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Information processing performed by any system can be conceptually decomposed into the transfer, storage and modification of information—an idea dating all the way back to the work of Alan Turing. However, formal information theoretic definitions until very recently were only available for information transfer and storage, not for modification. This has changed with the extension of Shannon information theory via the decomposition of the mutual information between inputs to and the output of a process into unique, shared and synergistic contributions from the inputs, called a partial information decomposition (PID). The synergistic contribution in particular has been identified as the basis for a definition of information modification. We here review the requirements for a functional definition of information modification in neuroscience, and apply a recently proposed measure of information modification to investigate the developmental trajectory of information modification in a culture of neurons vitro, using partial information decomposition. We found that modification rose with maturation, but ultimately collapsed when redundant information among neurons took over. This indicates that this particular developing neural system initially developed intricate processing capabilities, but ultimately displayed information processing that was highly similar across neurons, possibly due to a lack of external inputs. We close by pointing out the enormous promise PID and the analysis of information modification hold for the understanding of neural systems
Nerve tissue contains a high density of chemical synapses, about 1 per µm3 in the mammalian cerebral cortex. Thus, even for small blocks of nerve tissue, dense connectomic mapping requires the identification of millions to billions of synapses. While the focus of connectomic data analysis has been on neurite reconstruction, synapse detection becomes limiting when datasets grow in size and dense mapping is required. Here, we report SynEM, a method for automated detection of synapses from conventionally en-bloc stained 3D electron microscopy image stacks. The approach is based on a segmentation of the image data and focuses on classifying borders between neuronal processes as synaptic or non-synaptic. SynEM yields 97% precision and recall in binary cortical connectomes with no user interaction. It scales to large volumes of cortical neuropil, plausibly even whole-brain datasets. SynEM removes the burden of manual synapse annotation for large densely mapped connectomes.
Retinal OFF bipolar cells show distinct connectivity patterns with photoreceptors in the wild-type mouse retina. Some types are cone-specific while others penetrate further through the outer plexiform layer (OPL) to contact rods in addition to cones. To explore dendritic stratification of OFF bipolar cells in the absence of rods, we made use of the ‘cone-full’ Nrl-/- mouse retina in which all photoreceptor precursor cells commit to a cone fate including those which would have become rods in wild-type retinas. The dendritic distribution of OFF bipolar cell types was investigated by confocal and electron microscopic imaging of immunolabeled tissue sections. The cells’ dendrites formed basal contacts with cone terminals and expressed the corresponding glutamate receptor subunits at those sites, indicating putative synapses. All of the four analyzed cell populations showed distinctive patterns of vertical dendritic invasion through the OPL. This disparate behavior of dendritic extension in an environment containing only cone terminals demonstrates type-dependent specificity for dendritic outgrowth in OFF bipolar cells: rod terminals are not required for inducing dendritic extension into distal areas of the OPL.
Criticality meets learning : criticality signatures in a self-organizing recurrent neural network
(2017)
Many experiments have suggested that the brain operates close to a critical state, based on signatures of criticality such as power-law distributed neuronal avalanches. In neural network models, criticality is a dynamical state that maximizes information processing capacities, e.g. sensitivity to input, dynamical range and storage capacity, which makes it a favorable candidate state for brain function. Although models that self-organize towards a critical state have been proposed, the relation between criticality signatures and learning is still unclear. Here, we investigate signatures of criticality in a self-organizing recurrent neural network (SORN). Investigating criticality in the SORN is of particular interest because it has not been developed to show criticality. Instead, the SORN has been shown to exhibit spatio-temporal pattern learning through a combination of neural plasticity mechanisms and it reproduces a number of biological findings on neural variability and the statistics and fluctuations of synaptic efficacies. We show that, after a transient, the SORN spontaneously self-organizes into a dynamical state that shows criticality signatures comparable to those found in experiments. The plasticity mechanisms are necessary to attain that dynamical state, but not to maintain it. Furthermore, onset of external input transiently changes the slope of the avalanche distributions – matching recent experimental findings. Interestingly, the membrane noise level necessary for the occurrence of the criticality signatures reduces the model’s performance in simple learning tasks. Overall, our work shows that the biologically inspired plasticity and homeostasis mechanisms responsible for the SORN’s spatio-temporal learning abilities can give rise to criticality signatures in its activity when driven by random input, but these break down under the structured input of short repeating sequences.
A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3°−3.7°) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.
Ocular gene therapy approaches have been developed for a variety of different diseases. In particular, clinical gene therapy trials for RPE65 mutations, X-linked retinoschisis, and choroideremia have been conducted at different centers in recent years, showing that adeno-associated virus (AAV)-mediated gene therapy is safe, but limitations exist as to the therapeutic benefit and long-term duration of the treatment. The technique of vector delivery to retinal cells relies on subretinal injection of the vector solution, causing a transient retinal detachment. Although retinal detachments are known to cause remodeling of retinal neuronal structures as well as significant cell loss, the possible effects of this short-term therapeutic retinal detachment on retinal structure and circuitry have not yet been studied in detail. In this study, retinal morphology and apoptotic status were examined in healthy rat retinas following AAV-mediated gene transfer via subretinal injection with AAV2/5.CMV.d2GFP or sham injection with fluorescein. Outer plexiform layer (OPL) morphology was assessed by immunohistochemical labeling, laser scanning confocal microscopy, and electron microscopy. The number of synaptic contacts in the OPL was quantified after labeling with structural markers. To assess the apoptotic status, inflammatory and pro-apoptotic markers were tested and TUNEL assay for the detection of apoptotic nuclei was performed. Pre- and postsynaptic structures in the OPL, such as synaptic ribbons or horizontal and bipolar cell processes, did not differ in size or shape in injected versus non-injected areas and control retinas. Absolute numbers of synaptic ribbons were not altered. No signs of relevant gliosis were detected. TUNEL labeling of retinal cells did not vary between injected and non-injected areas, and apoptosis-inducing factor was not delocalized to the nucleus in transduced areas. The neuronal circuits in the OPL of healthy rat retinas undergoing AAV-mediated gene transfer were not altered by the temporary retinal detachment caused by subretinal injection, the presence of viral particles, or the expression of green fluorescent protein as a transgene. This observation likely requires further investigations in the dog model for RPE65 deficiency in order to determine the impact of RPE65 transgene expression on diseased retinas in animals and men.