Added some outline and background info to readme. Small changes to intro. and results text1. Outline conclusions.
Introduce through context of Mountcastle/Hubel Wiesels somatosensory and visual cortical column organization. All these indicate that columns/hyper/macro columns are 300-500µm diameter across species.
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ackman678
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README.md
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README.md
@@ -12,6 +12,8 @@ The idea is to provide a clear and beautiful representation of the visualized ac
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### Scientific importance
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A comprehensive description of the spatiotemporal activity patterns in the immature brain will be crucial to understanding the developmental dynamics that exist between intrinsic and extrinsic factors that regulate circuit development.
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Indeed one of the fundamental goals of the BRAIN Initiative funded by NIH, NSF, and DARPA is provide dynamic maps of the brains electrical activity at an intermediate scale that bridges the local and global assessments garnered through current technologies in animals and humans. [NIH BRAIN working group interim report](http://acd.od.nih.gov/ACD-BRAIN-Working-Group-Report.pdf)
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* signature patterns that predict current or future behavior
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* construction of self-organizing circuits (advanced robotics -- *Terminators, Skynet, & Cylons!*)
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@@ -56,6 +58,62 @@ For example:
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* Aberrant activity patterns in developmental disorder and seizure models?
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## Outline
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### Intro or conclusion stuff
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- Neural activity, drugs, and birth defects
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- epilepsy
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- autism
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- What is the activity?
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- instructive or permissive?
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- leinekukel and khazipov work [#Leinekugel:2002][#Khazipov:2004a]
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- ucla konnerth imaging work [#Golshani:2009][#Adelsberger:2005]
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- human occipital cortex and retinal wave paper [#Vanhatalo:2005][#Tolonen:2007][#Ackman:2012]
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- To understand the informational capacity of neural activty in the developing brain, the structural dynamics of persistent activity must be understood.
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- completely random? Organized in space and time, and at what scale?
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- previous work on interneuron migration, axon growth (olavarria work) synaptic formation, and anatomical studies indicates significant development decisions are being made in first postnatal week
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### Ongoing activity in developing isocortex is characterized by discrete domains
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* Cortical column (mini/meso/super columns) history (20th century anatomists-- sherrington, valverde, rakic, etc).
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* Column physiology-- Hubel and Wiesel. Rodent V1?
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* Developmental studies-- fetal monkey ODCs.
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* Rodent barrels (early anatomical emergence from TC input, functional/physiological emergence?).
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* What is known about columns/domains in secondary/association/non-primary sensory representations? Rest of rodent S1 (non-barrel cortex?).
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* Calcium domains of Yuste, Science 1992 paper. [#Yuste:1992]
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* Other slice calcium recordings, patch/gap junctions. In vivo physiology? (Not too many multisite electrode recordings in cortex, spatial resolution issue).
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* Calcium imaging-- Konnerth 'waves' in Ent cortex [#Adelsberger:2005]. For visual cortex, domains activity in extrastriate cortex (Ackman Nature 2012). But S1-- [#Golshani:2009] work in later postnatal-- but activity not obeying domains in barrel cortex-- problem with spatial sampling in the xy and the z for this study?
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### Cortical domain activity is state dependent
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* EEG slow oscillations not detectable until P10 in rodent.
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* Previously demonstrated that general anesthesia abolishes spontaneous activity in visual system [#Ackman:2012].
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* What about ongoing activity in other cortical areas during early brain development? Surgical procedure relevance.
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* No population calcium activity found during gen'l anesthesia, only slow traveling waves.
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* During anesthesia induction, rapid (<30 s) knock down of discrete domain activity (P3 mouse <120518_09.tif>). Cingulate, retrosplenial activations the last to go-- default mode/resting state network areas last.
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<120518_09_mjpeg.mov>
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### Cortical activity is mirrored between the hemispheres
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* Inter hemispheric functional connectivity, importance for autism, schizophrenia. Maybe an activity-dependent mechanism for commisural connectivity.
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* olavarria work, evidence for inter hemispheric activity dependence
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* [#Hanganu:2006], 30% of spindle bursts correlated across hemispheres
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* Activity correlated in anterior-posterior and medial-lateral directions
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* Mirror symmetric and non-mirror symmetric patterns
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* Regional effects, more corr anticorr in certain regions?
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* State dependent corr?
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### Conclusions
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* **Ongoing activity in developing cortex is not random**-- specifically coordinated in space and time within and among cortical areas between the hemispheres
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* BRAIN initiative
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- this work aids at least a couple of the 9 preliminary aims of the Brain project
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* template for assessing altered functional dynamics in models for neurological disorders
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## Workflow
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Writing workflow will be similar to that used previously for [current opinion review][id3]. Some useful info in [currOpinRvw outline][id2].
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@@ -249,6 +249,11 @@
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[#Katz:1996]: Katz, L. C. and Shatz, C. J. (1996). Synaptic activity and the construction of cortical circuits, Science, 274(5290), 1133-8
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[#Mountcastle:1957]: Mountcastle, V. B. (1957). Modality and topographic properties of single neurons of cat's somatic sensory cortex, J Neurophysiol, 20(4), 408-34
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[#Mountcastle:1997]: Mountcastle, V. B. (1997). The columnar organization of the neocortex, Brain, 120 ( Pt 4)(), 701-22
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[#Horton:2005]: Horton, J. C. and Adams, D. L. (2005). The cortical column: a structure without a function, Philos Trans R Soc Lond B Biol Sci, 360(1456), 837-62
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@@ -17,29 +17,21 @@ The cerebral cortex exhibits spontaneous and sensory evoked patterns of activity
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<!--- This should be one paragraph. Some of this intro material could be combined with intro or concl sentences in abstract for a Nature letter (should be referenced and up to 300 words; 200 words preferred) --->
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Brain development requires neural activity and calcium dynamics for establishing proper circuit structure and function. The importance of neural activity in the prenatal and neonatal period can be easily recognized in children exposed to chemical agents affecting neurotransmission during the fetal period that result in severe brain malformations, epilepsy, and mental retardation. Indeed, embryonic limb movements in species ranging from chick to human are thought to be initiated by spontaneous motor neuron activity in the spinal cord and is thought to be crucial for activity-dependent development of motor synapses [Schoenberg:2003] [Marder,Lichtmann]. However it is only recently that we have begun to appreciate the underlying patterns of persistent neural activity that in fact exist in the developing brain in vivo. For example, sensori-motor feedback associated with spontaneous movement generated by spinal motor neurons triggers synchronized 'spindle-burst' potentials among cells in somatosensory cortex [Yang:2009][Khazipov:2004a] before the start of locomotion and tactile behavior. Correlated bursts of activity occur in the developing rat hippocampus in vivo [#Leinekugel:2002] [Mohns&Blumberg]. Spontaneous retinal waves drive patterned activation of circuits throughout immature visual system before the onset of vision [#Ackman:2012] [Hanganu,Colonnese?]. Furthermore, prenatal EEG recordings have demonstrated spindle burst oscillations and slow activity transients in the human infant somatosensory and occipital cortices before birth [#Vanhatalo:2005][#Tolonen:2007]. However, a comprehensive account of the structural dynamics of persistent activity throughout the developing isocortex in vivo has not been undertaken.
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Brain development requires neural activity and calcium dynamics for establishing proper circuit structure and function. The importance of neural activity in the prenatal and neonatal period can be easily recognized in children exposed to chemical agents affecting neurotransmission during the fetal period that result in severe brain malformations, epilepsy, and mental retardation. Indeed, embryonic limb movements in species ranging from chick to human are thought to be initiated by spontaneous motor neuron activity in the spinal cord and thought to be crucial for activity-dependent development of motor synapses [Schoenberg:2003] [Marder,Lichtmann]. However it is only recently that we have begun to appreciate the underlying patterns of persistent neural activity that in fact exist in the developing brain in vivo. For example, sensori-motor feedback associated with spontaneous movement generated by spinal motor neurons triggers synchronized 'spindle-burst' potentials among cells in somatosensory cortex [Yang:2009][Khazipov:2004a] before the start of locomotion and tactile behavior. Correlated bursts of activity occur in the developing rat hippocampus in vivo [#Leinekugel:2002] [Mohns&Blumberg]. Spontaneous retinal waves drive patterned activation of circuits throughout immature visual system before the onset of vision [#Ackman:2012] [Hanganu,Colonnese?]. Furthermore, prenatal EEG recordings have demonstrated spindle burst oscillations and slow activity transients in the human infant somatosensory and occipital cortices before birth [#Vanhatalo:2005][#Tolonen:2007]. Nonetheless, a comprehensive account of the structural dynamics of persistent activity throughout the developing isocortex in vivo has not been undertaken.
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- Neural activity, drugs, and birth defects
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- epilepsy
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- autism
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- What is the activity?
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- instructive or permissive?
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- leinekukel and khazipov work [#Leinekugel:2002][#Khazipov:2004a]
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- ucla konnerth imaging work [#Golshani:2009][#Adelsberger:2005]
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- human occipital cortex and retinal wave paper [#Vanhatalo:2005][#Tolonen:2007][#Ackman:2012]
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- To understand the informational capacity of neural activty in the developing brain, the structural dynamics of persistent activity must be understood.
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- completely random? Organized in space and time, and at what scale?
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- previous work on interneuron migration, axon growth (olavarria work) synaptic formation, and anatomical studies indicates significant development decisions are being made in first postnatal week
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# Results
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## Ongoing activity in developing isocortex is characterized by discrete domains
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## Ongoing activity in developing neocortex is characterized by discrete domains
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* Cortical column (mini/meso/super columns) history (20th century anatomists-- sherrington, valverde, rakic, etc).
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Neocortical organization consists of cortical modules tiled across the cortical surface in a topographic fashion such that vertical arrays of cells concerned with specific sensory features are grouped together as columns [#Mountcastle:1997]. Most evidence to date suggests that columns/hyper/macro columns are 300-500µm diameter across species.
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* Cortical column (mini/hyper columns) history (20th century anatomists-- Lorente de No, Mountcastle, Hubel & Wiesel, rakic, etc).
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* Column physiology-- Hubel and Wiesel. Rodent V1?
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* Developmental studies-- fetal monkey ODCs.
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* Rodent barrels (early anatomical emergence from TC input, functional/physiological emergence?).
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@@ -53,7 +45,7 @@ Brain development requires neural activity and calcium dynamics for establishing
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metric | mean | min | max | unit
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------------- | ----- | ---- | ------ | --------------------
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diameter | 396.0 | 22.7 | 2383.5 | µm
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diameter | 396.0 | 22.7 | 2383.5 | µm
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duration | 0.6 | 0.2 | 14.6 | s
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frequency | 2.9 | | | domains/sec/hemisphere
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[**Table 1: Domain statistics**]
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@@ -63,7 +55,7 @@ frequency | 2.9 | | | domains/sec/hemisphere
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## Cortical domain activity is state dependent ##
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## Cortical domain activity is state dependent
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* EEG slow oscillations not detectable until P10 in rodent.
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* Previously demonstrated that general anesthesia abolishes spontaneous activity in visual system [#Ackman:2012].
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@@ -99,7 +91,7 @@ lenActvFraction>0 | fracCorr | timeCorr_s | fracCorrPos | timeCorrPos_s | fracCo
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## Cortical activity is mirrored between the hemispheres ##
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## Cortical activity is mirrored between the hemispheres
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* Inter hemispheric functional connectivity, importance for autism, schizophrenia. Maybe an activity-dependent mechanism for commisural connectivity.
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* olavarria work, evidence for inter hemispheric activity dependence
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@@ -118,6 +110,15 @@ lenActvFraction>0 | fracCorr | timeCorr_s | fracCorrPos | timeCorrPos_s | fracCo
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**Conclusions:** So the activity in both hemispheres at postnatal day 3 (P3) clearly exhibits significant spatial correlations in both in the medial-lateral and anterior-extent. This is consistent with and complementary to the fact that the active pixel fraction in each hemisphere exhibits a strong temporal correlation as I found earlier in this report [Temporal correlation of activity][]. The medial-lateral positional correlation is stronger than the anterior-posterior (higher *R* and lower *p* value). The total number of coactive frames is `numel(y1(~isnan(y1)&~isnan(y2)))` == **1114 frames**. This is accounts to **37.13%** of the movie or **222.8 s**. Cortex.L had 1635 actvFrames and cortex.R had 1677 actvFrames which means that each hemisphere was coactive with the other hemisphere 1114/1635 == **68.13%** and 1114/1677 == **66.43%** of the active time respectively.
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# Conclusions
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* **Ongoing activity in developing cortex is not random**-- specifically coordinated in space and time within and among cortical areas between the hemispheres
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* BRAIN initiative
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- this work aids at least a couple of the 9 preliminary aims of the Brain project
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* template for assessing altered functional dynamics in models for neurological disorders
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<!--- # References --->
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<<[references.txt]
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