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Bushnell, H.

Publications and source records attributed to Bushnell, H..

3 recordsLinked to original sources

Cell-type specific inhibitory dynamics shape binocular response normalization in visual cortex

Response normalization during sensory processing is a canonical cortical computation thought to emerge from inhibition-stabilized networks (ISNs). A key prediction from ISNs is that inhibition tracks and scales with excitation, leading to sublinear response summation, but which interneuron classes mediate this operation is unclear. Here, we investigate temporal dynamics and response summation in parvalbumin (PV) and somatostatin (SST) interneurons in mouse binocular visual cortex (bV1). We find that both PV and SST interneurons are binocular but exhibit distinct temporal dynamics and summation profiles. Binocular responses in PV interneurons tracked pyramidal neuron responses, exhibiting sublinear summation consistent with ISN models. In contrast, binocular responses SST interneurons exhibited rapid temporal dynamics and linear or supralinear summation, deviating from ISN predictions. While both PV and SST neurons received excitatory drive via interhemispheric callosal input, they exhibited distinct cellular properties, synaptic dynamics and input-output transformations. Biophysically constrained simulations indicated that cellular and synaptic differences alone were insufficient to reproduce the observed response dynamics in vivo during binocular integration, which were better explained by class-specific differences in local inhibitory circuit motifs. Together, our results indicate that heterogeneous, cell-type-specific inhibitory dynamics shape response normalization in bV1, with PV but not SST interneurons having ISN-like properties.

neuroscience↗

Distinct neurogenic progenitor cell populations balance cell type production in the embryonic mouse retina

Mammalian vision depends on the reliable production of over 100 neural cell types from multipotent retinal progenitor cells. How so many cell types are generated in the correct proportions throughout the retina remains incompletely understood. Focusing on the early embryonic period in mice, we found that retinal neurogenesis is organized through discrete neurogenic progenitor cell (NPC) populations with distinct fate biases. NPCs expressing Galanin primarily produce retinal ganglion cells and amacrine cells, whereas Olig2-expressing NPCs produce cones and horizontal cells in the same temporal window. Clonal analysis revealed that these two fate-biased NPC populations arise predominantly from asymmetric, renewing progenitor cell divisions that produce one fate-biased NPC daughter cell. Differential Notch signaling regulates the production of these NPC populations, with Galanin+ and Olig2+ NPCs representing NotchHigh and NotchLow states, respectively. Manipulating Notch signaling was sufficient to toggle their production. The expression of Notch signaling components across NPCs is consistent with a lateral inhibition mechanism, in which fate-biased NPCs promote neighboring cells to adopt a complementary fate-biased NPC state. These findings suggest that the robust production of diverse retinal cell types is achieved through local feedback that balances discrete, fate-biased NPC populations.

developmental biology↗

Role of Epigenetics in Unicellular to Multicellular Transition in Dictyostelium

The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that exists in both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity. While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and syntenic analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity. These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate the evolution of multicellularity. One Sentence SummaryEpigenetic regulation of multicellularity

genetics↗