Biology subjects

Papasavvas, C. A.

Publications and source records attributed to Papasavvas, C. A..

3 recordsLinked to original sources

bioRxiv2019

Introducing divisive inhibition in the Wilson-Cowan model

AO_SCPLOWBSTRACTC_SCPLOWBoth subtractive and divisive inhibition has been recorded in cortical circuits and recent findings suggest that different interneuronal populations are responsible for the different types of inhibition. This calls for the formulation and description of these inhibitory mechanisms in computational models of cortical networks. Neural mass and neural field models typically only feature subtractive inhibition. Here, we introduce how divisive inhibition can be incorporated in such models, using the Wilson-Cowan modelling formalism as an example. In addition, we show how the subtractive and divisive modulations can be combined. Including divisive inhibition in neural mass models is a crucial step in understanding its role in shaping oscillatory phenomena in cortical networks.

neuroscience↗

bioRxiv2019

Correction of z-motion artefacts to allow population imaging of synaptic activity in awake behaving mice

Functional imaging of head-fixed, awake, behaving mice using two-photon imaging of fluorescent activity reporters has become a powerful tool in the studying the function of the brain. Motion artefacts are an inevitable problem during such experiments and are routinely corrected for in x and y dimensions. However, axial (z) shifts of several microns can also occur, leading to intensity fluctuations in structures such as synapses that are small compared to the axial point-spread function of the microscope. Here we present a simple strategy to correct z-motion artefacts arising over the course of a time-series experiment in a single optical plane. Displacement in z was calculated using dye-filled blood vessels as an anatomical marker, providing high contrast images and accuracy to within [~]0.1 {micro}m. The axial profiles of ROIs corresponding to synapses were described using a Moffat function and this \"ROI-spread function\" used to correct activity traces on an ROI-by-ROI basis. We demonstrate the accuracy and utility of the procedures in simulation experiments using fluorescent beads and then apply them to correcting measurements of synaptic activity in populations of vasoactive-intestinal peptide (VIP) interneurons expressing the synaptic reporter SyGCaMP6f. Correction of z-motion artefacts had a substantial impact on the apparent correlation between synaptic activity and running speed, demonstrating the importance of correcting for these artefacts for the interpretation of in vivo imaging experiments in awake mice.\n\nSummary of Key PointsO_LIMotion artefacts associated with motor behaviour are an inevitable problem of multiphoton imaging in awake behaving animals, particularly imaging synapses.\nC_LIO_LICorrection of axial motion usually requires volumetric imaging resulting in slower rates of acquisition.\nC_LIO_LIWe describe a method that is easy to implement to correct z-motion artefacts that allows population imaging of synaptic activity while scanning a single plane in a standard multiphoton microscope.\nC_LIO_LIThe method uses a reference volume acquired in two colour channels - an activity reporter and an anatomical marker of blood vessels. The procedure estimates the z-displacement in every frame and applies an intensity correction in which the z point-spread function for each synapse is modelled as a Moffat function.\nC_LIO_LIWe demonstrate that the method allows synaptic calcium activity signals to be collected from populations of synaptic boutons in mouse primary visual cortex during locomotion.\nC_LI

neuroscience↗

bioRxiv2019

The spread of gap-junction mediated activity in neocortex is modulated by extracellular potassium

Parvalbumin-expressing interneurons in cortical networks are coupled by gap-junctions, forming a syncytium that supports propagating epileptiform discharges, induced by 4-aminopyridine. It remains unclear, however, whether these propagating events occur under more natural states, without pharmacological blockade. In particular, we investigated whether propagation also happens when extracellular K+ rises, as is known to occur following intense network activity, such as during seizures. We examined how increasing [K+]o affects the likelihood of propagating activity away from a site of focal (200-400{micro}m) optogenetic activation of PV-interneurons. Activity was recorded using a linear 16-electrode array placed along layer V of primary visual cortex. At baseline levels of [K+]o (3.5mM), induced activity was recorded only within the illuminated area. However, when [K+]o was increased above a threshold level (50th percentile= 8.0mM; interquartile range= 7.5-9.5mM), time-locked, fast-spiking unit activity, indicative of parvalbumin-expressing interneuron firing, was also recorded outside the illuminated area, propagating at 59.1 mm/s. Blockade of glutamatergic synaptic transmission reduced the efficacy of propagation, but could be restored by further increasing [K+]o. Propagation was further reduced, and in most cases prevented altogether, by pharmacological blockade of gap-junctions, achieved by any of three different drugs, quinine, mefloquine or carbenoxolone. Wash-out of quinine rapidly re-established the pattern of propagating activity. Computer simulations show qualitative differences between propagating discharges in high [K+]o and 4-aminopyridine, arising from differences in the electrotonic effects of these two manipulations. These interneuronal syncytial interactions are likely to affect the complex electrographic dynamics of seizures, once [K+]o is raised above this threshold level.\n\nSignificance statementWe demonstrate the spatially extended propagation of activity through a gap-junction mediated syncytium of parvalbumin-expressing interneurons, in conditions that are known to exist at times within the brain. Previous work has only shown gap-junction coordination very locally, through directly connected cells, or induced at a distance by pharmacological means. We show that cell-class specific spread is facilitated by raised extracellular K+. This is highly pertinent to what happens at the onset of, and during, seizures, when extracellular K+ can rise rapidly to levels well in excess of the measured threshold for propagation. Our data suggests that interneuronal coupling will be enhanced at this time, and this has clear implications for the behaviour of these cells as seizures progress.

neuroscience↗