1/ Very excited to announce the 🚨 #tweeprint 🚨 for our new paper "Cortical integration of higher-order thalamic inputs is lineage-dependent" - check it out here biorxiv.org/content/10.110… #biorxiv_neursci or read on for some serious devneuro/systems crossover mashup...
2/ Sensory processing requires that the brain is able to integrate info about a stimulus with info that reflects the context in which it was experienced. In the cortex, the major sources of these types of info are the first-order (sensory) and higher-order (context) thalamus
3/ Higher-order inputs, in particular, have been implicated in several fundamental cognitive processes like attention, plasticity and conscious perception, and are known to shape the sensory response properties of cortical neurons
4/ Interestingly, we've known for a while that some cortical neurons are more likely to receive higher-order input than others (i.e. some neurons get more contextual info) but we don't understand what decides which neurons are the chosen ones. 
5/ In part, the reason this is still unclear is because the cortical circuits set up to receive thalamic inputs in the adult brain are hugely complicated, defined by precise patterns of synaptic connectivity between diverse neuronal cell types.
6/ Much of this complexity is established during embryonic development, where cortical neurons are born from a heterogeneous population of neuronal progenitor cell types. (see sciencedirect.com/science/articl…)
7/ Previous work from our lab (nature.com/articles/s4146…) found that the local connections between cortical neurons reflects their lineage (i.e. the progenitor type they derive from)
8/ But it's unclear whether lineage represents a more general organisation framework for sensory processing circuits - including those between cortex and thalamus.
9/ Here biorxiv.org/content/10.110… we examine how lineage relates to the thalamic inputs received by cortical neurons, by performing longitudinal studies that allow us to relate the properties of adult neurons to the progenitors from which they derive during embryonic development.
10/ L4 of mouse S1 is the perfect system to address this question, because the thalamic inputs from the relevant first-order (VPM) and higher-order (POm) nuclei are exquisitely organised into a somatotopic representation of the whiskers - so called barrels and septa.
11/ Using a combo of in utero labelling, functional anatomy and in vitro/in vivo ephys, we characterised L4 neurons derived from a population called apical intermediate progenitors (aIP-derived) and compared them to L4 neurons derived from other progenitors (OP-derived)
12/ We found that aIP-derived neurons exhibit multi-whisker response properties and tend to target the areas outside of barrels with their dendrites, consistent with the sampling of inputs from the higher-order thalamic nuclei, POm
13/ To test this directly, we performed dual patch-clamp recordings from pairs of aIP- and OP-derived L4 neurons. This confirmed that aIP-derived neurons do indeed receive greater input from POm compared to OP-derived neurons.
14/ Next, we wanted to understand more about what mechanism might be responsible for this. So we quantified the expression of Lhx2, a transcription factor known to play a role in S1 circuit formation, and found that aIP-derived neurons express low endogenous levels of Lhx2.
15/ When Lhx2 expression was increased, aIP-derived neurons exhibited single-whisker response properties, became more likely to target barrels with their dendrites, and received fewer higher-order inputs from POm
16/ Finally, we wanted to explore the functional consequences of this. As I mentioned above, higher-order inputs are known to play a pivotal role in the induction of sensory-evoked plasticity in the cortex (see nature.com/articles/natur…)
17/ We found that the loss of higher-order inputs to aIP-derived L4 neurons was sufficient to disrupt the induction of sensory-evoked plasticity
18/ Thus we describe a lineage-dependent mechanism by which higher-order thalamic inputs are integrated and processed within cortex.
19/ It seems that the evolutionary emergence of different progenitor types does not just serve to expand cortical volume, or the diversity of neuronal cell types, but organises cortical circuits to receive specific types of thalamic input.
20/ This generates distinct routes for information flow through the adult cortex and represents a new approach to investigating the cortical mechanisms underlying sensory perception.
21/ A massive thank you to everyone involved with this huge body of work. Akerman lab members past and present @TommasEllender @Joranium @gsgothard, and those who have given invaluable feedback at various stages of this project and my PhD more generally @paqio @ZoltanMolnar64
22/ Thanks also to @ChCh_Oxford and Clarendon for funding me along the way, and @ERC_Research @BBSRC for funding this research
23/ Generally, I hope that this work will encourage taking a developmental view of more complex problems in sensory/systems neuro, towards the establishment of cortical development as a viable therapeutic window. But for now...
I should also say that I’m looking forward to presenting this work @corticaldev2020 - can’t wait for the return to conferencing IRL
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