Sublinear integration underlies binocular processing in primary visual cortex

Although we know much about the capacity of neurons to integrate synaptic inputs in vitro, less is known about synaptic integration in vivo. Here we address this issue by investigating the integration of inputs from the two eyes in mouse primary visual cortex. We find that binocular inputs to layer 2/3 pyramidal neurons are integrated sublinearly in an amplitude-dependent manner. Sublinear integration was greatest when binocular responses were largest, as occurs at the preferred orientation and binocular disparity, and highest contrast. Using voltage-clamp experiments and modeling, we show that sublinear integration occurs postsynaptically. The extent of sublinear integration cannot be accounted for solely by nonlinear integration of excitatory inputs, even when they are activated closely in space and time, but requires balanced recruitment of inhibition. Finally, we show that sublinear binocular integration acts as a divisive form of gain control, linearizing the output of binocular neurons and enhancing orientation selectivity.NHMR

Do Mice Habituate to “Gentle Handling?” A Comparison of Resting Behavior, Corticosterone Levels and Synaptic Function in Handled and Undisturbed C57BL/6J Mice

Study Objectives: "Gentle handling" has become a method of choice for 4-6 h sleep deprivation in mice, with repeated brief handling applied before sleep deprivation to induce habituation. To verify whether mice do indeed habituate was assess how 6 days of repeated brief handling impact on resting behavior, on stress, and on the subunit content of N-methyl-D-aspartate receptors (NMDARs) at hippocampal synapases, which is altered by sleep loss. We discuss whether repeated handling biases the outcome of subsequent sleep deprivation.Design: Adult C5BL/6J mice, maintained on a 12 h-12 h light-dark cycle, were left undistrubed for 3 days, then handled during 3 min daily for 6 days in the middle of the light phase. Mice were continuously monitored for their resting time serum conticosterona levels and synaptic NMDAR subunit composition were quantified.Results: Handling caused a similar to 25% reduction of resting time throughtout all handling days, After six, but not after one day of handling, mice had elevated serum corticosterone levels. Six-day handling augmented the presence of the NR2A subunit of NMDARs at hippocampal synapses.Conclusion: Repeated handling induces behavoir and neurochemical alterations that are absent in undisturbed animals. The presistently reduced resting time and the delayed increase in conticosterone levels indicate that mice do not habituate to handling over a 1-week period. Handling-induced modifications bias effects of gentle handling-induced sleep deprivation on sleep homeostasis, stress, glutamate receptor composition and signaling. A standardization of sleep deprivation procedures involving gengle handling will be important for unequivocally specifying how acute sleep loss affects brain function

Do mice habituate to "gentle handling"? A comparison of resting behavior, corticosterone levels and synaptic function in handled and undisturbed C57BL/6J mice

Study Objectives: "Gentle handling" has become a method of choice for 4-6 h sleep deprivation in mice, with repeated brief handling applied before sleep deprivation to induce habituation. To verify whether mice do indeed habituate, we assess how 6 days of repeated brief handling impact on resting behavior, on stress, and on the subunit content of N-methyl-D-aspartate receptors (NMDARs) at hippocampal synapses, which is altered by sleep loss. We discuss whether repeated handling biases the outcome of subsequent sleep deprivation. Design: Adult C57BL/6J mice, maintained on a 12 h-12 h light-dark cycle, were left undisturbed for 3 days, then handled during 3 min daily for 6 days in the middle of the light phase. Mice were continuously monitored for their resting time. Serum corticosterone levels and synaptic NMDAR subunit composition were quantified. Results: Handling caused a ∼25% reduction of resting time throughout all handling days. After six, but not after one day of handling, mice had elevated serum corticosterone levels. Six-day handling augmented the presence of the NR2A subunit of NMDARs at hippocampal synapses. Conclusion: Repeated handling induces behavioral and neurochemical alterations that are absent in undisturbed animals. The persistently reduced resting time and the delayed increase in corticosterone levels indicate that mice do not habituate to handling over a 1-week period. Handling-induced modifications bias effects of gentle handling-induced sleep deprivation on sleep homeostasis, stress, glutamate receptor composition and signaling. A standardization of sleep deprivation procedures involving gentle handling will be important for unequivocally specifying how acute sleep loss affects brain function