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**New preprint from the lab**

Regional, layer and cell-class specific connectivity of the mouse default mode network

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

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)

We previously identified an evolutionary precursors of the DMN in the mouse

👉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

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

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

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

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

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

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

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 👇…

Take-home message for neurobiologists currently investigating mouse PFC, retrosplenial or other DMN regions:

*Your work has more translational value than you (may)

👉You are investigating key substrates of an evolutionary network that can be mapped across species!

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
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