XXXX targets astrocytes to attenuate synaptic plasticity via modulation of the @entity40155 / @entity8115 signalling.

@entity8115 @entity308 @entity7242 @entity34749 @entity5829 @entity1399 @entity71 @entity9956 @entity2414 @entity40155 @entity9
UNASSIGNED: Long-term potentiation (LTP), a major cellular correlate of memory storage, depends on activation of the ERK/MAPK signalling pathway, but the cell type-specific localization of activated MAPKs remains unknown. We found that in the @entity1399 field of the hippocampus, shortly after LTP induction, an increase in the number of MAPK-positive cells occurred specifically among astrocytes of the stratum radiatum, suggesting a putative role of astrocytes for LTP. @entity5829 ( @entity9956 ) is an antidepressant which is used to treat major @entity308 , but also other pathologies such as @entity9 or @entity71 . Tricyclic antidepressants such as @entity9956 may cause @entity2414 as a side effect. However, biological underpinnings of this effect still remain unclear. Here, we show that @entity9956 inhibited the astrocytic MAPK activation and thereby hindered synaptic potentiation. These effects correlated with a reduced neuronal activation in the stratum pyramidale, thereby prompting us to analyse a regulator of LTP located at the astrocyte-neuron interface in the stratum radiatum, namely the @entity40155 / @entity8115 signalling pathway. @entity9956 enhanced @entity8115 clustering, which favoured an increased @entity40155 -mediated @entity8115 phosphorylation and elevated @entity8115 forward signalling. The co-administration of @entity9956 with the @entity7242 inhibitor @entity34749 , which blocks @entity8115 forward signalling, could partially reverse the LTP attenuation, further supporting the targeting of the @entity40155 / @entity8115 pathway by @entity9956 . Thus, our findings suggest a putative novel mechanism for @entity9956 to modulate LTP through the regulation of the @entity40155 / @entity8115 signalling pathway. A further exploration of the molecular and behavioral consequences of targeting @entity40155 / @entity8115 might help to improve the clinical use of @entity9956 .
