Biology subjects

Trachtenberg, J.

Publications and source records attributed to Trachtenberg, J..

3 recordsLinked to original sources

bioRxiv2025

Comparative transcriptomics reveals shifts in cortical architecture at themetatherian/eutherian transition

The neocortex, a layered structure unique to mammals, supports higher-order functions including perception, learning, and decision-making. While its laminar architecture is broadly conserved, the cell type-specific organization of the cortical column has not been compared across species that diverged early in mammalian evolution. To address this, we used single-nucleus RNA sequencing and spatial transcriptomics to compare gene expression, cell types, and laminar architecture in the primary visual cortex (V1) of metatherian (Monodelphis domestica) and eutherian (Mus musculus) mammals. We show that spatio-transcriptomic distinctions between supragranular (layer 2/3) and infragranular (layer 5) intratelencephalic (IT) neurons are more pronounced in mice, consistent with lineage-specific specialization. Mouse cortex also exhibits a lower relative density of parvalbumin-positive (PV) GABAergic neurons and redistributed perineuronal nets, consistent with altered constraints on plasticity. Together, these findings demonstrate substantial variation in the cellular and spatial organization of the cortical column across deeply diverged mammals, challenging the view that local cortical architecture is uniformly conserved. Significance StatementThe neocortex supports perception and flexible behavior in mammals, yet how its cellular composition varies across early mammalian divergences has not been directly examined. By comparing transcriptomic cell types and their spatial organization in the primary visual cortex of a metatherian (opossum) and a eutherian (mouse), we show that major classes and laminar structure are broadly conserved, but intratelencephalic neurons differ substantially. These differences are accompanied by shifts in inhibitory circuitry and extracellular scaffolding, indicating divergent modes of cortical organization and plasticity across mammalian lineages. Our findings challenge the assumption that neocortical columns are uniformly conserved and identify specific cellular populations that vary across deeply diverged therian mammals.

neuroscience↗

bioRxiv2025

Establishing a continuum of cell types in the visual cortex

The mammalian cerebral cortex is composed of neurons whose properties vary in a continuous fashion rather than falling into discrete cell types. In the mouse visual cortex, excitatory neurons in layer 2 and 3 (L2/3) form such a continuum along cortical depth, patterned by the graded expression of hundreds of genes. Here we sought to understand how this continuum develops and contributes to cortical wiring. Using single-nucleus multiomics (RNA- and ATAC-Seq) and spatial transcriptomics, we show that the L2/3 continuum is established in two phases. During the first postnatal week, a genetically hardwired program establishes a primitive continuum of cell identities spanning the depth of L2/3. The second program, promoted by visual experience, is later superimposed upon the preexisting continuum. This second phase is driven by activity-regulated transcription factors that drive the L2/3 depth-dependent expression of genes linked to synaptic function and plasticity. We show that neurons at different positions along the L2/3 continuum project preferentially to distinct higher visual areas and that visual deprivation disrupts targeting to some higher visual areas while sparing others. Thus, cortical continua emerge through a stepwise process in which genetic programs and sensory experience specify neuronal identity and sculpt intracortical wiring specificity.

neuroscience↗

bioRxiv2022

The development of receptive field tuning properties in mouse binocular primary visual cortex

The mouse primary visual cortex is a model system for understanding the relationship between cortical structure, function, and behavior (Seabrook et al., 2017; Chaplin and Margrie, 2020; Hooks and Chen, 2020; Saleem, 2020; Flossmann and Rochefort, 2021). Binocular neurons in V1 are the cellular basis of binocular vision, which is required for predation (Scholl et al., 2013; Hoy et al., 2016; La Chioma et al., 2020; Berson, 2021; Johnson et al., 2021). The normal development of binocular responses, however, has not been systematically measured. Here, we measure tuning properties of neurons to either eye in awake mice of either sex from eye-opening to the closure of the critical period. At eye-opening, we find an adult-like fraction of neurons responding to the contralateral-eye stimulation, which are selective for orientation and spatial frequency; few neurons respond to ipsilateral eye and their tuning is immature. Fraction of ipsilateral-eye responses increases rapidly in the first few days after eye opening and more slowly thereafter, reaching adult levels by critical period closure. Tuning of these responses improves with a similar time course. The development and tuning of binocular responses parallels that of ipsilateral-eye responses. Four days after eye-opening, monocular neurons respond to a full range of orientations but become more biased to cardinal orientations. Binocular responses, by contrast, lose their cardinal bias with age. Together, these data provide an in-depth accounting of the development of monocular and binocular responses in the binocular region of mouse V1 using a consistent set of visual stimuli and measurements. Significance statementIn this manuscript, we present a full accounting of the emergence and refinement of monocular and binocular receptive field tuning properties of thousands of pyramidal neurons in mouse primary visual cortex. Our data reveal new features of monocular and binocular development that revise current models on the emergence of cortical binocularity. Given the recent interest in visually guided behaviors in mice that require binocular vision, e.g. predation, our measures will provide the basis for studies on the emergence of the neural circuitry guiding these behaviors.

neuroscience↗