The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g. cough, bronchospasm). Airway innervation is heterogeneous, and distinct afferent subsets have distinct functional responses. However, little is known of the innervation patterns of subsets within the lung. A neuroanatomical map is critical for understanding afferent activation under physiological and pathophysiological conditions. Here, we quantified the innervation of the mouse lung by vagal and dorsal root ganglion (DRG) sensory subsets defined by the expression of Pirt (all afferents), 5HT3 (vagal nodose afferents), Tac1 (tachykinergic afferents) and TRPV1 (defensive/nociceptive afferents) using Cre-mediated reporter expression. We found that vagal afferents innervate almost all conducting airways and project into the alveolar region, whereas DRG afferents only innervate large airways. Of the two vagal ganglia, only nodose afferents project into the alveolar region,...

Single-brain neuroimaging studies have shown that human cooperation is associated with neural activity in frontal and temporoparietal regions. However, it remains unclear whether single-brain studies are informative about cooperation in real life, where people interact dynamically. Such dynamic interactions have become the focus of inter-brain studies. An advantageous technique in this regard is functional near-infrared spectroscopy (fNIRS) because it is less susceptible to movement artifacts than more conventional techniques like EEG or fMRI. We conducted a systematic review and the first quantitative meta-analysis of fNIRS hyperscanning of cooperation, based on thirteen studies with 890 human participants. Overall, the meta-analysis revealed evidence of statistically significant inter-brain synchrony while people were cooperating, with large overall effect sizes in both frontal and temporoparietal areas. All thirteen studies observed significant inter-brain synchrony in the prefrontal cortex (PFC), sugge...

Motor cortical neurons exhibit persistent selective activities (selectivity) during motor planning. Experimental perturbation of selectivity results in the failure of short-term memory retention and consequent behavioral biases, demonstrating selectivity as a neural characteristic of encoding previous sensory input or future action. However, even without experimental manipulation, animals occasionally fail to maintain short-term memory leading to erroneous choice. Here, we investigated neural substrates that lead to the incorrect formation of selectivity during short-term memory. We analyzed neuronal activities in anterior lateral motor cortex (ALM) of mice, a region known to be engaged in motor planning while mice performed the tactile delayed-response task. We found that highly selective neurons lost their selectivity while originally non-selective neurons showed selectivity during the error trials where mice licked toward incorrect direction. We assumed that those alternations would reflect changes in i...

The limited ability for axonal repair after spinal cord injury underlies long-term functional impairment. DLK (MAP3K12) is an evolutionarily conserved MAP3K implicated in neuronal injury signaling from C. elegans to mammals. However, whether DLK or its close homologue LZK (MAP3K13) regulates axonal repair in the mammalian spinal cord remains unknown. Here we assess the role of endogenous DLK and LZK in the regeneration and compensatory sprouting of corticospinal tract (CST) axons in mice of both sexes with genetic analyses in a regeneration competent background provided by PTEN deletion. We found that inducible neuronal deletion of both DLK and LZK, but not either kinase alone, abolishes PTEN deletion-induced regeneration and sprouting of CST axons, and reduces naturally-occurring axon sprouting after injury. Thus, DLK/LZK-mediated injury signaling operates not only in injured neurons to regulate regeneration, but also unexpectedly in uninjured neurons to regulate sprouting. Deleting DLK and LZK does not i...

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context-sensitivity is caused by faster updating of one’s model of the world (i.e. higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. An autism and matched control group of human adults (both n =27, 8 female) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e. the standard and deviant sound in the first block) influences MMN ampl...

Sleep is a universally conserved physiological state which contributes towards basic organismal functions including cognitive operations such as learning and memory. Intriguingly, organisms can sometimes form memory even without sleep, such that Drosophila display sleep-dependent and sleep-independent memory in an olfactory appetitive training paradigm. Sleep-dependent memory can be elicited by the perception of sweet taste, and we now show that a mixed-sex population of flies maintained on sorbitol, a tasteless but nutritive substance, do not require sleep for memory consolidation. Consistent with this, silencing sugar-sensing gustatory receptor neurons (GRNs) in fed flies triggers a switch to sleep-independent memory consolidation, while activating sugar-sensing GRNs results in the formation of sleep-dependent memory in starved flies. Sleep-dependent and sleep-independent memory rely on distinct subsets of reward signaling protocerebral anterior medial dopaminergic neurons (PAM DANs) such that PAM-β’2mp ...

Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation, which has profound effects on neuronal processing, cognition, and behavior. However, little is known about the cortical control and effects of pupil-linked neuromodulation. Here, we show that pupil dynamics are tightly coupled to temporally, spectrally, and spatially specific modulations of local and large-scale cortical population activity in the human brain. We quantified the dynamics of band-limited cortical population activity in resting human subjects using magnetoencephalography (MEG) and investigated how neural dynamics were linked to simultaneously recorded pupil dynamics. Our results show that pupil-linked neuromodulation does not merely affect cortical population activity in a stereotypical fashion. Instead, we identified three frontal, precentral and occipitoparietal networks, in which local population activity with distinct spectral profiles in the theta, beta and alpha bands temporally prece...

The molecular mechanisms underlying somatodendritic dopamine (DA) release remain unresolved, despite the passing of decades since its discovery. Our previous work showed robust release of somatodendritic DA in submillimolar extracellular Ca2+ concentration ([Ca2+]o). Here we tested the hypothesis that the high-affinity Ca2+ sensor, synaptotagmin 7 (Syt7), is a key determinant of somatodendritic DA release and its Ca2+ dependence. Somatodendritic DA release from SNc DA neurons was assessed using whole-cell recording in midbrain slices from male and female mice to monitor evoked D2 DA autoreceptor-dependent inhibitory currents (D2ICs). Single-cell application of an antibody to Syt7 (Syt7 Ab) decreased pulse-train evoked D2ICs, revealing a functional role for Syt7. Assessment of the Ca2+-dependence of pulse-train evoked D2ICs confirmed robust DA release in submillimolar [Ca2+]o in wild-type (WT) neurons, but loss of this sensitivity with intracellular Syt7 Ab or in Syt7 knockout (KO) mice. In millimolar [Ca2+...

Calretinin (CR) is a major calcium binding protein widely expressed in the CNS. However, its synaptic function remains largely elusive. At the auditory synapse of the endbulb of Held, CR is selectively expressed in different subtypes. Combining electrophysiology with immunohistochemistry, we investigated the synaptic transmission at the endbulb of Held synapses with and without endogenous CR expression in mature CBA/CAJ mice of either sex. Two synapse subtypes showed similar basal synaptic transmission, except a larger quantal size in CR-expressing synapses. During high-rate stimulus trains, CR-expressing synapses showed improved synaptic efficacy with significantly less depression and lower asynchronous release, suggesting more efficient exocytosis than non-CR-expressing synapses. Conversely, CR-expressing synapses had a smaller readily releasable pool size, which was countered by higher release probability and faster synaptic recovery to support sustained release during high-rate activity. EGTA-AM treatm...