**New preprint from the lab**
Regional, layer and cell-class specific connectivity of the mouse default mode network tinyurl.com/yddanw5w
Conceived & majestically led by @DrJigsaww @harrisjuliea @AllenInstitute
Thread covering DMN basics + implications of findings
1/n 👇
Regional, layer and cell-class specific connectivity of the mouse default mode network tinyurl.com/yddanw5w
Conceived & majestically led by @DrJigsaww @harrisjuliea @AllenInstitute
Thread covering DMN basics + implications of findings
1/n 👇
What is the Default Mode Network (DMN)?
👉Network identified in human PET/fMRI studies
👉Active and strongly synchronized during rest
👉Desynchronized by goal-oriented tasks
👉Encompasses associative cortices - Prefrontal, Cingulate, Retrosplenial, Parietal, Temporal
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👉Network identified in human PET/fMRI studies
👉Active and strongly synchronized during rest
👉Desynchronized by goal-oriented tasks
👉Encompasses associative cortices - Prefrontal, Cingulate, Retrosplenial, Parietal, Temporal
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Why study the DMN?
👉Most prominent large-scale network of human brain
👉Pivotal substrate for higher-order cognitive and social functions
👉Key point of vulnerability for autism, schizophrenia, Alzhemier's and other brain disorders (seminal feature review below)
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👉Most prominent large-scale network of human brain
👉Pivotal substrate for higher-order cognitive and social functions
👉Key point of vulnerability for autism, schizophrenia, Alzhemier's and other brain disorders (seminal feature review below)
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We previously identified an evolutionary precursors of the DMN in the mouse tinyurl.com/y95ra427
👉offers opportunity to manipulate this network and study its wiring diagram
👉neural basis of MDN disruption can be studies in mouse lines modelling human pathology
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👉offers opportunity to manipulate this network and study its wiring diagram
👉neural basis of MDN disruption can be studies in mouse lines modelling human pathology
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Here we asked
👉what is the wiring diagram of the mouse DMN at the *regional* and *cell type* level?
We first used mouse fMRI to anatomically locate DMN in the mouse. We next projected these masks onto new CCFv3 mouse brain @AllenInstitute template
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👉what is the wiring diagram of the mouse DMN at the *regional* and *cell type* level?
We first used mouse fMRI to anatomically locate DMN in the mouse. We next projected these masks onto new CCFv3 mouse brain @AllenInstitute template
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What anatomical regions belong to the mouse DMN?
In keeping with human/primate mapping, mouse DMN largely composed by midline associative cortices, i.e. Cingulate, Prefrontal, Retrosplenial, peri-hippocampal plus visual portions too. Also medio-dorsal thalamus, claustrum
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In keeping with human/primate mapping, mouse DMN largely composed by midline associative cortices, i.e. Cingulate, Prefrontal, Retrosplenial, peri-hippocampal plus visual portions too. Also medio-dorsal thalamus, claustrum
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What is the connectivity profile of the DMN?
Axonal projection data show that DMN regions are tightly interconnected 👉 they form a community
However, higher fraction of outgoing connections than other modules 👉DMN is wired as a associative-integrative network
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Axonal projection data show that DMN regions are tightly interconnected 👉 they form a community
However, higher fraction of outgoing connections than other modules 👉DMN is wired as a associative-integrative network
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Is there a layer-specific architecture within the DMN?
It would actually seem so:
👉DMN L2/3 neurons primarily project *WITHIN* the DMN
👉DMN L5 neurons project to both in-DMN & out-DMN targets i.e. these are likely to sub-serve the associative functions of this network
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It would actually seem so:
👉DMN L2/3 neurons primarily project *WITHIN* the DMN
👉DMN L5 neurons project to both in-DMN & out-DMN targets i.e. these are likely to sub-serve the associative functions of this network
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Can we differentiate DMN neuronal populations based on their targeting profile?
"We" (majestic plural here, all tracing work here and above was done by @DrJigsaww & al...) used intersectional viral labelling to parse DMN neuronal populations based on projection targets
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"We" (majestic plural here, all tracing work here and above was done by @DrJigsaww & al...) used intersectional viral labelling to parse DMN neuronal populations based on projection targets
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Using this method two segregable in- and out-DMN projection neuron types could be identified
Where are these cells located?
👉 In the retrosplenial cortex - i.e. a rodent “precursor” of Posterior Cingulate Cortex (PCC) & key integrator of DMN input/output
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Where are these cells located?
👉 In the retrosplenial cortex - i.e. a rodent “precursor” of Posterior Cingulate Cortex (PCC) & key integrator of DMN input/output
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Notably - these cells can be identified based on their *transcriptomic signature* making them (in principle) amenable to specific targeting in future investigations.
See description of ontology in this amazing @AllenInstitute resources here 👇
biorxiv.org/content/10.110…
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See description of ontology in this amazing @AllenInstitute resources here 👇
biorxiv.org/content/10.110…
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Take-home message for neurobiologists currently investigating mouse PFC, retrosplenial or other DMN regions:
*Your work has more translational value than you (may)
know*
👉You are investigating key substrates of an evolutionary network that can be mapped across species!
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*Your work has more translational value than you (may)
know*
👉You are investigating key substrates of an evolutionary network that can be mapped across species!
12/n
A massive shout out to @ColettaLudovico @adliska for fMRI work in the lab, @ERC_Research (#Disconn) for funding
And check out original thread form @Drjigsaw too, including list of @AllenInstitute contributors
And check out original thread form @Drjigsaw too, including list of @AllenInstitute contributors
