Biology subjects

Reynolds, J. P.

Publications and source records attributed to Reynolds, J. P..

5 recordsLinked to original sources

bioRxiv2026

Sensory experience drives glutamate spillover, presynaptic LTP and functional connectome remodeling in the barrel cortex

Information handling and storage by neural circuits is thought to involve dynamic changes in the synaptic connectome, yet how this process unfolds at the level of individual synapses in vivo remains unclear. We took advantage of a well-defined thalamocortical anatomical framework to monitor identifiable individual synapses in barrel cortex during rhythmic whisker stimulation (RWS). Multiplexed ratiometric readouts from genetically targeted optical sensors showed that RWS-induced long-term potentiation (LTP) increased glutamate release per action potential in RWS-responsive axons while recruiting previously silent thalamocortical connections. Fast high-resolution imaging revealed pronounced inter-synaptic glutamate transients and global extracellular GABA waves triggered by brief RWS. LTP induction had no detectable effect on the evoked GABA signal but further enhanced glutamate crosstalk beyond thalamocortical synapses. Strikingly, neural-network simulations suggest that such volume-transmitted excitatory signals can improve associative memory retrieval in sparsely connected networks. Together, these findings uncover key plasticity features of the cortical synaptic connectome and point to a potential computational consequence of glutamate spillover for brain circuit function.

neuroscience↗

bioRxiv2022

Pliable synaptic fidelity and excitatory inter-synaptic crosstalk in the intact brain

Memory formation in neural circuits may involve changes in synaptic efficacy and in cell intrinsic excitability, yet how this process unfolds in the living brain has remained elusive. Here, we employed multiplexed imaging of genetically encoded indicators of glutamate and Ca2+ in mouse barrel cortex to detect increased fidelity coupled with reduced excitation of thalamocortical connections that undergo whisker-stimulation induced LTP. High-resolution imaging revealed that whisker stimuli trigger excitatory synaptic activity that generates extrasynaptic glutamate transients reaching the bulk of neighbouring synapses in the target cortical area. Our findings pave the way to understanding basic plasticity features of the synaptic connectome while revealing a significant component of volume-transmitted glutamatergic signalling among cells in the intact brain. One Sentence SummarySensory-stimulation LTP increases fidelity while reducing excitation at individual thalamocortical connections which generate spatially intersecting glutamate discharges

neuroscience↗

bioRxiv2020

Release probability increases towards distal dendrites boosting high-frequency signal transfer

Dendritic integration of synaptic inputs entangles their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during sustained network activity the influence of individual synapses depends on their release properties. How these properties are distributed along dendrites remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the within-branch position. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.

neuroscience↗

bioRxiv2018

Multiplexed calcium imaging of single-synapse activity and astroglial responses in the intact brain

All-optical registration of neuronal and astrocytic activities within the intact mammalian brain has improved significantly with recent advances in optical sensors and biophotonics. However, relating single-synapse release events and local astroglial responses to sensory stimuli in an intact animal has not hitherto been feasible. Here, we present a multiplexed multiphoton excitation imaging approach for assessing the relationship between presynaptic Ca2+ entry at thalamocortical axonal boutons and perisynaptic astrocytic Ca2+ elevations, induced by whisker stimulation in the barrel cortex of C57BL/6 mice. We find that, unexpectedly, Ca2+ elevations in the perisynaptic astrocytic regions consistently precede local presynaptic Ca2+ signals during spontaneous brain activity associated with anaesthesia. The methods described here can be adapted to a variety of optical sensors and are compatible with experimental designs that might necessitate repeated sampling of single synapses over a longitudinal behavioural paradigm.\n\nHighlightsO_LIWe applied multiplexed multiphoton imaging to optically assess activity of individual synapses and the surrounding astroglia in the intact brain\nC_LIO_LIPerisynaptic astrocytic regions display localiased, context-dependent Ca2+ elevations in vivo\nC_LIO_LISuch elevations may precede spontaneous Ca2+ entry at presynaptic boutons\nC_LIO_LIThis method paves the way for optical investigation of glutamate release probability in vivo\nC_LI

neuroscience↗

bioRxiv2018

Biophysical underpinning of astroglial physiology probed with realistic cell models

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K+ redistribution, key Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.

neuroscience↗