Visual recognition is heralded by shifts in local field potential oscillations and inhibitory networks in primary visual cortex

Stimulus-selective response plasticity (SRP) is a robust and lasting modification of primary visual cortex (V1) that occurs in response to exposure to novel visual stimuli. It is readily observed as a pronounced increase in the magnitude of visual evoked potentials (VEPs) recorded in response to phase-reversing grating stimuli in neocortical layer 4. The expression of SRP at the individual neuron level is equally robust, but the qualities vary depending on the neuronal type and how activity is measured. This form of plasticity is highly selective for stimulus features such as stimulus orientation, spatial frequency, and contrast. Several key insights into the significance and underlying mechanisms of SRP have recently been made. First, it occurs concomitantly and shares core mechanisms with behavioral habituation, indicating that SRP reflects the formation of long-term familiarity that can support recognition of innocuous stimuli. Second, SRP does not manifest within a recording session but only emerges after an off-line period of several hours that includes sleep. Third, SRP requires not only canonical molecular mechanisms of Hebbian synaptic plasticity within V1, but also the opposing engagement of two key subclasses of cortical inhibitory neuron: the parvalbumin- and somatostatin-expressing GABAergic interneurons. Fourth, pronounced shifts in the power of cortical oscillations from high frequency (gamma) to low frequency (alpha/beta) oscillations provide respective readouts of the engagement of these inhibitory neuronal subtypes following familiarization. In this article we will discuss the implications of these findings and the outstanding questions that remain to gain a deeper understanding of this striking form of experience-dependent plasticity.

BackgroundSleep deprivation impairs learning, causes stress, and can lead to death. Notch and JNK-1 pathways impact C. elegans sleep in complex ways; these have been hypothesized to involve compensatory sleep. C. elegans DAF-16, a FoxO transcription factor, is required for homeostatic response to decreased sleep and DAF-16 loss decreases survival after sleep bout deprivation. Here, we investigate connections between these pathways and the requirement for sleep after mechanical stress.ResultsReduced function of Notch ligand LAG-2 or JNK-1 kinase resulted in increased time in sleep bouts during development. These animals were inappropriately easy to arouse using sensory stimulation, but only during sleep bouts. This constellation of defects suggested that poor quality sleep bouts in these animals might activate homeostatic mechanisms, driving compensatory increased sleep bouts. Testing this hypothesis, we found that DAF-16 FoxO function was required for increased sleep bouts in animals with defective lag-2 and jnk-1, as loss of daf-16 reduced sleep bouts back to normal levels. However, loss of daf-16 did not suppress arousal thresholds defects. Where DAF-16 function was required differed; in lag-2 and jnk-1 animals, daf-16 function was required in neurons or muscles, respectively, suggesting that disparate tissues can drive a coordinated response to sleep need. Sleep deprivation due to mechanical stimulation can cause death in many species, including C. elegans, suggesting that sleep is essential. We found that loss of sleep bouts in C. elegans due to genetic manipulation did not impact their survival, even in animals lacking DAF-16 function. However, we found that sleep bout deprivation was often fatal when combined with the concurrent stress of mechanical stimulation.ConclusionsTogether, these results in C. elegans confirm that Notch and JNK-1 signaling are required to achieve normal sleep depth, suggest that DAF-16 is required for increased sleep bouts when signaling decreases, and that failure to enter sleep bouts is not sufficient to cause death in C. elegans, unless paired with concurrent mechanical stress. These results suggest that mechanical stress may directly contribute to death observed in previous studies of sleep deprivation and/or that sleep bouts have a uniquely restorative role in C. elegans sleep.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0408-1) contains supplementary material, which is available to authorized users.

Filtering out familiar, irrelevant stimuli eases the computational burden on the cerebral cortex. Inhibition is a candidate mechanism in this filtration process. Oscillations in the cortical local field potential (LFP) serve as markers of the engagement of different inhibitory neurons. In awake mice, we find pronounced changes in LFP oscillatory activity present in layer 4 of primary visual cortex (V1) with progressive stimulus familiarity. Over days of repeated stimulus presentation, low frequency (alpha/beta ∼15 Hz peak) power increases while high frequency (gamma ∼65 Hz peak) power decreases. This high frequency activity re-emerges when a novel stimulus is shown. Thus, high frequency power is a marker of novelty while low frequency power signifies familiarity. Two-photon imaging of neuronal activity reveals that parvalbumin-expressing inhibitory neurons disengage with familiar stimuli and reactivate to novelty, consistent with their known role in gamma oscillations, whereas somatostatin-expressing inhibitory neurons show opposing activity patterns, indicating a contribution to the emergence of lower frequency oscillations. We also reveal that stimulus familiarity and novelty have differential effects on oscillations and cell activity over a shorter timescale of seconds. Taken together with previous findings, we propose a model in which two interneuron circuits compete to drive familiarity or novelty encoding.