|
@marco_bocchio | |||||
|
1/ #tweeprint time! If you are interested in #interneurons, #hippocampus and developmental mechanisms of neural circuit function, check out our new preprint “Hippocampal hub neurons maintain unique functional properties throughout their lifetime” biorxiv.org/content/10.110…
|
||||||
|
||||||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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’.
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
3/ A few years later, @PicardoMichel and others in the lab (in collaboration with @GordFishell lab) found that many hub cells were GABA cells born early in embryogenesis (thus termed ‘early-born GABA cells’ or ‘ebGABAs’).
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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?
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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.
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/hKFPVXlBlL
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/o3NxuTVkV8
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/UuA0BOfMIw
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/tHQ5koDJW7
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/gqG0JAqw8c
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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. pic.twitter.com/VSaYwbggKB
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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.
|
||
|
|
||
|
Marco Bocchio
@marco_bocchio
|
23. lis |
|
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.
|
||
|
|
||