During neuronal migration, forces generated by cytoplasmic dynein yank on microtubules extending from the centrosome into the leading process and move the nucleus along microtubules that extend behind the centrosome. Scaffolds, such as radial glia, guide neuronal migration outward from the ventricles, but little is known about the internal machinery that ensures that the soma migrates along its proper path rather than moving backward or off the path. Here we report that depletion of KIFC1, a minus-end-directed kinesin called HSET in humans, causes neurons to migrate off their appropriate path, suggesting that this molecular motor is what ensures fidelity of the trajectory of migration. For these studies, we used rat migratory neurons in vitro and developing mouse brain in vivo , together with RNA interference and ectopic expression of mutant forms of KIFC1. We found that crosslinking of microtubules into a nonsliding mode by KIFC1 is necessary for dynein-driven forces to achieve sufficient traction to thru...

The high sensitivity of night vision requires that rod photoreceptors reliably and reproducibly signal the absorption of single photons, a process that depends on tight regulation of intracellular cGMP concentration through the phototransduction cascade. Here in the mouse (Mus musculus), we studied a single-site D167A mutation of the gene for the α subunit of rod photoreceptor phosphodiesterase (PDEA), made with the aim of removing a noncatalytic binding site for cGMP. This mutation unexpectedly eliminated nearly all PDEA expression and reduced expression of the β subunit (PDEB) to ∼5%-10% of WT. The remaining PDE had nearly normal specific activity; degeneration was slow, with 50%-60% of rods remaining after 6 months. Responses were larger and more sensitive than normal but slower in rise and decay, probably from slower dark turnover of cGMP. Remarkably, responses became much less reproducible than WT, with response variance increasing for amplitude by over 10-fold, and for latency and time-to-peak by >10...

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeA neurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeA neurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeA neurons directly projected to...

During multisensory speech perception, slow δ oscillations (∼1–3 Hz) in the listener's brain synchronize with the speech signal, likely engaging in speech signal decomposition. Notable fluctuations in the speech amplitude envelope, resounding speaker prosody, temporally align with articulatory and body gestures and both provide complementary sensations that temporally structure speech. Further, δ oscillations in the left motor cortex seem to align with speech and musical beats, suggesting their possible role in the temporal structuring of (quasi)-rhythmic stimulation. We extended the role of δ oscillations to audiovisual asynchrony detection as a test case of the temporal analysis of multisensory prosody fluctuations in speech. We recorded Electroencephalograph (EEG) responses in an audiovisual asynchrony detection task while participants watched videos of a speaker. We filtered the speech signal to remove verbal content and examined how visual and auditory prosodic features temporally (mis-)align. Results...

From an associative perspective the acquisition of new goal-directed actions requires the encoding of specific action-outcome (AO) associations and, therefore, sensitivity to the validity of an action as a predictor of a specific outcome relative to other events. Although competitive architectures have been proposed within associative learning theory to achieve this kind of identity-based selection, whether and how these architectures are implemented by the brain is still a matter of conjecture. To investigate this issue, we trained human participants to encode various AO associations while undergoing functional neuroimaging (fMRI). We then degraded one AO contingency by increasing the probability of the outcome in the absence of its associated action while keeping other AO contingencies intact. We found that this treatment selectively reduced performance of the degraded action. Furthermore, when a signal predicted the unpaired outcome, performance of the action was restored, suggesting that the degradatio...

The mouse primary visual cortex is a model system for understanding the relationship between cortical structure, function, and behavior (Seabrook et al., 2017; Chaplin and Margrie, 2020; Hooks and Chen, 2020; Saleem, 2020; Flossmann and Rochefort, 2021). Binocular neurons in V1 are the cellular basis of binocular vision, which is required for predation (Scholl et al., 2013; Hoy et al., 2016; La Chioma et al., 2020; Berson, 2021; Johnson et al., 2021). The normal development of binocular responses, however, has not been systematically measured. Here, we measure tuning properties of neurons to either eye in awake mice of either sex from eye opening to the closure of the critical period. At eye opening, we find an adult-like fraction of neurons responding to the contralateral-eye stimulation, which are selective for orientation and spatial frequency; few neurons respond to ipsilateral eye, and their tuning is immature. Fraction of ipsilateral-eye responses increases rapidly in the first few days after eye ope...

Higher vertebrates are capable not only of forward but also backward and sideways locomotion. Also, single steps in different directions are generated for postural corrections. While the networks responsible for the control of forward walking (FW) have been studied in considerable detail, the networks controlling steps in other directions are mostly unknown. Here, to characterize operation of the spinal locomotor network during FW and backward walking (BW), we recorded the activity of individual spinal interneurons from L4-L6 during both FW and BW evoked by epidural stimulation (ES) of the spinal cord at L5-L6 in decerebrate cats of either sex. Three groups of neurons were revealed. Group 1 (45%) had a similar phase of modulation during both FW and BW. Group 2 (27%) changed the phase of modulation in the locomotor cycle depending on the direction of locomotion. Group 3 neurons were modulated during FW only ( Group 3a , 21%) or during BW only ( Group 3b , 7%). We suggest that Group 1 neurons belong to the n...

Running direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored, and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2, and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a preferred firing rate direction of a place field, spikes are more likely to undergo theta phase precession and, hence, more strongly affect paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effec...

Most perceptual decisions rely on the active acquisition of evidence from the environment involving stimulation from multiple senses. However, our understanding of the neural mechanisms underlying this process is limited. Crucially, it remains elusive how different sensory representations interact in the formation of perceptual decisions. To answer these questions, we used an active sensing paradigm coupled with neuroimaging, multivariate analysis, and computational modeling to probe how the human brain processes multisensory information to make perceptual judgments. Participants of both sexes actively sensed to discriminate two texture stimuli using visual (V) or haptic (H) information or the two sensory cues together (VH). Crucially, information acquisition was under the participants' control, who could choose where to sample information from and for how long on each trial. To understand the neural underpinnings of this process, we first characterized where and when active sensory experience (movement pa...

Consistent with current models of embodied emotions, this study investigates whether the somatosensory system shows reduced sensitivity to facial emotional expressions in autistic compared with neurotypical individuals, and whether these differences are independent from between-group differences in visual processing of facial stimuli. To investigate the dynamics of somatosensory activity over and above visual carryover effects, we recorded EEG activity from two groups of autism spectrum disorder (ASD) or typically developing (TD) humans (male and female), while they were performing a facial emotion discrimination task and a control gender task. To probe the state of the somatosensory system during face processing, in 50% of trials we evoked somatosensory activity by delivering task-irrelevant tactile taps on participants' index finger, 105 ms after visual stimulus onset. Importantly, we isolated somatosensory from concurrent visual activity by subtracting visual responses from activity evoked by somatosens...