Biology subjects

Thong, S.

Publications and source records attributed to Thong, S..

4 recordsLinked to original sources

bioRxiv2026

Investigating cross-memory interactions of timing structures

Motor and episodic memories are classically conceptualised as distinct memory domains. However, both memory sequences are characterised by order and timing of their elements. Generalisation has been previously documented between these different memories, with a shared ordinal structure facilitating learning. However, it is unclear whether this generalisation also applies to the timing structure of a sequence. In a between-subject design, healthy adults (N = 143) learned and reproduced motor and episodic memory sequences with either the same or different timing structures. Contrary to expectations, recall of an episodic timeline was poorer when preceded by learning a motor sequence with the same timing structure. Motor sequence reproduction was not affected by prior episodic encoding. The findings do not support the hypothesis of cross-domain generalisation of timing structure between episodic and motor memories. However, the observed interference may suggest some overlap in the mechanism encoding timing information between memory systems.

neuroscience↗

bioRxiv2025

Generalisation between motor and declarative memory sequences: A conceptual replication of Mosha & Robertson (2016)

Motor and declarative memory systems have been traditionally considered distinct. However, a study by Mosha and Robertson (2016) reported striking evidence of generalisation between motor and declarative learning. Specifically, learning improved if the current task (e.g. motor sequence) shared the same high-level ordinal structure as an earlier task (e.g. word list), demonstrating cross-domain transfer of unstable memories. This finding has significant implications for our understanding and conceptualisation of memory taxonomies but has not been replicated. Here, healthy adult participants (N = 125) completed a word list and motor sequence task in counterbalanced order with either a shared or distinct sequence structure. In contrast to Mosha & Robertson (2016), we found that a shared ordinal structure between the declarative and motor sequence tasks did not facilitate performance. Overall, our results challenge the robustness of cross-domain generalisation, and underscore the complexity of cross-memory interactions.

neuroscience↗

bioRxiv2024

Supplementary motor area disinhibition during motor sequence learning: A TMS-EEG study

BackgroundIn primary motor cortex, changes in excitatory and inhibitory neurotransmission (E:I balance) accompany motor sequence learning. In particular, there is an early reduction in inhibition (i.e., disinhibition). The supplementary motor area (SMA) is a key brain region involved in the learning of sequences, however the neurophysiological mechanisms within SMA which support motor sequence learning remain poorly understood. Disinhibition may also occur in SMA, but this possibility remains unexamined. ObjectiveWe investigated disinhibition within SMA during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). MethodsTwenty-nine healthy adults practiced a sequential motor task. TMS-evoked potentials (TEPs) resulting from SMA stimulation were measured with EEG before, during, and after practice. The N45 TEP peak was our primary measure of disinhibition. Furthermore, the slope of aperiodic EEG activity was included as an additional E:I balance measure. ResultsSignificant improvements in task performance (i.e., learning) occurred with practice. We observed smaller N45 amplitudes during early learning relative to baseline (both p < .01), indicative of disinhibition. Intriguingly, aperiodic exponents increased as learning progressed and were associated with greater sequence learning (p < .05). ConclusionOur results show disinhibition within SMA during the planning phase of motor sequence learning and thus provide novel understanding on the neurophysiological mechanisms within higher-order motor cortex that accompany new sequence learning.

neuroscience↗

bioRxiv2021

ATP disrupts lipid binding equilibrium to drive retrograde transport critical for bacterial outer membrane asymmetry

The hallmark of the Gram-negative bacterial envelope is the presence of the outer membrane (OM). The OM is asymmetric, comprising lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet; this critical feature confers permeability barrier function against external insults, including antibiotics. To maintain OM lipid asymmetry, the OmpC-Mla system is believed to remove aberrantly localized PLs from the OM and transport them to the inner membrane (IM). Key to the system in driving lipid trafficking is the MlaFEDB ABC transporter complex in the IM, but mechanistic details, including transport directionality, remain enigmatic. Here, we develop a sensitive point-to-point in vitro lipid transfer assay that allows direct tracking of [14C]-labelled PLs between the periplasmic chaperone MlaC and MlaFEDB reconstituted into nanodiscs. We reveal that MlaC spontaneously transfers PLs to the IM transporter in an MlaD-dependent manner that can be further enhanced by coupled ATP hydrolysis. In addition, we show that MlaD is important for modulating productive coupling between ATP hydrolysis and such retrograde PL transfer. We further demonstrate that spontaneous PL transfer also occurs from MlaFEDB to MlaC, but such anterograde movement is instead abolished by ATP hydrolysis. Our work uncovers a model where PLs reversibly partition between two lipid binding sites in MlaC and MlaFEDB, and ATP binding and/or hydrolysis shift this equilibrium to ultimately drive retrograde PL transport by the OmpC-Mla system. These mechanistic insights will inform future efforts towards discovering new antibiotics against Gram-negative pathogens. Significance StatementBiological membranes define cellular boundaries, allow compartmentalization, and represent a prerequisite for life. In Gram-negative bacteria, the outer membrane (OM) prevents entry of toxic substances, conferring intrinsic resistance against many antibiotics. This barrier function requires unequal distribution of lipids across the OM bilayer, yet how such lipid asymmetry is maintained is not well understood. In this study, we established the directionality of lipid transport for a conserved membrane protein complex, and uncovered mechanistic insights into how ATP powers such transport from the OM to the inner membrane. Our work provides fundamental understanding of lipid trafficking within the Gram-negative double-membrane envelope in the context of OM lipid asymmetry, and highlights the importance of targeting lipid transport processes for future antibiotics development.

biochemistry↗