Functional mapping of brain synapses by the enriching activity-marker SynaptoZip

Abstract

Ideally, elucidating the role of specific brain circuits in animal behavior would require the ability to measure activity at all involved synapses, possibly with unrestricted field of view, thus even at those boutons deeply located into the brain. Here, we introduce and validate an efficient scheme reporting synaptic vesicle cycling in vivo. This is based on SynaptoZip, a genetically encoded molecule deploying in the vesicular lumen a bait moiety designed to capture upon exocytosis a labeled alien peptide, Synbond. The resulting signal is cumulative and stores the number of cycling events occurring at individual synapses. Since this functional signal is enduring and measurable both online and ex post, SynaptoZip provides a unique method for the analysis of the history of synaptic activity in regions several millimeters below the brain surface. We show its broad applicability by reporting stimulus-evoked and spontaneous circuit activity in wide cortical fields, in anesthetized and freely moving animals.

Does the posteromedial cortex play a primary role for the capacity for consciousness in rats?

“…HF oscillations are usually associated with tonic neuronal firing (Steriade, Amzica and Contreras, 1996;Steriade, Timofeev and Grenier, 2001;Mukovski et al, 2007) and cortical activation (Fernandez et al, 2017;Siclari et al, 2017;Poulet and Crochet, 2018). Thus, the observed increase in HF power is consistent with the enhanced presynaptic release occurring after ketamine administration (Ferro et al, 2017), and with the idea that ketamine might mainly inhibit GABAergic interneurons, resulting in a state of overall cortical excitation (Seamans, 2008). Interestingly, LF power also increased from wakefulness to ketamine anaesthesia in a dose dependent manner (Fig.…”

General anaesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats

“…Indeed, HF suppression is a more direct indication of reduced neuronal activation relative to ongoing activity, and does not necessarily indicate neuronal hyperpolarization, which can be observed only by intracellular recordings. For example, a coordinated reduction in presynaptic release might also produce an OFF period in the EEG, if compared to the enhanced spontaneous activity that is typically induced by ketamine 49,50 , without implying hyperpolarization.…”

General Anesthesia Disrupts Complex Cortical Dynamics in Response to Intracranial Electrical Stimulation in Rats

“…Indeed, HF suppression is a more direct indication of reduced neuronal activation relative to ongoing activity, and does not necessarily indicate neuronal hyperpolarization, which can be observed only by intracellular recordings. For example, a coordinated reduction in presynaptic release might also produce an OFF period in the EEG, if compared to the enhanced spontaneous activity that is typically induced by ketamine (Brown et al, 2010;Ferro et al, 2017), without implying hyperpolarization. Although our data cannot yet resolve this issue, they illustrate the need for intracellular recordings to determine the role of bistability in the interruption of complex dynamics.…”