Biology subjects

Lukacsovich, D.

Publications and source records attributed to Lukacsovich, D..

5 recordsLinked to original sources

bioRxiv2026

Multimodal profiling and intersectional genetics reveal CA1 border inhibitory neuron diversity and postnatal emergence of retrosplenial connectivity

Inhibitory neurons (INs) at the stratum radiatum/stratum lacunosum-moleculare border of hippocampal CA1 comprise diverse populations, including long-range-projecting neurons that innervate the retrosplenial cortex (RSCtx). However, their molecular organization and developmental connectivity remain poorly understood. Here, we combine multimodal transcriptomic profiling, intersectional genetics, and retrograde tracing to characterize CA1 border INs. We identified two major caudal ganglionic eminence-derived, Cxcl14-enriched populations distinguished by Syt6/Cck-related and Ntng1-expressing transcriptional profiles. We then generated a Cxcl14-Cre mouse line that, when combined with an IN-specific viral enhancer, provides genetic access to CA1 border INs. Retrograde labeling established that CA1 INs projecting to the RSCtx belong to the Ntng1-expressing population, and that this long-range projection emerges during postnatal mouse development, between postnatal days 3 and 5. Finally, analysis of genes encoding cell-surface proteins, key regulators of connectivity, revealed distinct expression profiles in RSCtx-projecting and SYT6-positive INs. Together, these findings establish a molecular and developmental framework for CA1 border IN diversity and provide a genetic strategy for investigating the assembly and function of these inhibitory circuits.

neuroscience↗

bioRxiv2025

Endothelial Adgrl2 expression and alternative splicing controls the cerebrovasculature

Central nervous system development requires parallel but interrelated processes of neural circuit assembly and vascularization. Intersecting between these two processes, the cell-adhesion G-protein coupled receptor Adgrl2 is expressed in select neuron populations where it has been found to localize and control the assembly of specific synaptic sites. Further, Adgrl2 is found to be expressed in select non-neuronal brain cells, where it is restricted to endothelial cells. Testing for Adgrl2 function in these cells, here we find that endothelial cell specific Adgrl2 deletion results in an impairment in cerebrovascular integrity. To understand how it might be possible for Adgrl2 to function independently in neuronal and endothelial contexts, we analyzed single-cell RNA sequencing datasets for differences in transcriptional identity between these cell classes. Doing so, we find that expression of Adgrl2 mRNA is subject to robust cell type-specific alternative splicing, resulting in distinct isoforms being produced in neurons compared to endothelial cells. Investigating the functional implication of this cell type-specific alternative splicing, we find that forced expression of the neuronal isoform of Adgrl2 in endothelial cells leads to alterations in cerebrovascular properties. Morphologically, endothelial cells with the non-native neuronal Adgrl2 isoform induce the formation of ectopic glutamatergic synaptic contacts onto endothelial cells, indicating alterations in the cell-cell recognition process. Functionally, in direct contrast to endothelial Adgrl2 deletion, this genetic expression switch instead enhances blood-brain barrier integrity. This overly restrictive cerebrovascular function results in dysregulation of blood to cerebrospinal fluid homeostasis, enlargement of brain ventricles, and a higher risk of hydrocephalus. As such, alternative splicing serves as a cell type specific mechanism that provides isoform specific Adgrl2 for discerning functions controlling neural circuit assembly and cerebrovascular homeostasis.

neuroscience↗

bioRxiv2021

Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum

Ventral subiculum (vSUB) is integral to the regulation of stress and reward, however the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular spiking (RS) and burst spiking (BS) principal neurons. Surprisingly, we found that intrinsic connectivity and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that vSUB PVs make preferential contact with RS neurons in males, but BS neurons in females. Furthermore, we determined that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 maintains synapse density at PV-RS synapses in males, but suppresses presynaptic release at the same synapses in females. HighlightsO_LIOverall inhibitory strength in ventral subiculum is cell-type specific C_LIO_LIPV circuits in ventral subiculum are organized sex-specifically C_LIO_LINrxn3 function in PV interneurons depends on postsynaptic cell identity C_LIO_LINrxn3 has distinct functions at PV-RS synapses in females compared to males C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/440943v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@7fcf99org.highwire.dtl.DTLVardef@1167f82org.highwire.dtl.DTLVardef@d5c79org.highwire.dtl.DTLVardef@1320f09_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

neuroscience↗

bioRxiv2020

Transcriptomic homogeneity and an age-dependent onset of hemoglobin expression characterize morphological PV types

The diversity created by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. For example, parvalbumin interneurons (PV-INs) comprise of a main transcriptomic cluster within all inhibitory cells. However, transcriptomics alone has not resolved the different morphological PV types that exist. To close this gap, we used single-cell RNA-seq in morphologically identified PV-INs, sampled from 10 days to 3 months-old mice and studied their transcriptomic states in the morphological, physiological, and developmental domains. Our findings reveal novel genes whose expression separately identify morphological types but corroborate an overall transcriptomic homogeneity among PV-INs. Surprisingly, morphological PV types display uniform cell adhesion molecule (CAM) profiles, suggesting that CAMs do not actively maintain their specificity of wiring after development. Finally, our results reveal a pronounced change of transcriptomic states between postnatal days 20 and 25, during which PV-INs display a rapid and unexpected onset of hemoglobin gene expression which remains stable in later development.

neuroscience↗

bioRxiv2019

Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. The general excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor event in the cells whole transcriptome, can underlie distinct cell-type identity.

neuroscience↗