Biology subjects

Smirnakis, S.

Publications and source records attributed to Smirnakis, S..

4 recordsLinked to original sources

bioRxiv2018

Asynchronous suppression of visual cortex during absence seizures

Absence epilepsy is a common childhood disorder featuring frequent cortical spike-wave seizures with a loss of awareness and behavior. Using the calcium indicator GCaMP6 with in vivo 2-photon cellular microscopy and simultaneous electrocorticography, we examined the collective activity profiles of individual neurons and surrounding neuropil across all layers in V1 during spike-wave seizure activity over prolonged periods in stargazer mice. We show that most ([~]80%) neurons in all cortical layers reduce their activity during seizures, whereas a smaller pool activates or remains neutral. Unexpectedly, ictal participation of identified single unit activity is not fixed, but fluctuates on a flexible time scale across seizures. Pairwise correlation analysis of calcium activity reveals a surprising lack of synchrony among neurons and neuropil patches in all layers during seizures. Our results demonstrate an asynchronous suppression of visual cortex during absence seizures, with major implications for understanding cortical network function during EEG states of reduced awareness.

neuroscience↗

bioRxiv2018

Internal gain modulations, but not changes in stimulus contrast, preserve the neural code

Neurons in primary visual cortex (V1) are strongly modulated both by stimulus contrast and by fluctuations of internal inputs. An important question is whether population codes are preserved under these conditions. Changes in stimulus contrast are thought to leave population codes invariant, whereas the effect of internal gain modulations remains unknown. To address these questions we studied how the direction-of-motion of oriented gratings is encoded in layer 2/3 of mouse V1. Surprisingly, we found that, because contrast gain responses across cells are heterogeneous, a change in contrast alters the information distribution profile across cells leading to the failure of contrast invariance. Remarkably, internal input fluctuations that cause commensurate firing rate modulations at the single-cell level, do respect population code invariance. These observations have important implications for visual information encoding, and argue that the brain strives to maintain the stability of the neural code in the face of fluctuating internal inputs.

neuroscience↗

bioRxiv2017

The effect of single pyramidal neuron firing across and within layers in mouse V1

The influence of cortical cell spiking activity on nearby cells has been studied extensively in vitro. Less is known, however, about the impact of single cell firing on local cortical networks in vivo. In a pioneering study, Kwan et al. (Kwan et al., 2012) reported that in mouse layer 2/3 (L2/3), under anesthesia, stimulating a single pyramidal cell recruits ~1.7% of neighboring pyramidal units. Here we employ two-photon calcium imaging, in conjunction with single-cell patch clamp stimulation, to probe, in both the awake and lightly anesthetized states, how i) activating single L2/3 pyramidal neurons recruits neighboring units within L2/3 and from layer 4 (L4) to L2/3, and whether ii) activating single pyramidal neurons changes population activity in local circuit. To do this, it was essential to develop an algorithm capable of quantifying how sensitive the calcium signal is at detecting effectively recruited units (\"followers\"). This algorithm allowed us to estimate the chance of detecting a follower as a function of the probability that an epoch of stimulation elicits one extra action potential (AP) in the follower cell. Using this approach, we found only a small fraction (<0.75%) of L2/3 cells to be significantly activated within a radius of ~200 m from a stimulated neighboring L2/3 pyramidal cell. This fraction did not change significantly in the awake versus the lightly anesthetized state, nor when stimulating L2/3 versus underlying L4 pyramidal neurons. These numbers are in general agreement with, though lower than, the percentage of neighboring cells (2.1%) reported by Kwan et al. to be activated upon stimulating single L2/3 pyramidal neurons under anesthesia (Kwan et al., 2012). Interestingly, despite the small number of individual units found to be reliably driven, we did observe a modest but significant elevation in aggregate population responses compared to sham stimulation. This underscores the distributed impact that single cell stimulation has on neighboring microcircuit responses, revealing only a small minority of relatively strongly connected partners.\n\nOne Sentence SummaryPatch-clamp stimulation in conjunction with 2-photon imaging shows that activating single layer-2/3 or layer-4 pyramidal neurons produces few (<1% of local units) reliable singlecell followers in L2/3 of mouse area V1, either under light anesthesia or in quiet wakefulness: instead, single cell stimulation was found to elevate aggregate population activity in a weak but highly distributed fashion.

neuroscience↗

bioRxiv2017

Visually driven neuropil activity and information encoding in mouse area V1

Spontaneous calcium fluorescence recorded from large cortical neuropil patches strongly correlates with the electro-corticogram, and is thought to arguably reflect primarily pre-synaptic inputs. Here we used in vivo 2-photon imaging with Oregon Green Bapta (OGB) to study neuropil visual responses to moving gratings in layer 2/3 of mouse area V1. We found neuropil responses to be more reliable and more strongly modulated than neighboring somatic activity. Furthermore, stimulus independent modulations in neuropil activity, i.e. noise correlations, were highly coherent across the cortical surface, up to distances of at least 200 m. Pairwise neuropil-to-neuropil-patch noise correlation strength was much higher than cell-to-cell noise correlation strength and depended strongly on brain state, decreasing in quiet wakefulness relative to light anesthesia. The profile of neuropil noise correlation strength decreased gently with distance, dropping by ~12% at a distance of 200 m. This was comparatively slower than the profile of cell-to-cell noise correlations, which dropped by ~30% at 200 m. Interestingly, in spite of the \"salt & pepper\" organization of orientation and direction encoding across mouse V1 neurons, populations of neuropil patches, even of moderately large size (radius ~100m), showed high accuracy for discriminating perpendicularly moving gratings commensurate to the accuracy of corresponding cell populations. These observations underscore the dynamic nature of the functional organization of neuropil activity.\n\nConflict of InterestThe authors declare that no competing interests exist.

neuroscience↗