Hsiang, M. | bioRxiv Science

bioRxiv2025

Hippocampal input-driven plasticity of prefrontal interneurons reveals a circuit basis for impaired spatial working memory.

Long-range projections from ventral hippocampus (vHPC) to medial prefrontal cortex (mPFC) support cognitive functions including spatial working memory (SWM). vHPC input targets multiple prefrontal interneuron classes, yet how hippocampal input recruits these populations in vivo, whether this recruitment is plastic, and how such plasticity influences cognition remain unknown. Here, we combined optical stimulation of mouse vHPC inputs with calcium recordings from discrete mPFC interneuron populations, revealing persistent activity-induced reweighting of hippocampal recruitment across prefrontal inhibitory microcircuits. Ex vivo electrophysiology and computational modeling implicated weakened monosynaptic hippocampal drive onto vasoactive intestinal polypeptide (VIP)-expressing interneurons in this circuit reconfiguration. Prior vHPC input stimulation and the schizophrenia-associated Df(16)A+/- mutation, which also yielded reduced hippocampal input onto VIP interneurons, produced convergent alterations in task-related VIP interneuron activity associated with poorer SWM task learning. These findings implicate hippocampal input to VIP interneurons as a key locus of plasticity capable of reconfiguring inhibitory microcircuit activity linked to impaired working memory task learning. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/665987v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@e26cb0org.highwire.dtl.DTLVardef@14d9d6borg.highwire.dtl.DTLVardef@9a0fc2org.highwire.dtl.DTLVardef@80afd1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2019

High genetic diversity of Plasmodium falciparum in the low transmission setting of the Kingdom of Eswatini

ABSTRACTO_ST_ABSBackgroundC_ST_ABSTo better understand transmission dynamics, we characterized Plasmodium falciparum (Pf) genetic diversity in Eswatini, where transmission is low and sustained by importation.\n\nMethods26 Pf microsatellites were genotyped in 66% of all confirmed cases from 2014-2016 (n=582). Population and within-host diversity were used to characterize differences between imported and locally-acquired infections, as determined by travel history. Logistic regression was used to assess the added value of diversity metrics to classify imported and local infections beyond epidemiology data alone.\n\nResultsThe parasite population in Eswatini was highly diverse (HE=0.75) and complex, with 67% polyclonal infections, a mean MOI of 2.2, and mean FWS of 0.84. Imported cases had comparable diversity to local cases, but exhibited higher MOI (2.4 versus 2.0; p=0.004) and lower mean FWS (0.82 vs. 0.85; p=0.03). Addition of MOI and FWS to multivariate analyses did not increase discrimination between imported and local infections.\n\nDiscussionIn contrast to the commonly held perception that Pf diversity declines with decreasing transmission intensity, isolates from Eswatini exhibited high parasite diversity consistent with high rates of malaria importation and limited local transmission. Estimates of malaria transmission intensity from genetic data need to consider the effect of importation, especially as countries near elimination.

genetics↗