Gain control by layer six in cortical circuits of vision

After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.     

Stargazin modulates AMPA receptor gating and trafficking by distinct domains

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors mediate fast excitatory synaptic transmission in the brain. These ion channels rapidly deactivate and desensitize, which determine the time course of synaptic transmission. Here, we find that the AMPA receptor interacting protein, stargazin, not only mediates AMPA receptor trafficking but also shapes synaptic responses by slowing channel deactivation and desensitization. The cytoplasmic tail of stargazin determines receptor trafficking, whereas the ectodomain controls channel properties. Stargazin alters AMPA receptor kinetics by increasing the rate of channel opening. Disrupting the interaction of stargazin ectodomain with hippocampal AMPA receptors alters the amplitude and shape of synaptic responses, establishing a crucial function for stargazin in controlling the efficacy of synaptic transmission in the brain.     

Prediction,diagnosis, and causal thinking in forecasting

While forecasting involves forward/predictive thinking, it depends crucially on prior diagnosis for suggesting a model of the phenomenon, for defining‘relevant’variables, and for evaluating forecast accuracy via the model. The nature of diagnostic thinking is examined with respect to these activities. We first consider the difficulties of evaluating forecast accuracy without a causal model of what generates outcomes. We then discuss the development of models by considering how attention is directed to variables via analogy and metaphor as well as by what is unusual or abnormal. The causal relevance of variables is then assessed by reference to probabilistic signs called‘cues to causality’. These are: temporal order, constant conjunction, contiguity in time and space, number of alternative explanations, similarity, predictive validity, and robustness. The probabilistic nature of the cues is emphasized by discussing the concept of spurious correlation and how causation does not necessarily imply correlation. Implications for improving forecasting are considered with respect to the above issues.