Trigeminal neurons convey somatosensory information from craniofacial tissues. In mouse brain, ascending projections from medullary trigeminal neurons arrive at taste neurons in the parabrachial (PB) nucleus, suggesting that taste neurons participate in somatosensory processing. However, the cell types that support this convergence were undefined. Using Cre-directed optogenetics and in vivo neurophysiology in anesthetized mice of both sexes, here we studied whether transient receptor potential vanilloid 1 (TRPV1)-lineage nociceptive and thermosensory fibers are primary neurons that drive trigeminal circuits reaching PB taste cells. We monitored spiking activity in individual PB neurons during photoexcitation of the terminals of TRPV1-lineage fibers arriving at the dorsal trigeminal nucleus caudalis, which relays orofacial somatosensory messages to the PB area. We also recorded PB neural responses to oral delivery of taste, chemesthetic, and thermal stimuli. We found that optical excitation of TRPV1-lineage...

Recent research suggests that episodic memory is associated with systematic differences in the localization of neural activity observed during memory encoding and retrieval. The retrieval-related anterior shift is a phenomenon whereby the retrieval of a stimulus event (e.g., a scene image) is associated with a peak neural response which is localized more anteriorly than the response elicited when the stimulus is experienced directly. Here, we examine whether the magnitude of the anterior shift (i.e., the distance between encoding- and retrieval-related response peaks) is moderated by age, and also whether the shift is associated with memory performance. Younger and older human subjects of both sexes underwent fMRI as they completed encoding and retrieval tasks on word-face and word-scene pairs. We localized peak scene and face selectivity for each individual participant within the face-selective precuneus and in three scene-selective (parahippocampal place area [PPA], medial place area, occipital place are...

How sleep leads to offline performance gains in learning remains controversial. A use-dependent model assumes that sleep processing leading to performance gains occurs based on general cortical usage during wakefulness, whereas a learning-dependent model assumes that this processing is specific to learning. Here, we found evidence that supports a learning-dependent model in visual perceptual learning (VPL) in humans (both sexes). First, we measured the strength of spontaneous oscillations during sleep after two training conditions that required the same amount of training or visual cortical usage; one generated VPL (learning condition), while the other did not (interference condition). During a post-training nap, slow-wave activity (SWA) and sigma activity during non-rapid eye movement (NREM) sleep and theta activity during REM sleep were source localized to the early visual areas using retinotopic mapping. Inconsistent with a use-dependent model, only in the learning condition, sigma and theta activity, n...

The brain continues to respond selectively to environmental stimuli during sleep. However, the functional role of such responses, and whether they reflect information processing or rather sensory inhibition, is not fully understood. Here, we present 17 human sleepers (14 females) with their own name and two unfamiliar first names, spoken by either a familiar voice (FV) or an unfamiliar voice (UFV), while recording polysomnography during a full night of sleep. We detect K-complexes, sleep spindles, and microarousals, and assess event-related and frequency responses as well as intertrial phase synchronization to the different stimuli presented during nonrapid eye movement (NREM) sleep. We show that UFVs evoke more K-complexes and microarousals than FVs. When both stimuli evoke a K-complex, we observe larger evoked potentials, more precise time-locking of brain responses in the delta band (1–4 Hz), and stronger activity in the high frequency (>16 Hz) range, in response to UFVs relative to FVs. Crucially, thes...

Overlap between events can lead to interference because of a trade-off between encoding the present event and retrieving the past event. Temporal context information, “when” something occurred, a defining feature of episodic memory, can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference is unclear. Here, by identifying brain states using scalp eEEG from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification anal...

To explore whether the thalamus participates in lexical status (word vs. nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep brain stimulation lead implantation during a visually cued word- and nonword-reading aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time-locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multi-unit spiking activity, occurring shortly before and predominantly time-locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization ...

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice of both sexes while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel: an unbiased, temporally-precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for underst...

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Drosophila . Here we analyze how exposure to a novel stimulus causes override of gustatory (proboscis-extension reflex or “PER”) habituation. While brief sucrose contact with tarsal hairs causes naïve Drosophila to extend their proboscis, persistent exposure reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief...

PEGPH20, a human recombinant hyaluronidase, has been proposed as a coadjutant to pancreatic cancer chemotherapy. In early trials, patients reported increased widespread muscle pain as the main adverse reaction to PEGPH20. To understand how PEGPH20 caused musculoskeletal pain, we systemically administered PEGPH20 to male mice and measured voluntary wheel activity and pain-related behaviors. These were paired with ex vivo electrophysiology of primary sensory neurons, whole DRG real-time PCR, and immunohistochemistry of hindpaw muscle. PEGPH20 induced significantly lower wheel running, compared with vehicle-treated animals, and decreased mechanical withdrawal thresholds 5 d after PEGPH20 injections. Chemo-sensory muscle afferents showed increased responses to noxious chemical stimulation of their receptive fields (RFs) in the PEGPH20-treated group. This was correlated with upregulation of the NGF receptor TrkA, the transient receptor potential vanilloid type 1 (TRPV1) channel and ATP-sensitive channel P2X3 in...

Inducible Cre recombinase facilitates temporal control of genetic recombination in numerous transgenic model systems, a feature which has made it a popular tool for adult neurogenesis studies. One of the most common forms of inducible Cre, CreERT2, requires activation by the selective estrogen receptor modulator tamoxifen (TAM) to initiate recombination of LoxP-flanked sequences. To date, most studies deliver TAM via intraperitoneal injection. But the introduction of TAM-infused commercial chows has recently expanded the possible modes of TAM delivery. Despite the widespread use of TAM-inducible genetic models in adult neurogenesis research, the comparative efficiency and off-target effects of TAM administration protocols is surprisingly infrequently studied. Here, we compare a standard, 5 d TAM injection regimen with voluntary consumption of TAM-infused chow. First, we used adult NestinCreERT2;Rosa-LoxP-STOP-LoxP-EYFP reporter mice to show that two weeks of TAM chow and 5 d of injections led to LoxP recom...