Biology subjects

Langley, H.

Publications and source records attributed to Langley, H..

3 recordsLinked to original sources

bioRxiv2025

Synaptotagmin-7 is required for synchronous but not asynchronous facilitation of glutamate release at cortical boutons

Short-term synaptic plasticity and the kinetics of neurotransmitter release vary widely across synapses, but population measurements obscure the mechanisms that generate this diversity. While the Ca2+ sensor Synaptotagmin-7 (Syt7) has been implicated in facilitation, vesicle replenishment and asynchronous vesicle exocytosis, its precise contributions to these processes remain debated. We used quantal-resolution imaging to measure synchronous and asynchronous glutamate release at individual cortical boutons in wild type and Syt7-/- neurons. Stratifying boutons by release efficacy and applying failure-based analysis to isolate trials where the first action potential evoked no release allowed us to separate facilitation from vesicle depletion. Syt7 deletion selectively eliminated activity-dependent facilitation of synchronous release but left facilitation of asynchronous release intact, although its overall magnitude was reduced. We further show that synchronous and asynchronous events arise from functionally distinct vesicle populations. These findings demonstrate that activity-dependent facilitation of synchronous and asynchronous exocytosis are mechanistically separable, enabling synapses to independently tune distinct temporal components of neurotransmission.

neuroscience↗

bioRxiv2025

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only species with complete connectomes are worms1-3 and sea squirts4 (103-104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory5,6 and an intricate ventral nerve cord analogous to the vertebrate spinal cord7-11. Here we report the first densely reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized and embodied, reminiscent of distributed control architectures in engineered systems12,13.

neuroscience↗

bioRxiv2021

Asynchronous glutamate exocytosis is enhanced in low release probability synapses and is widely dispersed across the active zone

The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties of neuronal synapses and regulation of neuronal network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using the fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular release in tens to hundreds of individual synaptic outputs (presynaptic boutons) from single pyramidal cells in culture with 4 millisecond temporal resolution, and localise vesicular release sites with ~ 75 nm spatial resolution. We find that the ratio between synchronous and asynchronous synaptic vesicle exocytosis varies extensively among presynaptic boutons supplied by the same axon, and that asynchronous release fraction is elevated in parallel with short-term facilitation at synapses with low release probability. We further demonstrate that asynchronous exocytosis sites are more widely distributed within the presynaptic release area than synchronous sites. These findings are consistent with a model in which functional presynaptic properties are regulated via a synapsespecific adjustment of the coupling distance between presynaptic Ca2+ channels and releaseready synaptic vesicles. Together our results reveal a universal relationship between the two major functional properties of synapses - the timing and the overall probability of neurotransmitter release.

neuroscience↗