Disruption of layer-specific visual processing in a model of focal neocortical epilepsy

The epileptic brain is the result of a sequence of events transforming normal neuronal populations into hyperexcitable networks supporting recurrent seizure generation. These modifications are known to induce fundamental alterations of circuit function and, ultimately, of behavior. However, how hyperexcitability affects information processing in cortical sensory circuits is not yet fully understood. Here, we investigated interlaminar alterations in sensory processing of the visual cortex in a mouse model of focal epilepsy. We found three main circuit dynamics alterations in epileptic mice: (i) a spreading of visual contrast-driven gamma modulation across layers, (ii) an increase in firing rate that is layer-unspecific for excitatory units and localized in infragranular layers for inhibitory neurons, and (iii) a strong and contrast-dependent locking of firing units to network activity. Altogether, our data show that epileptic circuits display a functional disruption of layer-specific organization of visual sensory processing, which could account for visual dysfunction observed in epileptic subjects. Understanding these mechanisms paves the way to circuital therapeutic interventions for epilepsy.

Tight Coupling of Astrocyte pH Dynamics to Epileptiform Activity Revealed by Genetically Encoded pH Sensors

Henry Markram

Astrocytes can both sense and shape the evolution of neuronal network activity and are known to possess unique ion regulatory mechanisms. Here we explore the relationship between astrocytic intracellular pH dynamics and the synchronous network activity that occurs during seizure-like activity. By combining confocal and two-photon imaging of genetically encoded pH reporters with simultaneous electrophysiological recordings, we perform pH measurements in defined cell populations and relate these to ongoing network activity. This approach reveals marked differences in the intracellular pH dynamics between hippocampal astrocytes and neighboring pyramidal neurons in rodent in vitro models of epilepsy. With three different genetically encoded pH reporters, astrocytes are observed to alkalinize during epileptiform activity, whereas neurons are observed to acidify. In addition to the direction of pH change, the kinetics of epileptiform-associated intracellular pH transients are found to differ between the two cell types, with astrocytes displaying significantly more rapid changes in pH. The astrocytic alkalinization is shown to be highly correlated with astrocytic membrane potential changes during seizure-like events and mediated by an electrogenic Na+/HCO3- cotransporter. Finally, comparisons across different cell-pair combinations reveal that astrocytic pH dynamics are more closely related to network activity than are neuronal pH dynamics. This work demonstrates that astrocytes exhibit distinct pH dynamics during periods of epileptiform activity, which has relevance to multiple processes including neurometabolic coupling and the control of network excitability.

Soc Neuroscience2016

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

Alexandros Kyriakatos, Céline Matéo, Carl Petersen, Varun Sreenivasan

The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

SPIE-Intl Soc Optical Eng2017

Sensory memory in a model of a cortical column

Julien Mayor

Sensory memory is the first step of a complex memorization process. Sensory information is buffered in a "sensory store" for a short period. Then part of it is transferred to working memory, where information can be actively processed and, eventually, through its rehearsal, can be memorized and stored in long-term memory. Sensory memory is characterized by a high capacity and a short temporal extension. In this work we show that such a transient buffering of information is well captured in models of cortical microcircuits. Sensory information stays for a short time in the perturbations it induced to the neural activity. Two fundamental characteristics of cortical columns appear to be useful to this purpose. The first one is an approximate balance of neuronal excitation and inhibition. The second one is the sparseness of cells recurrent connections. Together, these two discriminants ensure a broad set of complex dynamical behaviours of the neural network along with the presence of a phase of sustained non-oscillatory activity with very irregular spike trains in individual neurons. We show that at the vicinity of a phase transition from a quiescent state to a phase of chaotic spiking activity, global stimuli can be buffered in the "macroscopic" neuronal activity. However if the sensory input only excites a subpart of the network, efficient information buffering is made using the detailed spiking activity of every neuron in the network. The "microscopic" structure of the network is therefore needed in order to buffer sensory information. In most situations, addition of noise enhances the buffering performance and the computational power of the network. This effect is known in the physical literature as "stochastic resonance". If the network has to achieve complex transformation of its inputs, stochastic resonance is shown to be an emergent property of the population of neurons. Both the very irregular spiking activity present in vivo and the balanced excitation and inhibition measured in cortical columns have a new functional relevance in being the neuronal substrate of an efficient sensory memory .

EPFL2005

Sensory memory in a model of a cortical column

Julien Mayor

EPFL2005