Dear All,

I would like to cordially invite you to the Nencki Institute Seminar which will take place on the 7th of March at 3pm in the CN lecture Hall. We will host  dr. Grzegorz Wiera from the Wroclaw Medical University. His talk will be entitled: Input-specific GABAergic long-term plasticity at tetrapartite inhibitory synapses

Abstract:
Hebbian plasticity in excitatory synapses, taking the form of long-term potentiation (LTP) or depression
(LTD), has advanced our understanding of the molecular and cellular foundations underlying learning and
memory. Nevertheless, recent research has challenged the notion of limited plasticity in inhibitory
synapses and has revealed diverse forms of long-term GABAergic plasticity. However, the fundamental
mechanisms governing the induction, expression, and consolidation of inhibitory plasticity remain
enigmatic, primarily because of technical challenges arising from the diversity of interneurons (INs; e.g.,
containing somatostatin SST or parvalbumin PV). The induction mechanisms of known so far inhibitory
long-term plasticity (iLTP and iLTD) diverge significantly from those in excitatory synapses. A key
feature of GABAergic plasticity is its heterosynaptic induction mechanism, in which unstimulated
inhibitory synapses change in response to the activity of nearby excitatory synapses. In brain slices, iLTP
induction typically requires brief administration of NMDA for a short period (3 min), whereas iLTD
induction requires an extended treatment duration.
In this context, we aim to elucidate the synapse-specificity and detailed molecular mechanisms of
GABAergic plasticity together with its role in learning. To this end, we used patch clamp recordings in
brain slices, optogenetics, single-molecule tracking, immunofluorescence, and behavioral studies. Our
experiments revealed heterosynaptic crosstalk between excitatory and inhibitory plasticity. The induction
of excitatory LTD concurrently led to the expression of different forms of heterosynaptic GABAergic
plasticity at different inhibitory synapses. In contrast, the excitatory LTP was simultaneously co-expressed
with iLTP at all analyzed synapses. To reveal the role of the extracellular matrix in GABAergic plasticity,
we used chondroitinase or hyaluronidase treatment. Our results show that the manipulation of distinct
components of the extracellular matrix selectively affects GABAergic plasticity in specific projections.
Brain chondroitin digestion specifically impaired iLTP in synapses between SST INs and CA1 pyramidal
cells (PCs), whereas hyaluronan digestion hindered PV→PC iLTP induction. Additionally, we explored
the role of different integrins and matrix metalloproteinases in the crosstalk between plastic changes at
excitatory and inhibitory synapses. Finally, we demonstrate the critical dependence of iLTP maintenance
on the transsynaptic interactions between neuroligin-2 and neurexin. Peptide blocking this adhesion
abolished already induced GABAergic plasticity. In summary, these findings reveal the intricate
plasticitome of CA1 PCs and underscore the crucial roles of extracellular matrix, integrins, and
neuroligin-2 in the molecular mechanisms of local crosstalk between excitatory and inhibitory synapses
and their plasticities.