Biology subjects

Hökfelt, T.

Publications and source records attributed to Hökfelt, T..

3 recordsLinked to original sources

bioRxiv2022

Heterosynaptic Plasticity of the Visuo-auditory Projection Requires Cholecystokinin released from Entorhinal Cortex Afferents

The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex, using optogenetics of dual pathways. High-frequency laser stimulation (HFLS) of the visuo-auditory projection did not induce long-term potentiation (LTP). However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFLS of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that CCK expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the pre-synaptic input arrived 200 ms before post-synaptic firing, even after just five trials of pairing. Behaviorally, inhibition of CCK signaling blocked the generation of associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents.

neuroscience↗

bioRxiv2022

Genome-wide single cell annotation of the human protein-coding genes

An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new "tau" score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.

systems biology↗

bioRxiv2019

Developmental time course of SNAP-25 isoform regulation of hippocampal long-term synaptic plasticity and hippocampus-dependent learning

SNAP-25 is essential in activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During development and adulthood, SNAP-25 appears to have differential influences on long- and short-term synaptic plasticity in the hippocampus. The involvement of SNAP-25 in this process may be altered by two different splice variants expressed in adolescences versus adulthood in hippocampal neurons. This study suggests that the adolescent isoform, SNAP-25a can contribute to developmental regulation of the expression of LTD and LTP. In mice deficient in SNAP-25b, the adult isoform, Schaffer collateral-CA1 synapses showed slower release kinetics, reduced initial release probabilities, decreased LTP and enhanced LTD at 1 month. By 4 months of age, when mice have fully developed in the absence of SNAP-25b, the gene targeted mice appear to have compensated for the lack of the adult SNAP-25b isoform. Moreover, hippocampal-dependent training reversed reductions in LTP, but not LTD, seen at 1 month. In 4 month old adult mice, training prevented the compensatory reversal of LTD that had been observed prior to training. These findings support the hypothesis that immature SNAP-25a plays a strong role in the expression of plasticity at Schaffer collateral-CA1 synapses in adolescent mice, but compensatory mechanisms that reverse alterations in synaptic plasticity once mice reach adulthood.

neuroscience↗