Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

When visual contrast changes, retinal ganglion cells adapt by adjusting their sensitivity as well as their temporal filtering characteristics. The latter has classically been described by contrast-induced gain changes that depend on temporal frequency. Here, we explored a new perspective on contrast-induced changes in temporal filtering by using spike-triggered covariance analysis to extract multiple parallel temporal filters for individual ganglion cells. Based on multielectrode-array recordings from ganglion cells in the isolated salamander retina, we found that contrast adaptation of temporal filtering can largely be captured by contrast-invariant sets of filters with contrast-dependent weights. Moreover, differences among the ganglion cells in the filter sets and their contrast-dependent contributions allowed us to phenomenologically distinguish three types of filter changes. The first type is characterized by newly emerging features at higher contrast, which can be reproduced by computational models that contain response-triggered gain-control mechanisms. The second type follows from stronger adaptation in the Off pathway as compared to the On pathway in On-Off-type ganglion cells. Finally, we found that, in a subset of neurons, contrast-induced filter changes are governed by particularly strong spike-timing dynamics, in particular by pronounced stimulus-dependent latency shifts that can be observed in these cells. Together, our results show that the contrast dependence of temporal filtering in retinal ganglion cells has a multifaceted phenomenology and that a multi-filter analysis can provide a useful basis for capturing the underlying signal-processing dynamics

The effects of hypoxia and hypercapnia on hamster activity rhythms

grantor: University of TorontoGolden hamsters (Mesocricetus auratus) were exposed to 3 h of constant hypoxia (O\sb2 concentration = 5%), episodic hypoxia (O\sb2 concentration 17-5%), or constant hypercapnia (CO\sb2 concentration = 15%) at CT6, CT11 and/or CT15 to determine if a phase shift in circadian activity rhythms is induced by a respiratory stimulus. Hamsters were kept in a 14:10 LD cycle before the pulse and at the onset of a respiratory stimulus were released into constant darkness (DD). A separate experiment measuring metabolism oxygen consumption and inspiratory ventilation using open flow respirometry and whole-body plethysmography, respectively, demonstrated that all chemical stimuli were powerful respiratory stimuli. Constant hypoxia caused 0.2 h, 0.3 h, 0.4 h phase delays in hamster activity rhythms at CT6, CT11 and CT15, respectively, when the first day post pulse was used to calculate phase shifts. However, when the constant hypoxia experiment was repeated at CT6 and a post-pulse regression line was used to calculate the phase shift no phase change was induced. Constant hypoxia given on 3 consecutive days at CT6 caused a 0.68 h phase delay using both calculation methods. Episodic hypoxia caused a 0.16 h phase delay at CT15. Hypercapnia did not alter activity rhythms. Apparent phase delays obtained using the first day post pulse for phase shift calculation were strongly correlated with reductions in activity levels on the day of the pulse. These results suggest that the phase delays in activity rhythm induced by the different kinds of hypoxia are mediated by acute decreases in activity levels. It is concluded that respiratory stimuli have little or no direct influence on activity rhythms in activity in hamsters. Episodic hypoxia did not induce long term facilitation (LTF) or phase advances as hypothesized. (Abstract shortened by UMI.)M.Sc

Visual physiology of the layer 4 cortical circuit in silico.

Despite advances in experimental techniques and accumulation of large datasets concerning the composition and properties of the cortex, quantitative modeling of cortical circuits under in-vivo-like conditions remains challenging. Here we report and publicly release a biophysically detailed circuit model of layer 4 in the mouse primary visual cortex, receiving thalamo-cortical visual inputs. The 45,000-neuron model was subjected to a battery of visual stimuli, and results were compared to published work and new in vivo experiments. Simulations reproduced a variety of observations, including effects of optogenetic perturbations. Critical to the agreement between responses in silico and in vivo were the rules of functional synaptic connectivity between neurons. Interestingly, after extreme simplification the model still performed satisfactorily on many measurements, although quantitative agreement with experiments suffered. These results emphasize the importance of functional rules of cortical wiring and enable a next generation of data-driven models of in vivo neural activity and computations

Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex.

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings