Cell birth and survival in the adult hippocampus are regulated by a circadian clock. Rotating shift work and jet lag disrupt circadian rhythms and aggravate disease. Internal misalignment, a state in which abnormal phase relationships prevail between and within organs, is proposed to account for adverse effects of circadian disruption. This hypothesis has been difficult to test because phase shifts of the entraining cycle inevitably lead to transient desynchrony. Thus, it remains possible that phase shifts, regardless of internal desynchrony, account for adverse effects of circadian disruption and alter neurogenesis and cell fate. In order to address this question, we examined cell birth and differentiation in the duper Syrian hamster ( Mesocricetus auratus ), a Cry1 -null mutant in which re-entrainment of locomotor rhythms is greatly accelerated. Adult females were subjected to alternating 8h advances and delays at eight 16-day intervals. BrdU, a cell birth marker, was given midway through the experiment...

Studies of ongoing, rapid motor behaviours have often focused on the decision-making implicit in the task. Here, we instead study how decision-making integrates with the perceptual and motor systems and propose a framework of limited-capacity, pipelined processing with flexible resources to understand rapid motor behaviours. Results from three experiments show that human performance is consistent with our framework: participants perform objectively worse as task difficulty increases and, surprisingly, this drop in performance is largest for the most skilled performers. As well, our analysis shows that the worst-performing participants can perform equally well under increased task demands, which is consistent with flexible neural resources being allocated to reduce bottleneck effects and improve overall performance. We conclude that capacity limits lead to information bottlenecks and that processes like attention help reduce the effects that these bottlenecks have on maximal performance. Significance State...

There is substantial variation in the mean and variance of light levels (luminance and contrast) in natural visual scenes. Retinal ganglion cells maintain their sensitivity despite this variation using two adaptive mechanisms, which control how responses depend on luminance and on contrast. However, the nature of each mechanism and their interactions downstream of the retina are unknown. We recorded neurons in the magnocellular and parvocellular layers of the lateral geniculate nucleus (LGN) in anesthetized adult male macaques and characterized how their responses adapt to changes in contrast and luminance. As contrast increases, neurons in the magnocellular layers maintain sensitivity to high temporal frequency stimuli but attenuate sensitivity to low temporal-frequency stimuli. Neurons in the parvocellular layers do not adapt to changes in contrast. As luminance increases, both magnocellular and parvocellular cells increase their sensitivity to high temporal frequency stimuli. Adaptation to luminance is ...

The highly-conserved stomatin domain has been identified in genes throughout all classes of life. In animals, different stomatin domain-encoding genes have been implicated in the function of the kidney, red blood cells, and specific neuron types, though the underlying mechanisms remain unresolved. In one well-studied example of stomatin domain gene function, the C. elegans gene mec-2 and its mouse homologue Stoml3 are required for the function of mechanosensory neurons, where they modulate the activity of mechanosensory ion channels on the plasma membrane. Here we identify an additional shared function for mec-2 and Stoml3 in a very different sensory context, that of olfaction. In worms, we find that a subset of stomatin domain genes are expressed in olfactory neurons, but only mec-2 is strongly required for olfactory behavior. mec-2 acts cell-autonomously and multiple alternatively-spliced isoforms of mec-2 can be substituted for each other. We generate a Stoml3 knockout mouse and demonstrate that, like i...

The search for molecular underpinnings of human vocal communication has focused on genes encoding forkhead-box transcription factors, as rare disruptions of FOXP1, FOXP2, and FOXP4 have been linked to disorders involving speech and language deficits. In male songbirds, an animal model for vocal learning, experimentally altered expression levels of these transcription factors impair song production learning. The relative contributions of auditory processing, motor function or auditory-motor integration to the deficits observed after different FoxP manipulations in songbirds are unknown. To examine the potential effects on auditory learning and development, we focused on female zebra finches ( Taeniopygia guttata ) that do not sing but develop song memories, which can be assayed in operant preference tests. We tested whether the relatively high levels of FoxP1 expression in forebrain areas implicated in female song preference learning are crucial for the development and/or maintenance of this behavior. Juven...

Shifts in spatial attention are associated with variations in α band (α, 8–14 Hz) activity, specifically in interhemispheric imbalance. The underlying mechanism is attributed to local α-synchronization, which regulates local inhibition of neural excitability, and frontoparietal synchronization reflecting long-range communication. The direction-specific nature of this neural correlate brings forward its potential as a control signal in brain-computer interfaces (BCIs). In the present study, we explored whether long-range α-synchronization presents lateralized patterns dependent on voluntary attention orienting and whether these neural patterns can be picked up at a single-trial level to provide a control signal for active BCI. We collected electroencephalography (EEG) data from a cohort of healthy adults ( n  = 10) while performing a covert visuospatial attention (CVSA) task. The data show a lateralized pattern of α-band phase coupling between frontal and parieto-occipital regions after target presentation,...

Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABAA) inhibition and is approved for treating postpartum depression in women. Although the antidepressant mechanism of AlloP is largely unknown, it could involve selective action at GABAA receptors containing the δ subunit. Despite previous evidence for selective effects of AlloP on α4/δ-containing receptors of hippocampal dentate granule cells (DGCs), other recent results failed to demonstrate selectivity at these receptors ([Lu et al., 2020][1]). In contrast to DGCs, hippocampal fast-spiking parvalbumin (PV) interneurons express an unusual variant partnership of δ subunits with α1 subunits. Here, we hypothesized that native α1/δ receptors in hippocampal fast-spiking interneurons may provide a preferred substrate for AlloP. Contrary to the hypothesis, electrophysiology from genetically tagged PV interneurons in hippocampal slices from male mice showed that 100 nm AlloP promoted phasic inhibition by increasing the sIPSC deca...

Rhodopsin is the critical receptor molecule which enables vertebrate rod photoreceptor cells to detect a single photon of light and initiate a cascade of molecular events leading to visual perception. Recently, it has been suggested that the F45L mutation in the transmembrane helix of rhodopsin disrupts its dimerization in vitro . To determine whether this mutation of rhodopsin affects its signaling properties in vivo , we generated knock-in mice expressing the rhodopsin F45L mutant. We then examined the function of rods in the mutant mice versus wild-type controls, using in vivo electroretinography and transretinal and single cell suction recordings, combined with morphologic analysis and spectrophotometry. Although we did not evaluate the effect of the F45L mutation on the state of dimerization of the rhodopsin in vivo , our results revealed that F45L-mutant mice exhibit normal retinal morphology, normal rod responses as measured both in vivo and ex vivo , and normal rod dark adaptation. We conclude that...

Hippocampal CA1 cells take part in reliable, time-locked activity sequences in tasks that involve an association between temporally separated stimuli, in a manner that tiles the interval between the stimuli. Such cells have been termed time cells. Here, we adopt a first-principles approach to comparing diverse analysis and detection algorithms for identifying time cells. We generated synthetic activity datasets using calcium signals recorded in vivo from the mouse hippocampus using two-photon (2-P) imaging, as template response waveforms. We assigned known, ground truth values to perturbations applied to perfect activity signals, including noise, calcium event width, timing imprecision, hit trial ratio and background (untuned) activity. We tested a range of published and new algorithms and their variants on this dataset. We find that most algorithms correctly classify over 80% of cells, but have different balances between true and false positives, and different sensitivity to the five categories of perturb...

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene Cnih3 have demonstrated estrous-dependent phenotypes in dorsal hippocampal synaptic plasticity, composition, and learning/memory. We therefore profiled dorsal hippocampal transcriptomes from female mice in each estrous cycle stage, and contrasted it with that of males, across wild-type (WT) and Cnih3 mutants. In wild types, we identified only subtle differences in gene expression between the sexes, while comparing estrous stages to one another revealed up to >1000 differentially expressed genes (DEGs). These estrous-responsive genes are especially enriched in gene markers of oligodendrocytes and the dentate gyr...