diff --git a/.gitignore b/.gitignore new file mode 100644 index 0000000..e43b0f9 --- /dev/null +++ b/.gitignore @@ -0,0 +1 @@ +.DS_Store diff --git a/README.md b/README.md index aead566..8075abc 100644 --- a/README.md +++ b/README.md @@ -1,8 +1,14 @@ -tags: open, questions, query, projects, lab, collaboration, mind map +--- +title: projects-start +date: 2016-10-06 10:01:10 date original: 2016-05-18 14:18:20 -date: 2016-05-18 15:29:23 -tite: projects-start +author: James Ackman +tags: open, questions, query, projects, lab, collaboration, mind map +--- -This is a private lab repo and wiki for our team to contribute, discuss, and edit questions & goals. -[Go to the wiki](https://github.com/ackmanlab/projects-start/wiki) +This is a local lab repo for our team to contribute, discuss, and edit questions & goals. + +[Go to open questions](questions.md) + + diff --git a/questions.md b/questions.md new file mode 100644 index 0000000..ead666d --- /dev/null +++ b/questions.md @@ -0,0 +1,112 @@ +tags: open, questions, query, projects, lab, collaboration +date: 2016-05-18 14:18:20 +title: projects-start + +Welcome to the projects-start wiki! + +##Questions + +A few queries for the lab. The questions are not listed in any particular order or priority. + +### Experiments + +Many of these require designing and performing new experiments... + +#### Neural activity manipulation + +* Is cortical wave activity the same in pan neuronal gcamp6 vs upper layer gcamp6 mice? What about deeper layers? At all developmental ages? Implications for causative role of spontaneous cortical waves with inter-areal synaptic development? +* Can we manipulate sensory input patterns with DREADDs and see corresponding changes in cortical wave activity (transgenic mouse retinal-cre-DREADDs experiment)? +* Can we manipulate intra-cortical input patterns with DREADDs and see corresponding changes in cortical wave activity (intra cerebral AAV-DREADDs injection experiment)? +* Can we manipulate intra-cortical input patterns with red-shifted optogenetics and see corresponding changes in cortical wave activity? + + +#### Sensory stimulation + +* How does early brain activity predict behavior? Is there a functionally asymmetric activity pattern that predicts lateralized behavior (paw preference)? +* What are the non-mirror symmetric activity patterns between the hemispheres for (trunk limb 'spirals and circles' in the fMOI movies)? + * Are these patterns related to inter-hemispheric feed-forward inhibition? Different flexor/extensor or motor neuron pools? Limb abduction or adduction movement sequences? Is it different in mice with bad balance or locomotion? What about swimming? +* Does abduction (away from body core) and adduction (towards body core) of the forelimbs/paws map to distinct fMOI activation patterns? +* Can we map moving bar stimuli of speeds/frequencies to fMOI in visual cortex in 2-3 wk old mice? +* Can we map auditory frequencies/amplitude to fMOI in auditory cortex in 2-3 wk old mice? + +#### Genes/mouse models + +* Are inter-hemispheric activity patterns and associations different in acallosal mice? What does this tell us about the contribution of inter-hemipheric vs sub-cortical inputs for inter-areal activity correlations? +* Is there something (anything) obviously different about the cortical activity patterns in an autism or schizophrenic mouse model? What model? +* Are immediate early genes (IEG) activated during/between cortical waves in developing mice? If so, which ones? Is there differential activation during sensory input deprivation during development (retinal, cochlear, limb ablations) + + + +#### Environment + +* What does administration of a serotonin-reuptake inhibitor do anything to fMOI cortical wave activity? +* How different is global cortical activity during light isoflurane anesthesia? During ketamine anesthesia? During hypothermia? During tamoxifen injections? + +#### Cortical waves + +* Are cortical wave properties (velocity, wavefront pattern) during development related to topographic discrimination/receptor density (retina/V1 vs whiskers/barrel cortex) mapping of the sensory periphery? +* Is it possible to make transgenic (gcamp6) turtles (make earliest amniote vertebrate model for retinal waves)? + +#### Other + +* Can we image the cerebellum? Is it's activity coordinated with that of isocortex? +* Why does a developmentally regulated correlation between PPC & RSA and limb movement activity exist? Transient synaptic formation/strengthening followed or silencing while waiting for behaviorally relevant sensation/decision making to occur? What brain areas do they 'talk to' during development? +* Does the classic monocular deprivation/ocular dominance shifting experiments in P20-P28 mice do anything to global inter- or intra-cerebral fMOI activity patterns? +* Is there a 'phantom limb' activity pattern in mice after limb ablation? Is there increased co-activation with pain/body core areas (cingulate,retrosplenial cortex)? Is it different/better at earlier ages? Can it be reversed? + + +#### Ephys, Behavior + +* Are fMOI cortical wave patterns strongly associated with different EEG/LFP frequencies (delta, alpha, theta, gamma) during different behavioral states in 2-3 wk old mice? +* Can we perform cell attached blind patch clamp recordings simultaneously with fMOI? +* Can we see paw preferences in 2-3 week old mice? +* Can we measure optokinetic response behavior in 2-3 week old mice? +* Can we measure water maze/visual acuity behavior tracking on 2-3 week old mice? +* Can we detect evidence for any kind of reverbatory wave 'memory' trace from a recently experienced event (a multimodal aversive or rewarding stimulus (air puff, drop, shaking, swimminmg)? a **moving** looming object in space (vision +/- sound) in a particular direction?) in developing mice? +* Can we perform coupled imaging of two animals with realtime activity or behavioral detection and sensory feedback on the rig? Can this be used to social/behavorial development (can we make friendly/outgoing vs aggressive mice? Ones that prefer or are aversive to tactile vs visual vs auditory vs olfactory cues)? Does this cause changes in the strength of synaptic connections and later behavioral preferences? Can these changes then be reversed or is there a 'critical period'? + + +#### Cellular development + +* Do retinal waves influence glial development? Do microglia mediate the effects of retinal waves on synaptic development? +* Do retinal waves influence interneuron migration/maturation during early postnatal development? +* Are retinal waves utilized for callosal projection targeting of axons? +* Are there any evidence for interareal functional connections that are active early in development during any or all behavioral states then become silent? Implications for selectionist vs constructionist learning paradigms across cell assemblies? + + + + +### Analyses + +Many of these can be answered by doing new analyses on existing data... + +#### waves + +* Do retinal waves regulate motor activity (are developing mice more likely to 'wake up' at the beginning or ending of a retinal wave)? + * Could this be important for wiring together and preparing circuitry necessary for innate visual behavior (e.g. linking visual responses such as a moving shadow from an owl in the sky to attention/motor action)? +* Which brain areas are active during retinal waves with PSTH analysis? Wave form average? +* Do retinal waves drive higher order cortical areas? +* Is there an area in M2/cingulate like the FEF/FOF (frontal eye/orienting field) that is active around retinal waves at any particular age? Does this argue for a strength of fMOI in analysing global inter- vs intra- cerebral functional activity patterns? +* Does the similarity of retinal wave activation between the superior colliculus and V1 increase during development? Does the failure rate of wave front propagation decrease? +* Does the velocity of manually observed cortical waves match that of computed with that with optical flow/computer vision techniques? + + +#### function + +* Can clustering/pca break joint cortical activity/body motion movies into distinct (or possibly overlapping) behavioral states? +* Do global activity patterns cluster into distinct components based on behavioral state (e.g. quiet sleep, active sleep, wakefulness)? +* What are global cortical wave patterns for-- do they cluster into different motifs during different behavioral states or sensory activations? Can they represent functionally associated, **inter-areal cell assemblies**? +* In what fraction of our videos can we see whisker/mystacial pad movements? +* How well can we see eye movements in our existing videos? +* Can we identify jaw movements in our existing videos? +* Which regions are active around limb movements with PSTH analysis? Wave form average? + + +#### connectivity + +* What fraction of other Allen connectivity atlas isocortex regions (besides VISp) have particular long distance intra-cerebral connection patterns? +* Which brain regions are 'driver nodes' (high eig centrality, low betweeness centrality)? Does it change during development? +* Are cortical hubs from fMOI association matrices the same as those predicted by the Allen connectivity atlas? +* Are cortical activity maps from fMOI similar to those of structural connection patterns from the Allen Brain atlas? +* Does a finer grain/higher density ROI analysis of the cortical association matrix give a similar number and membership of network modules? +