Sound-level coding in the auditory nerve is achieved through the progressive recruitment of auditory nerve fibers (ANFs) that differ in threshold of activation and in the stimulus level at which the spike rate saturates. To investigate the functional state of the ANFs, the electrophysiological tests routinely used in clinics only capture the first action potentials firing in synchrony at the onset of the acoustic stimulation. Assessment of other properties ( e.g . spontaneous rate and adaptation time constants) requires single-fiber recordings directly from the nerve, which for ethical reasons is not allowed in humans. By combining neuronal activity measurements at the round window and signal-processing algorithms, we constructed a peri-stimulus time response (PSTR), with a waveform similar to the peri-stimulus time histograms (PSTHs) derived from single-fiber recordings in young adult female gerbils. Simultaneous recordings of round-window PSTR and single-fiber PSTH provided models to predict the adaptati...

The neuropeptide oxytocin (Oxt) plays important roles in modulating social behaviors. Oxytocin receptor (Oxtr) is abundantly expressed in the brain and its relationship to socio-behavioral controls has been extensively studied using mouse brains. Several genetic tools to visualize and/or manipulate Oxtr-expressing cells, such as fluorescent reporters and Cre recombinase drivers, have been generated by ES-cell based gene targeting or bacterial artificial chromosome (BAC) transgenesis. However, these mouse lines displayed some differences in their Oxtr expression profiles probably due to the complex context and integrity of their genomic configurations in each line. Here we apply our sophisticated genome-editing techniques to the Oxtr locus, systematically generating a series of knock-in mouse lines, in which its endogenous transcriptional regulations are intactly preserved and evaluate their expression profiles to ensure the reliability of our new tools. We employ the epitope tagging strategy, with which C-...

To understand how vowels are encoded by auditory nerve fibers, a number of representation schemes have been suggested that extract the vowel’s formant frequencies from auditory nerve-fiber spiking patterns. The current study aims to apply and compare these schemes for auditory nerve-fiber responses to naturally-spoken vowels in a speech-shaped background noise. Responses to three vowels were evaluated; based on behavioral experiments in the same species, two of these were perceptually difficult to discriminate from each other (/e/vs/i/) and one was perceptually easy to discriminate from the other two (/a:/). Single-unit auditory nerve fibers were recorded from ketamine/xylazine-anesthetized Mongolian gerbils of either sex (n = 8). First, single-unit discrimination between the three vowels was studied. Compared to the perceptually easy discriminations, the average spike timing-based discrimination values were significantly lower for the perceptually difficult vowel discrimination. This was not true for an ...

Bodily rhythms appear as novel scaffolding mechanisms orchestrating the spatio-temporal organization of spontaneous brain activity. Here, we follow up on the discovery of the gastric resting-state network (Rebollo et al, 2018), composed of brain regions in which the fMRI signal is phase-synchronized to the slow (0.05 Hz) electrical rhythm of the stomach. Using a larger sample size (n=63 human participants, both genders), we further characterize the anatomy and effect sizes of gastric-brain coupling across resting-state networks, a fine grained cortical parcellation, as well as along the main gradients of cortical organization. Most (67%) of the gastric network is included in the somato-motor-auditory (38%) and visual (29%) resting state networks. Gastric brain coupling also occurs in the granular insula and, to a lesser extent, in the piriform cortex. Thus, all sensory and motor cortices corresponding to both exteroceptive and interoceptive modalities are coupled to the gastric rhythm during rest. Converse...

Electrical stimulation of the peripheral nerves of human participants provides a unique opportunity to study the neural determinants of perceptual quality using a causal manipulation. A major challenge in the study of neural coding of touch has been to isolate the role of spike timing – at the scale of milliseconds or tens of milliseconds – in shaping the sensory experience. In the present study, we address this question by systematically varying the frequency (PF) of electrical stimulation pulse trains delivered to the peripheral nerves of seven participants with upper and lower extremity limb loss via chronically implanted neural interfaces. We find that increases in PF lead to systematic increases in perceived frequency, up to about 50 Hz, at which point further changes in PF have little to no impact on sensory quality. Above this transition frequency, ratings of perceived frequency level off, the ability to discriminate changes in PF is abolished, and verbal descriptors selected to characterize the sen...

The dorsal raphe nucleus (DRN) contains the largest population of serotonin (5-HT) neurons in the central nervous system. 5-HT, synthesized via tryptophan hydroxylase 2 (Tph2), is a widely functioning neuromodulator implicated in fear learning. Here we sought to investigate whether DRN 5-HT is necessary to reduce fear via negative prediction error. Using male and female TPH2-cre rats, DRNtph2+ cells were selectively deleted via cre-caspase (rAAV5-Flex-taCasp3-TEVp) in Experiment 1. Rats then underwent fear discrimination during which three cues were associated with unique foot shock probabilities: safety p=0.00, uncertainty p=0.375, and danger p=1.00. Rats then received selective extinction to the uncertainty cue, a behavioral manipulation designed to probe negative prediction error. Deleting DRNtph2+ cells had no impact on initial discrimination but slowed selective extinction. In Experiment 2, we used a within-subjects optogenetic inhibition design to causally implicate DRNtph2+ cells in prediction error...

Efficient and reliable neurotransmission requires precise coupling between action potentials, Ca2+ entry and neurotransmitter release. However, Ca2+ requirements for release, including the number of channels required, their subtypes, and their location with respect to primed vesicles, remains to be precisely defined for central synapses. Indeed, Ca2+ entry may occur through small numbers or even single open Ca2+ channels, but these questions remain largely unexplored in simple active zone (AZ) synapses common in the nervous system, and key to addressing Ca2+ channel and synaptic dysfunction underlying numerous neurological and neuropsychiatric disorders. Here, we present single channel analysis of evoked AZ Ca2+ entry, using cell-attached patch clamp and lattice light-sheet microscopy, resolving small channel numbers evoking Ca2+ entry following depolarization, at single AZs in individual central lamprey reticulospinal presynaptic terminals from male and females. We show a small pool (mean of 23) of Ca2+ c...

Visual processing is strongly influenced by the recent stimulus history – a phenomenon termed adaptation. Prominent theories cast adaptation as a consequence of optimized encoding of visual information, by exploiting the temporal statistics of the world. However, this would require the visual system to track the history of individual briefly experienced events, within a stream of visual input, to build up statistical representations over longer timescales. Here, using an openly available dataset from the Allen Brain Observatory, we show that neurons in the early visual cortex of the mouse indeed maintain long-term traces of individual past stimuli that persist despite the presentation of several intervening stimuli, leading to long-term and stimulus-specific adaptation over dozens of seconds. Long-term adaptation was selectively expressed in cortical, but not in thalamic neurons, which only showed short-term adaptation. Early visual cortex thus maintains concurrent stimulus-specific memory traces of past i...

Collaboration in neuroscience is impeded by the difficulty of sharing primary data, results, and software across labs. Here we introduce Neuroscience Data Interface (NDI), a platform-independent standard that allows an analyst to use and create software that functions independently from the format of the raw data or the manner in which the data is organized into files. The interface is rooted in a simple vocabulary that describes common apparatus and storage devices used in neuroscience experiments. Results of analyses – and analyses of analyses – are stored as documents in a scalable, queryable database that stores the relationships and history among the experiment elements and documents. The interface allows the development of an application ecosystem where applications can focus on calculation rather than data format or organization. This tool can be used by individual labs to exchange and analyze data, and it can serve to curate neuroscience data for searchable archives. Significance Statement Neuro...