Our findings suggest a novel approach to treating acute seizures: harnessing synaptogenic molecules to enhance connectivity in the inhibitory network.
Sleep supports the formation of a variety of declarative and non-declarative memories, and sleep deprivation often impairs these types of memories. In human subjects, natural sleep either during a nap or overnight leads to long-lasting improvements in visuomotor and fine motor tasks, but rodent models recapitulating these findings have been scarce. Here we present evidence that 5 hours of acute sleep deprivation impairs mouse skilled reach learning compared to a matched period of ad libitum sleep. In sleeping mice, the duration of total sleep time during the 5 hours of sleep opportunity or during the first bout of sleep did not correlate with ultimate gain in motor performance. In addition, we observed that reversal learning during the skilled reaching task was also affected by sleep deprivation. Consistent with this observation, 5 hours of sleep deprivation also impaired reversal learning in the water-based Y-maze. In conclusion, acute sleep deprivation negatively impacts subsequent motor and reversal learning and memory.
Many sensory neural circuits exhibit response normalization, which occurs when the response of a neuron to a combination of multiple stimuli is less than the sum of the responses to the individual stimuli presented alone. In the visual cortex, normalization takes the forms of cross-orientation suppression and surround suppression. At the onset of visual experience, visual circuits are partially developed and exhibit some mature features such as orientation selectivity, but it is unknown whether cross-orientation suppression is present at the onset of visual experience or requires visual experience for its emergence. We characterized the development of normalization and its dependence on visual experience in female ferrets. Visual experience was varied across the following three conditions: typical rearing, dark rearing, and dark rearing with daily exposure to simple sinusoidal gratings (14-16 h total). Cross-orientation suppression and surround suppression were noted in the earliest observations, and did not vary considerably with experience. We also observed evidence of continued maturation of receptive field properties in the second month of visual experience: substantial length summation was observed only in the oldest animals (postnatal day 90); evoked firing rates were greatly increased in older animals; and direction selectivity required experience, but declined slightly in older animals. These results constrain the space of possible circuit implementations of these features. The development of the brain depends on both nature-factors that are independent of the experience of an individual animal-and nurture-factors that depend on experience. While orientation selectivity, one of the major response properties of neurons in visual cortex, is already present at the onset of visual experience, it is unknown whether response properties that depend on interactions among multiple stimuli develop without experience. We find that the properties of cross-orientation suppression and surround suppression are present at eye opening, and do not depend on visual experience. Our results are consistent with the idea that a majority of the basic properties of sensory neurons in primary visual cortex are derived independent of the experience of an individual animal.
Background: Single-unit recording in Pavlovian conditioning tasks requires the use of within-subject designs as well as sampling a considerable number of trials per trial type and session, which increases the total trial count. Pavlovian conditioning, on the other hand, requires a long average intertrial interval (ITI) relative to cue duration for cue-specific learning to occur. These requirements combined can make the session duration unfeasibly long. New method: To circumvent this issue, we developed a self-initiated variant of the Pavlovian magazine-approach procedure in rodents. Unlike the standard procedure, where the animals passively receive the trials, the selfinitiated procedure grants animals agency to self-administer and self-pace trials from a predetermined, pseudorandomized list. Critically, whereas in the standard procedure the typical ITI is in the order of minutes, our procedure uses a much shorter ITI (10 s).Results: Despite such a short ITI, discrimination learning in the self-initiated procedure is comparable to that observed in the standard procedure with a typical ITI, and superior to that observed in the standard procedure with an equally short ITI. Comparison with existing method(s): The self-initiated procedure permits delivering 100 trials in a ∼1-h session, almost doubling the number of trials safely attainable over that period with the standard procedure. Conclusions: The self-initiated procedure enhances the collection of neural correlates of cue-reward learning while producing good discrimination performance. Other advantages for neural recording studies include ensuring that at the start of each trial the animal is engaged, attentive and in the same location within the conditioning chamber.
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