemisphere (F = 0.192, p = 0.671808) (Fig. 1g,h). - -Cortical calcium domain frequency significantly increased with age (F = 29.562, p = 8.86e-12, r^2 = 0.2535) and did not differ significantly between the hemispheres (F = 0.012, p = 0.911) (P2-5, N = 22; P8-9, N = 30; P12-13, N = 38 movies/hemi) (Fig. 1i,j). - -The neocortex exhibits a characteristic modular organization across the cortical surface such that vertical arrays of cells concerned with specific sensory features are grouped together as columns in a topographic fashion [#Mountcastle:1997]. Most evidence to date suggests that cortical columns range from 300-600µm diameter, even between species whose brain volumes differ by a factor of 10^3 [#Mountcastle:1997]. - -We parcellated the brain into distinct anatomical boundaries by using reference coordinates from a mouse line that expressed the tdtomato reporter in thalamocortical afferents (Fig. 1c,d). Patterns of thalamocortical axon terminal can be used to parcellate out areal boundaries of primary sensory cortical areas [wong riley 1979]. We matched these parcellations to a Allen brain atlas adult mouse reference image and than linearly scaled the remaining parcellations in our FOV on to the images of our recordings that contain functional boundaries (like in the domain centroid activation plot and in the domain frequency maps). - -Longer duration domains of activation occurred in the visual cortex and motor cortex (*Ns*, Fig. 2b,c). In the second postnatal week the size of cortical activity domains became larger in the frontal-motor and S1-limb/body regions [Supplementary Movie 2](../wholeBrain_blob/ackmanWholeBrainImaging-lo.mov). - -There were longer activations on the order of seconds to tens of seconds in visual cortex driven by retinal waves [#Ackman:2012]. Long lasting wave-like activations also occured in motor cortex P2-5 (Fig 2 montage). +The neocortex exhibits a characteristic modular organization across the cortical surface such that vertical arrays of cells concerned with specific sensory features are grouped together as columns in a topographic fashion [#Mountcastle:1997]. Most evidence to date suggests that cortical columns range from 300-600µm diameter, even between species whose brain volumes differ by a factor of 10^3 [#Mountcastle:1997]. Its intriguing that we found the size of cortical domains to be centered on this range at early ages, because this is in agreement with previous work showing that population activity in neonatal rat barrel cortex maps onto ontogenetic modules centered on each barrel column [#Yang:2012a] and barrels are an archetypical model for columnar cortical function in rodent. Indeed, we found a cortical area in primary somatosensory cortex at P2-5 where cortical domain activations group into rows and individual modules that match primary barrel cortex structure (Fig. 1c) (Supplementary Fig.). This indicates that early cortical activity in some cortical areas is matched to the size the functional cortical modules that are thought to be the fundamental procdessing unit of the cerebral cortex. ![ **Figure 1.** Calcium domains throughout neonatal mouse neocortex. **a** Experimental schematic. **b** Single image frame showing calcium domains in both hemispheres at postnatal day 3 (P3) and automatically detected domain masks. **c** Centroid positions for segmented domain masks from a 10 min recording. Points are overlaid on a reference map of primary sensory areas determined by thalamocortical inputs (red outlines). Notice rows of whisker barrels are evident in the structure of domain centroid positions. **d** Functional activity map at P3. Based on pixel activation frequency from all detected domains in a single 10 min recording. Map is overlaid on cortical areal parcellations. Notice localized maxima and minima of functional activity between areas that approximate known anatomical cortical area boundaries and the mirroring of map structure bilaterally. **e** Mean domain duration maps from 3 SNAP25-Ai103 mice. **f** Histograms showing domain durations distributions in the P2-5, P8-9, and P12-13 age groups and by cortical hemisphere (L, R). **g** Mean domain diameter maps from same 3 mice in e. **h** Histograms showing the distributions of domain diameters. **i** Mean domain frequency maps from same 3 mice in e. **j** Boxplot distributions of hemispheric domain frequencies.](figure1.png) @@ -51,13 +41,15 @@ There were longer activations on the order of seconds to tens of seconds in visu [ **Table 1: Domain statistics**] +We examined how the spatiotemporal properties of cortical domains vary among different cortical regions by parcellating the brain into distinct anatomical boundaries using reference coordinates from a mouse line that expressed a tdtomato reporter in thalamocortical afferents at P7 (Fig. 1c,d) (Supplementary Fig.). Patterns of thalamocortical axon terminals can be used to map out areal boundaries of primary sensory cortical areas [wong riley 1979]. We matched these parcellations to a Allen brain atlas adult mouse reference image and than linearly scaled the cortical area reference boundaries for each animal to maps containing functional boundaries for barrel cortex and visual cortex where spontaneous retinal waves functionally map out developing visual areas [#Ackman:2012] (Fig. 1c-e,g,i). + +Cortical domain frequency among different regions scaled as a function of net cortical area and this association became stronger during the course of development (Fig. 2a). The overall frequency of activity was remarkably uniform across cortical areas at eah age of devloepment (Supplementary Fig). The most frequently cortical regions at each age group when normalized to the amount of total amount of coritcal space was the limb/trunk representations in somatosensory cortex (Fig. 1i, Supplementary Fig.). The long tails in the domain duration and diameter distributions at P2-5 adn P8-9 (Fig. 1f,h) were dominated by retinal wave driven cortical activity in V1 that lasted on the order of seconds to tens of seconds (Fig. 1e, Fig. 2b,c), but also by long lasting wave-like activations occurring in motor cortex (Fig. 1e, Fig. 2b,c). In the second postnatal week the size of cortical activity domains became larger in the frontal-motor and S1-limb/body regions [Supplementary Movie 2](../wholeBrain_blob/ackmanWholeBrainImaging-lo.mov) (Fig. 2d). ![ **Figure 2.** Spatiotemporal characteristics of cortical domains. **a** Domain frequency as function of cortical area size. **b** Scatterplots of domain diameter and duration. **c** Time projection color maps of waves in visual cortex and motor cortex at P5. **d** Time projection color maps of interareal activations at P13. **e** Scatterplots of wave motion index as function of domain diameter. **f** Mean wave motion index over development.](figure2.png) - ## Cortical domain activity is state dependent * Previously demonstrated that general anesthesia abolishes spontaneous activity in visual system [#Ackman:2012].