How an odor is perceived is to a large extent dependent on the context in which that odor is (or has been) experienced. For example, experiencing an odor in mixture with taste during consumption can instill taste qualities in the percept of that odor (e.g., vanilla, an odor, has a gustatory quality: sweet). How associative features of odors are encoded in the brain remains unknown, but previous work suggests an important role for ongoing interactions between piriform cortex and extraolfactory systems. Here, we tested the hypothesis that piriform cortex dynamically encodes taste associations of odors. Rats were trained to associate one of two odors with saccharin; the other odor remained neutral. Before and after training, we tested preferences for the saccharin-associated odor versus the neutral odor, and recorded spiking responses from ensembles of neurons in posterior piriform cortex (pPC) to intraoral delivery of small drops of the same odor solutions. The results show that animals successfully learned ...

State-of-the-art all-optical systems promise unprecedented access to neural activity in vivo , using multiphoton optogenetics to allow simultaneous imaging and control of activity in selected neurons at cellular resolution. However, to achieve wide use of all-optical stimulation and imaging, simple strategies are needed to robustly and stably express opsins and indicators in the same cells. Here, we describe a bicistronic adeno-associated virus (AAV) that expresses both the fast and bright calcium indicator jGCaMP8s, and a soma-targeted (st) and two-photon-activatable opsin, ChrimsonR. With this method, stChrimsonR stimulation with two-photon holography in the visual cortex of mice drives robust spiking in targeted cells, and neural responses to visual sensory stimuli and spontaneous activity are strong and stable. Cells expressing this bicistronic construct show responses to both photostimulation and visual stimulation that are similar to responses measured from cells expressing the same opsin and indicat...

Persistent neuronal firing is often observed in working memory and temporal association tasks both in humans and animals, and is believed to retain necessary information in these tasks. We have reported that hippocampal CA1 pyramidal cells are able to support persistent firing through intrinsic mechanisms in the presence of cholinergic agonists. However, it still remains largely unknown how persistent firing is affected by the development of animals and aging. Using in vitro patch-clamp recordings from CA1 pyramidal cells in rat brain slices, we first show that the cellular excitability of these aged rats was significantly lower than that of the young rats, responding with fewer spikes to current injection. In addition, we found age-dependent modulations of input resistance, membrane capacitance, and spike width. However, persistent firing in aged (approximately two-year-old) rats was as strong as that in young animals, and the properties of persistent firing were very similar among different age groups. I...

Wallerian degeneration (WD) occurs in the early stages of numerous neurologic disorders, and clarifying WD pathology is crucial for the advancement of neurologic therapies. ATP is acknowledged as one of the key pathologic substances in WD. The ATP-related pathologic pathways that regulate WD have been defined. The elevation of ATP levels in axon contributes to delay WD and protects axons. However, ATP is necessary for the active processes to proceed WD, given that WD is stringently managed by auto-destruction programs. But little is known about the bioenergetics during WD. In this study, we made sciatic nerve transection models for GO-ATeam2 knock-in rats and mice. We presented the spatiotemporal ATP distribution in the injured axons with in vivo ATP imaging systems, and investigated the metabolic source of ATP in the distal nerve stump. A gradual decrease in ATP levels was observed before the progression of WD. In addition, the glycolytic system and monocarboxylate transporters (MCTs) were activated in Sc...

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...

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...

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,...

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...