Select neuronal populations display steady rhythmic neuronal firing that provides tonic excitation to drive downstream networks and behaviors. In noradrenergic neurons of the locus coeruleus (LC), circadian neurons of the suprachiasmatic nucleus (SCN), and CO2/H+-activated neurons of the brainstem retrotrapezoid nucleus (RTN), large subthreshold membrane potential oscillations contribute to the pacemaker-like action potential discharge. The oscillations and firing in LC and SCN involve contributions from leak sodium (NALCN) and L-type calcium channels while recent work from RTN suggested an additional pivotal role for a secondary calcium-activated and voltage-gated cationic current carried by TRPM4. Here, we tested whether TRPM4 contributes to subthreshold oscillations in mouse LC and SCN. By RNAscope in situ hybridization, Trpm4 transcripts were detected in both cell groups. In whole cell recordings from acute slice preparations, prominent voltage-dependent membrane potential oscillations were revealed in...

Neurons in the developing visual cortex undergo progressive functional maturation as indicated by the refinement of their visual feature selectivity. However, changes of the synaptic architecture underlying the maturation of spatial visual receptive fields (RFs) per se remain largely unclear. Here, loose-patch as well as single-unit recordings in layer 4 of mouse primary visual cortex (V1) of both sexes revealed that RF development in a post-eye-opening period is marked by an increased proportion of cortical neurons with spatially defined RFs, together with the increased signal-to-noise ratio (SNR) of spiking responses. By exploring excitatory and inhibitory synaptic RFs with whole-cell voltage clamp recordings, we observed a balanced enhancement of both synaptic excitation and inhibition, and that while the excitatory subfield size remains relatively constant during development, the inhibitory subfield is broadened. This balanced developmental strengthening of excitatory and inhibitory synaptic inputs res...

Bilateral cochlear implants (BI-CIs) or a CI for single-sided deafness (SSD; one normally functioning acoustic ear) can partially restore spatial-hearing abilities, including sound localization and speech understanding in noise. For these populations, however, interaural place-of-stimulation mismatch can occur and thus diminish binaural sensitivity that relies on interaurally frequency-matched neurons. This study examined whether plasticity—reorganization of central neural pathways over time—can compensate for peripheral interaural place mismatch. We hypothesized differential plasticity across two systems: none for binaural processing but adaptation toward frequencies delivered by the specific electrodes for pitch perception. Interaural place mismatch was evaluated in 19 BI-CI and 23 SSD-CI human subjects (both sexes) using binaural processing (interaural-time-difference discrimination with simultaneous bilateral stimulation), pitch perception (pitch ranking for single electrodes or acoustic tones with seq...

Oligodendrocytes are vulnerable to genetic and environmental insults and its injury leads to demyelinating diseases. The roles of ErbB receptors in maintaining the CNS myelin integrity are largely unknown. Here we overactivate ErbB receptors that mediate signaling of either neuregulin or EGF family growth factors and found their synergistic activation caused deleterious outcomes in white matter. Sustained ErbB activation induced by the tetracycline-dependent mouse tool Plp -tTA resulted in demyelination, axonal degeneration, oligodendrocyte precursor cell (OPC) proliferation, astrogliosis, and microgliosis in white matter. Moreover, there was hypermyelination prior to these inflammatory pathological events. In contrast, sustained ErbB activation induced by another tetracycline-dependent mouse tool Sox10 +/rtTA caused hypomyelination in the corpus callosum and optic nerve, which appeared to be a developmental deficit and did not associate with OPC regeneration, astrogliosis, or microgliosis. By tracing the ...

Postsynaptic responses depend on input patterns as well as short-term synaptic plasticity, summation, and postsynaptic membrane properties, but the interactions of those dynamics with realistic input patterns are not well understood. We recorded the responses of the two pyloric dilator (PD) muscles, cpv2a and cpv2b , that are innervated by and receive identical periodic bursting input from the same two motor neurons in the lobster Homarus americanus . Cpv2a and cpv2b showed quantitative differences in membrane nonlinearities and synaptic summation. At a short timescale, responses in both muscles were dominated by facilitation, albeit with different frequency and time dependence. Realistic burst stimulations revealed more substantial differences. Across bursts, cpv2a showed transient depression, whereas cpv2b showed transient facilitation. Steady-state responses to bursting input also differed substantially. Neither muscle had a monotonic dependence on frequency, but cpv2b showed particularly pronounced ban...

Auditory stimuli travel from the cochlea to the brainstem through type I and type II cochlear afferents. While type I afferents convey information about the frequency, intensity, and timing of sounds, the role of type II afferents remains unresolved. Limited recordings of type II afferents from cochlear apex of prehearing rats reveal they are activated by widespread outer hair cell stimulation, ATP, and by the rupture of nearby outer hair cells. Altogether, these lines of evidence suggest that type II afferents sense loud, potentially damaging levels of sound. To explore this hypothesis further, calcium imaging was used to determine the impact of acoustic trauma on the activity of type II cochlear afferents of young adult mice of both sexes. Two known marker genes ( Th , Drd2 ) and one new marker gene ( Tac1 ), expressed in type II afferents and some other cochlear cell types, drove GCaMP6f expression to reveal calcium transients in response to focal damage in the organ of Corti in all turns of the cochlea...

Human heading perception from optic flow is accurate for directions close to the straight-ahead and systematic biases emerge in the periphery ([Cuturi and Macneilage, 2013][1]; [Sun et al., 2020][2]). In pursuit of the underlying neural mechanisms, primate brain dorsal medial superior temporal (MSTd) area has been a focus because of its causal link with heading perception ([Gu et al., 2012][3]). Computational models generally explain heading sensitivity in individual MSTd neurons as a feedforward integration of motion signals from medial temporal (MT) area that resemble full-field optic flow patterns consistent with the preferred heading direction ([Britten, 2008][4]; [Mineault et al., 2012][5]). In the present simulation study, we quantified within the structure of this feedforward model how physiological properties of MT and MSTd shape heading signals. We found that known physiological tuning characteristics generally supported the accuracy of heading estimation, but not always. A weak-to-moderate overre...

For proper execution of goal-directed behaviors, individuals require both a general representation of the goal and an ability to monitor their own progress toward that goal. Here, we examine how dorsomedial striatum (DMS), a region pivotal for forming associations among stimuli, actions, and outcomes, encodes the execution of goal-directed action sequences that require self-monitoring of behavior. We trained rats to complete a sequence of at least five consecutive lever presses (without visiting the reward port) to obtain a reward and recorded the activity of individual cells in DMS while rats performed the task. We found that the pattern of DMS activity gradually changed during the execution of the sequence, permitting accurate decoding of sequence progress from neural activity at a population level. Moreover, this sequence-related activity was blunted on trials where rats did not complete a sufficient number of presses. Overall, these data suggest a link between DMS activity and the execution of behavior...

Tracking and quantifying the abundance and location of cells in the developing brain is essential in neuroscience research, enabling a greater understanding of mechanisms underlying nervous system morphogenesis. Widely used experimental methods to quantify cells labeled with fluorescent markers, such as immunohistochemistry (IHC), in situ hybridization, and expression of transgenes via stable lines or transient in utero electroporations (IUEs), depend on accurate and consistent quantification of images. Current methods to quantify fluorescently-labeled cells rely on labor-intensive manual counting approaches, such as the Fiji plugin Cell Counter , which requires custom macros to enable higher-throughput analyses. Here, we present RapID Cell Counter, a semi-automated cell-counting tool with an easy-to-implement graphical user interface (GUI), which facilitates quick and consistent quantifications of cell density within user-defined boundaries that can be divided into equally-partitioned segments. Compared w...

Forced swim test (FST) and tail suspension test (TST) are commonly used behavioral tests for screening antidepressant drugs with a high predictive validity. These tests have also proved useful to assess the non-motor symptoms in the animal models of movement disorders such as Parkinson’s disease and Huntington’s disease. Manual analysis of FST and TST is a time-consuming exercise and has large observer-to-observer variability. Automation of behavioral analysis alleviates these concerns, but there are no easy-to-use open-source tools for such analysis. Here, we describe the development of Depression Behavior Scorer (DBscorer), an open-source program installable on Windows, with an intuitive graphical user interface (GUI), that helps in accurate quantification of immobility behavior in FST and TST from video analysis. Several calibration options allow customization of various parameters to suit the experimental requirements. Apart from the readout of time spent immobile, DBscorer also provides additional dat...