Biology subjects

Roy, D. S.

Publications and source records attributed to Roy, D. S..

3 recordsLinked to original sources

bioRxiv2024

Serotonin Promotes Vesicular Association and Fusion by Modifying Lipid Bilayers

The primary event in chemical neurotransmission involves the fusion of a membrane-limited vesicle at the plasma membrane and the subsequent release of its chemical neurotransmitter cargo. The cargo itself is not known to have any effect on the fusion event. However, amphiphilic monoamine neurotransmitters (e.g. serotonin and dopamine) are known to strongly interact with lipid bilayers and to affect their mechanical properties, which can in principle impact membrane-mediated processes. Here we probe whether serotonin can enhance the association and fusion of artificial lipid vesicles in vitro. We employ Fluorescence Correlation Spectroscopy and Total Internal Reflection Fluorescence microscopy to measure the attachment and fusion of vesicles whose lipid compositions mimic the major lipid components of synaptic vesicles. We find that association between vesicles and supported lipid bilayers are strongly enhanced in a serotonin dose-dependent manner, and this drives an increase in the rate of spontaneous fusion. Molecular dynamics simulations and fluorescence spectroscopy data show that serotonin insertion increases the water content of the hydrophobic part of the bilayer. This suggests that the enhanced membrane association is likely driven by an energetically favourable drying transition. Other monoamines such as dopamine and norepinephrine, but not other related species such as tryptophan, show similar effects on membrane association. Our results reveal a lipid bilayer-mediated mechanism by which monoamines can themselves modulate vesicle fusion, potentially adding to the control toolbox for the tightly regulated process of neurotransmission in vivo. TOC graphics O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=68 SRC="FIGDIR/small/576155v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@2717c5org.highwire.dtl.DTLVardef@899c21org.highwire.dtl.DTLVardef@697232org.highwire.dtl.DTLVardef@c850a0_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Dynamic and selective engrams emerge with memory consolidation

Episodic memories are encoded by sparse populations of neurons activated during an experience.1 These neural ensembles constitute memory engrams that are both necessary and sufficient for inducing recall even long after memory acquisition.2 This suggests that following encoding, engrams are stabilized to reliably support memory retrieval. However, little is known about the temporal evolution of engrams over the course of memory consolidation or how it impacts mnemonic properties. Here we employed computational and experimental approaches to examine how the composition and selectivity of engrams change with memory consolidation. We modeled engram cells using a spiking recurrent neural network that yielded three testable predictions: memories transition from unselective to selective as neurons are removed from and added to the engram, inhibitory activity during recall is essential for memory selectivity, and inhibitory synaptic plasticity during memory consolidation is critical for engrams to become selective. Using the Cal-Light system to tag activated neurons in vivo with high spatiotemporal precision3 as well as optogenetic and chemogenetic techniques, we conducted contextual fear conditioning experiments that supported each of our models predictions. Our results reveal that engrams are dynamic even within hours of memory consolidation and that changes in engram composition mediated by inhibitory synaptic plasticity are crucial for the emergence of memory selectivity. These findings challenge classical theories of stable memory traces and point to a close link between engram state and memory expression.

neuroscience↗

bioRxiv2019

Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

GRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC=\"FIGDIR/small/668483v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (34K):\norg.highwire.dtl.DTLVardef@1957e90org.highwire.dtl.DTLVardef@1a83d79org.highwire.dtl.DTLVardef@5bd5d5org.highwire.dtl.DTLVardef@133c879_HPS_FORMAT_FIGEXP M_FIG C_FIG SUMMARYNeuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, and cortex. It has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected. Here, we report the hitherto most extensive engram map for contextual fear memory by characterizing activity-tagged neurons in 409 regions using SHIELD-based tissue phenotyping. The mapping was aided by a novel engram index, which identified cFos+ brain regions holding engrams with a high probability. Optogenetic manipulations confirmed previously known engrams and revealed new engrams. Many of these engram holding-regions were functionally connected to the CA1 or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engrams, which mimics natural memory recall, conferred a greater level of memory recall than reactivation of a single engram ensemble. Overall, our study supports the hypothesis that a memory is stored in functionally connected engrams distributed across multiple brain regions.

neuroscience↗