Biology subjects

Bulovaite, E.

Publications and source records attributed to Bulovaite, E..

7 recordsLinked to original sources

bioRxiv2026

Discovery of the Honeycomb Synapse in Spinal Motor Circuits

The structural and molecular diversity of synapses in the nervous system contributes to the specialisation of neural circuits underlying diverse behaviours. We have discovered a morphologically distinct postsynaptic specialisation in the mammalian spinal cord. We have named this the Honeycomb Synapse based on its elaborate postsynaptic nanostructure, comprising rings formed of ~6 scaffolding protein domains that create multiple perforations throughout the large postsynaptic domain. Analysis of the organisation of other synaptic proteins reveals that Honeycomb Synapses harbour mixed signalling properties structurally facilitated by a postsynaptic scaffold matrix supporting chemical transmission, with gap junction proteins occupying some of the perforations. We reveal anatomical diversity in the presence of Honeycomb Synapses on populations of -motoneurons across the lumbar spinal cord in mice from approximately 2 weeks of age through to adulthood. The Honeycomb Synapse was found to be a subtype of synapse within the Ia afferent monosynaptic stretch reflex circuit. Finally, we have identified that Honeycomb Synapses are highly vulnerable to degeneration in two different genetically engineered mouse models of Amyotrophic Lateral Sclerosis (ALS), contributing to monosynaptic stretch reflex circuit dysfunction. These findings suggest that synaptic diversity within circuits may confer selective vulnerability to distinct synaptic subclasses.

neuroscience↗

bioRxiv2026

A Brainwide Atlas of Synaptic Nanoarchitecture Across the Mouse Lifespan

How biological complexity emerges from the ordered assembly of molecular building blocks into supramolecular systems remains a central question, particularly in the mammalian brain with its vast synaptic diversity. We introduce NanoSYNMAP, a genetic, optical, and computational platform that integrates FRET with synaptome mapping to quantify nanoscale proximity of proteins in individual synapses brain-wide. We generate the first brain atlas of synaptic nanoarchitecture, based on the proximity of postsynaptic MAGUK supercomplexes. This reveals a molecular logic in which spacing of supramolecular assemblies specifies nanoscale architecture that organizes the global synaptome architecture. Nanoarchitecture varies across brain regions, differentiates during postnatal development, and remodels with aging. Supercomplex proximity reflects scaffold abundance, nanodomain organization, and competitive interactions among MAGUK assemblies. Deletion of a neuropsychiatric risk gene triggers widespread reorganization of nanoscale architecture. These findings establish molecular proximity as a fundamental scalable dimension of synapse diversity in health and disease.

neuroscience↗

bioRxiv2024

3D super-resolution imaging of PSD95 reveals an abundance of diffuse protein supercomplexes in the mouse brain

PSD95 is an abundant scaffolding protein that assembles multiprotein complexes controlling synaptic physiology and behavior. Confocal microscopy has previously shown that PSD95 is enriched in the postsynaptic terminals of excitatory synapses and 2D super-resolution microscopy further revealed that it forms nanoclusters. In this study, we utilized 3D super-resolution microscopy to examine the nanoarchitecture of PSD95 in the mouse brain, characterizing over 8 million molecules. While we were able to identify structural subtypes previously reported, imaging in 3D allowed us to classify these with higher accuracy. Furthermore, 3D super-resolution microscopy enabled the quantification of protein levels, revealing an abundance of PSD95 molecules existed outside of synapses as a diffuse population of supercomplexes, containing multiple copies of PSD95. Further analysis of the supercomplexes containing two units identified two populations: one that had PSD95 molecules separated by 39 {+/-} 2 nm, and a second with a separation of 94 {+/-} 27 nm. These results suggest that PSD95 supercomplexes containing multiple protein copies assemble outside the synapse and then integrate into the synapse to form a supramolecular nanocluster architecture.

biophysics↗

bioRxiv2023

Sleep maintains excitatory synapse diversity in the cortex and hippocampus

How sleep deprivation affects cognition remains elusive. Synaptome mapping of excitatory synapses in 125 regions of the mouse brain revealed that sleep deprivation selectively reduces synapse diversity in the cortex and hippocampus. Sleep deprivation targeted specific types and subtypes of excitatory synapses while maintaining total synapse density. Altered synaptic responses to neural oscillations in a computational model suggest that sleep prevents cognitive impairments by maintaining normal brain synaptome architecture.

neuroscience↗

bioRxiv2023

The organisation and turnover of synaptic proteins within molecular supercomplexes.

The concept that dimeric protein complexes in synapses can sequentially replace their subunits has been a cornerstone of Francis Cricks 1984 hypothesis, explaining how long-term memories could be maintained in the face of short protein lifetimes. However, it is unknown whether the subunits of protein complexes that mediate memory are sequentially replaced in the brain and if this process is linked to protein lifetime. We address these issues by focusing on supercomplexes assembled by the abundant postsynaptic scaffolding protein PSD95, which plays a crucial role in memory. We used single-molecule detection, super-resolution microscopy and MINFLUX to probe the molecular composition of PSD95 supercomplexes in mice carrying genetically encoded HaloTags, eGFP and mEos2. We found a population of PSD95-containing supercomplexes comprised of two copies of PSD95, with a dominant 12.7 nm separation. Time-stamping of PSD95 subunits in vivo revealed that each PSD95 subunit was sequentially replaced over days and weeks. Comparison of brain regions showed subunit replacement was slowest in the cortex, where PSD95 protein lifetime is longest. Our findings reveal that protein supercomplexes within the postsynaptic density can be maintained by gradual replacement of individual subunits providing a mechanism for stable maintenance of their organization. Moreover, we extend Cricks model by suggesting that synapses with slow subunit replacement of protein supercomplexes and long protein lifetimes are specialized for long-term memory storage and that these synapses are highly enriched in superficial layers of the cortex where long-term memories are stored.

neuroscience↗

bioRxiv2021

Developmental resilience of synaptome architecture

Neurodevelopmental disorders of genetic origin delay the acquisition of normal abilities and cause disabling phenotypes. Spontaneous attenuation and even complete amelioration of symptoms in early childhood and adolescence occur in many disorders1-10, suggesting that brain circuits possess an intrinsic capacity to repair themselves. We examined the molecular composition of almost a trillion excitatory synapses on a brain-wide scale between birth and adulthood in mice carrying a mutation in the homeobox transcription factor Pax6, a neurodevelopmental disorder model11. Pax6 haploinsufficiency had no impact on total synapse number at any age. By contrast, the postnatal expansion of synapse diversity and acquisition of normal synaptome architecture were delayed in all brain regions, interfering with network and cognitive functions. Specific excitatory synapse types and subtypes were affected in two key developmental age-windows. These phenotypes were reversed within 2-3 weeks of onset, restoring synaptome architecture to its normal developmental trajectory. Synapse subtypes with high rates of protein turnover mediated these events. These results show synaptome remodelling confers resilience to neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

A brain atlas of synapse protein lifetime across the mouse lifespan.

Protein turnover is required for synapse maintenance and remodelling and may impact memory duration. We quantified the lifetime of postsynaptic protein PSD95 in individual excitatory synapses across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of protein lifetimes that may extend from a few hours to several months, with distinct spatial distributions in dendrites, neuron types and brain regions. Short protein lifetime (SPL) synapses are enriched in developing animals and in regions controlling innate behaviors, whereas long protein lifetime (LPL) synapses accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. The protein lifetime synaptome architecture is disrupted in an autism model, with synapse protein lifetime increased throughout the brain. These findings add a further layer to synapse diversity in the brain and enrich prevailing concepts in behavior, development, ageing and brain repair.

neuroscience↗