Twitter | Pretraživanje | |
Marco Bocchio
1/ time! If you are interested in , and developmental mechanisms of neural circuit function, check out our new preprint “Hippocampal hub neurons maintain unique functional properties throughout their lifetime”
The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating...
bioRxiv bioRxiv @biorxivpreprint
Reply Retweet Označi sa "sviđa mi se" More
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
2/ Ten years ago, the Cossart lab discovered that rare GABAergic neurons are able to orchestrate single-handedly network dynamics in the CA3 region of the hippocampus . As these cells showed a remarkably high functional connectivity, they were termed ‘hub cells’.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @PicardoMichel @GordFishell
3/ A few years later, and others in the lab (in collaboration with lab) found that many hub cells were GABA cells born early in embryogenesis (thus termed ‘early-born GABA cells’ or ‘ebGABAs’).
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
4/ We asked the following questions: 1. Are ebGABAs hub cells only in CA3 or throughout the hippocampus? 2. Are they hubs at the neonatal stage because they are more mature? Or this is due to a predermined program? 3. Do they remain distinct from other interneurons in adulthood?
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
5/ We tested these questions in the CA1 region because CA1 circuits are well understood, and also because it is more accessible for in vivo calcium imaging. We used a Dlx1/2CreER;GFP line and administered tamoxifen at embryonic day E7.5 to tag the earliest born GABA cells.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
6/ First, we used large-scale calcium imaging in neonatal slices combined with stimulation ebGABAs using whole cell patch clamp. We found that stimulation of a single ebGABA (but not of random GABA cells) could modulate the network. Thus, ebGABAs exert a hub function even in CA1.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
7/ We then examined ebGABAs in adulthood. Using immunohistochemical analysis and reconstruction of biotin-filled cells, we found that ebGABAs aren’t canonical interneurons. They express markers of long-range projecting cell types that target different brain areas.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
8/ EbGABAs' firing patterns ex vivo appear more similar to pyramidal cells than interneurons, with strong adaptation upon strong depolarizing inputs, mainly due to depolarization block.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
9/ Mapping ebGABAs' inputs with electrical or optogenetic stimulations, we found that these cells, unlike random GABA cells, receive little excitation by extra-hippocampal inputs. Instead, they are mostly recruited by intra-hippocampal ones.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
10/ What about inhibition? Do ebGABAs show distinct inhibitory wiring? Indeed, we show that compared to random GABA cells they receive weak local inhibition (with very little inputs from PV+ neurons). Instead, they are mostly inhibited by long-range inputs from the medial septum.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
11/ Finally, we imaged ebGABAs in vivo and found that these cells are among a minority of cells in the network that are activated by a variety of network states.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
12/ In summary, our study indicates that early-born hub cells could be a distributed feature of cortical circuits. In adulthood, these cells remain anatomically and functionally distinct from other GABA cells, speaking in favour of a predetermined program for their hub function.
Reply Retweet Označi sa "sviđa mi se"
Marco Bocchio 23. lis
Odgovor korisniku/ci @marco_bocchio
13/ Based on their unique wiring schemes, ebGABAs could exert a long-range hub function in adulthood, reading the activity of local cells and synchronizing them to other structures.
Reply Retweet Označi sa "sviđa mi se"