Biology subjects

Vatne, G. H.

Publications and source records attributed to Vatne, G. H..

5 recordsLinked to original sources

bioRxiv2026

Large-scale volumetric two-photon calcium imaging enables cellular-resolution mesoscopic mapping of marmoset cortical areas

Primate neocortex is organized into functionally defined domains. Understanding how the functional organization within each domain emerges from single-cell tuning properties has been hampered by the lack of imaging tools that can capture large-scale activity at different depths of the scattering primate brain at cellular resolution and physiological timescales. Here, we demonstrate mesoscopic and volumetric cellular-resolution calcium imaging of entire cortical areas in the marmoset brain at multi-Hertz rates by combining fluorescence lifetime-limited temporally multiplexed two-photon recording based on Light Beads Microscopy (LBM) with optimized calcium indicator targeting. Using this approach, we perform volumetric recording of neuronal population activity within cortical volumes spanning up to 4 x 4 x 0.3 mm3 capturing the simultaneous activity of over 96,000 cells, including more than 46,000 stimulus-responsive neurons. In auditory cortex, we found fine-grain heterogeneous tuning of individual neurons to frequencies within broader tonotopic gradients. In the middle temporal area (MT) we found direction tuning along functional continua rather than discrete categories, encompassing uni-, bi-, and pandirectional tuning, where cells with similar tuning tend to cluster. Tuning direction follows a columnar organization with a lateral periodicity of [~]500 {micro}m and low variability across depth. Columns are organized by a pinwheel structure. Noise correlations between cells, revealing functional interactions, decay isotropically and monotonically with distance but remain significant even at lateral distances exceeding 3 mm and thus the scale of multiple columns. Together, these discoveries reveal the need for neurotechnologies bridging scales from single cells to multi-columnar systems. The technological advancements open the door for future large-scale, cellular-resolution investigations of functional organization and population dynamics across entire cortical areas in the primate brain.

neuroscience↗

bioRxiv2026

Perineuronal nets reflect a continuum of fast-spiking specialization in adult parvalbumin interneurons

Perineuronal nets (PNNs) preferentially enwrap parvalbumin (PV) interneurons, regulating plas-ticity and circuit function. The molecular differences between PNN-positive and PNN-negative PV neurons remain unknown. We combined Xenium spatial transcriptomics with PNN-labeling in adult mouse cortex (378,349 cells) and found that 97% of PNNs enwrap PV neurons; sub-stantially higher than previous estimates. PNN status reflected a transcriptional continuum rather than discrete subtypes. A classifier trained on Xenium data (AUC = 0.87) applied to Allen Brain scRNA-seq data, enabled genome-wide analysis of 34,326 cortical PV neurons. PNN-positive PV neurons expressed mature fast-spiking markers: Kv3 channels, mature NMDA subunits (Grin2a), fast-kinetic GABA-A receptors (Gabra1), oxidative phosphorylation genes, and gap junctions (Gjd2). PNN-negative PV neurons expressed neuropeptides and GABA-A subunits typical of Sst interneurons, suggesting a transcriptomic boundary between cell types and potentially ele-vated plasticity. This establishes PNN status as a molecular correlate of PV cell specialization, with implications for therapeutic strategies targeting cortical plasticity.

neuroscience↗

bioRxiv2024

Deciphering the Role of Aggrecan in Parvalbumin Interneurons: Unexpected Outcomes from a Conditional ACAN Knockout That Eliminates WFA+ Perineuronal Nets

The transition from juvenile to adult is accompanied by the maturation of inhibitory parvalbumin-positive (PV+) neurons and reduced plasticity. This transition involves the formation of perineuronal nets (PNNs), a dense configuration of the extracellular matrix that predominantly envelops parvalbumin-positive (PV+) neurons. Aggrecan, a proteoglycan encoded by the ACAN gene, has been shown to have a key role in the PNNs as knock-out of ACAN in the adult brain reactivates juvenile plasticity, but the contribution of different cell populations is unknown Here, we establish and characterize a mouse model in which ACAN is selectively knocked out (KO) in PV+ neurons (ACANflx/PVcre). Moreover, we develop a viral tool to perform similar cell-type directed KO in adult mice. Both models are compared with the traditional method of PNN removal, namely enzymatic degradation of PNNs with Chondroitinase ABC (chABC). We show that PV+ neurons in adult ACANflx/PVcre mice do not produce PNNs that are labeled by Wisteria floribunda agglutinin (WFA), the most commonly used PNN marker. Surprisingly, electrophysiological properties of PV+ interneurons in the visual cortex (V1) and ocular dominance plasticity of adult ACANflx/PVcre mice were similar to controls. In contrast, AAV-mediated ACAN knockout in adult mice increased ocular dominance plasticity. Moreover, in vivo chABC treatment of KO mice resulted in reduced firing rate of PV+ cells and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC), a phenotype associated with chABC treatment of WT animals. This suggests compensatory mechanisms in the germline KO. Indeed, qPCR of bulk tissue indicates that other PNN components are expressed at higher levels in the KO animals. Finally, we perform memory-and behavioral testing to see if the lack of ACAN from PV+ neurons throughout development affected stereotypic behaviors and memory processing. ACANflx/PVcre mice have learning and memory abilities similar to controls, but use bold search strategies during navigation in the Morris water maze. The low level of anxiety-related behavior is confirmed in an open field and zero maze, where they spent nearly twice the time in open areas.

neuroscience↗

bioRxiv2021

An updated suite of viral vectors for in vivo calcium imaging using local and retro-orbital injections

Calcium imaging using genetically encoded Ca2+ indicators (GECIs) is a widely adopted method to measure neural activity in modern neuroscience. Here, we explore the use of systemically administered viral vectors for brain-wide expression of GECIs, and adapt novel GECIs to optimize signal-to-noise. We show that systemic injections of PHP.eB AAVs to express GECIs is a highly promising technique for imaging neural activity and circumvent the need for transgenic GECI expressing mouse lines. We also establish the use of soma-targeted GECIs that outperform current Ca2+ indicators using both systemic and local virus injections.

neuroscience↗

bioRxiv2019

Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail

Schwann cells myelinate selected axons in the peripheral nervous system (PNS) and contribute to fast saltatory conduction via the formation of compact myelin, in which water is excluded from between tightly adhered lipid bilayers. Peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS), are incurable demyelinating conditions that result in pain, decrease in muscle mass, and functional impairment. Many Schwann cell proteins, which are directly involved in the stability of compact myelin or its development, are subject to mutations linked to these neuropathies. The most abundant PNS myelin protein is protein zero (P0); point mutations in this transmembrane protein cause CMT subtype 1B and DSS. P0 tethers apposing lipid bilayers together through its extracellular immunoglobulin-like domain. Additionally, P0 contains a cytoplasmic tail (P0ct), which is membrane-associated and contributes to the physical properties of the lipid membrane. Six CMT- and DSS-associated missense mutations have been reported in P0ct. We generated recombinant disease mutant variants of P0ct and characterized them using biophysical methods. Compared to wild-type P0ct, some mutants have negligible differences in function and folding, while others highlight functionally important amino acids within P0ct. For example, the D224Y variant of P0ct induced tight membrane multilayer stacking. Our results show a putative molecular basis for the hypermyelinating phenotype observed in patients with this particular mutation and provide overall information on the effects of disease-linked mutations in a flexible, membrane-binding protein segment.

biophysics↗