fig work

wholeBrain_main.md

@@ -26,6 +26,7 @@ We performed transcranial optical recordings from mice expressing the genetic ca
 
 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 <!--(10-90th percentiles)-->(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).
 
+
 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 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. 
 
 
@@ -40,6 +41,7 @@ The neocortex exhibits a characteristic modular organization across the cortical
 | Notes: Values are reported as medians (median absolute deviation) ||||
 [ **Table 1: Domain statistics**]
 
+## Domain activity dynamics varies among cortical regions
 
 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). 
 
@@ -52,11 +54,11 @@ Cortical domain frequency among different regions scaled as a function of net co
 
 ## Cortical domain activity is coordinated with motor behavior
 
-Next we assessed mesoscale cortical activity patterns as a function of physiological state and motor behavior. It has previously been demonstrated that general anesthesia abolishes spontaneous retinal wave activity in visual system [#Ackman:2012]. We found that during anesthesia induction, there is rapid (<60 s) knock down of cortical activity (Supplementary Movie) (Supplementary Fig) at all ages. While in neonates, no cortical activity was found during general anesthesia in neonates, at P12-13 we found altered spontaneous patterns, with short duration, large diameter population activities synchronizing multiple cortical areas. (Supplementary Movie)
+Next we assessed mesoscale cortical activity patterns as a function of physiological state and motor behavior. It has previously been demonstrated that general anesthesia abolishes spontaneous retinal wave activity in visual system [#Ackman:2012]. We found that during anesthesia induction, there is rapid (<60 s) knock down of cortical activity (Supplementary Movie) (Supplementary Fig) at all ages. While in neonates, no cortical activity was found during general anesthesia, at P12-13 within ~10-20min after general induction we found altered spontaneous patterns, with short duration, large diameter population activities synchronizing multiple cortical regions. (Supplementary Movie)
 
-Variation in the strength of correlation between cortical areas and the motor movement signal depended on brain region (p < 2.2e-16, anova) and age (p = 1.627e-05, anova)  The first age group in which motor cortex exhibited signficant positive correlation with motor movements was at P12-13 (r=0.06±0.02, p-value = 0.001449, t-test).
+We monitored motor movements simultaneously with cortical activity during our fMOI recordings to gain insight into the relationship between motor behavior output to cerebral cortical dynamics during development. The highest levels of synchronized cortical domain activity occurred during periods of relatively sparse motor behavior whereas the lowest levels of synchronized cortical activity occurred during periods of increased motor movement (Fig. 3c-e). Variation in the strength of correlation between cortical areas and the motor movement signal depended on both brain region (p < 2.2e-16, anova) and age (p = 1.627e-05, anova) (Fig 3c-f). Interestingly, the first age group in which motor cortex exhibited signficant positive correlation with motor movements was at P12-13 (r=0.06±0.02, p-value = 0.001449, t-test) (Fig. 3f).
 
-![ **Figure 3**. Cortical domains are state dependent. **a** Experimental schematic. Red light illumination measured with a photodiode (PD) was used to monitor motor activity. **b** Cortical activity (active fraction) in each hemisphere after onset of gas anesthetic. **c** Cortical activity and coincident motor activity signals. Gray shading indicates active and quiet motor periods determined by the half-rise and decay times from peak in the low pass filtered motor signal. Active pixel fraction traces for motor (M1,M2), somatosensory (HL,FL,T; barrel), and visual (V1,V2) cortex shown at bottom of panel. Red links show synchronized motor movements and brain activity with different cortical regions. **d** Single frame domain masks for times indicated in **c**. **e** Pixel activation frequency maps during quiet and active motor periods. **f** Cross-correlation functions between cortical regions and motor movement signals. Notice the general negative correlation between motor activity and all cortex activity signals (r = , p = ) and the high positive correlation between motor and S1-limb/body signals (r = 0.3019, p < 2.2e-16).](figure3.png)
+![ **Figure 3**. Cortical domains are state dependent. **a** Experimental schematic. Red light illumination measured with a photodiode (PD) was used to monitor motor activity. **b** Cortical activity (active fraction) in each hemisphere after onset of gas anesthetic. **c** Cortical activity and coincident motor activity signals. Gray shading indicates active and quiet motor periods determined by the half-rise and decay times from peak in the low pass filtered motor signal. Active pixel fraction traces for motor (M1,M2), somatosensory (HL,FL,T; barrel), and visual (V1,V2) cortex shown at bottom of panel. Red links show synchronized motor movements and brain activity with different cortical regions. **d** Single frame domain masks for times indicated in **c**. **e** Pixel activation frequency maps during quiet and active motor periods. **f** Cross-correlation functions between cortical regions and motor movement signals. Notice the general weak correlation between motor movement and all cortical activity signals (r = , p = ) and the high positive correlation between motor movement and S1-limb/body signals (r = 0.3019, p < 2.2e-16).](figure3.png)
 
 
 ## Cortical activity is mirrored between the hemispheres