Bilateral convergence of external stimuli is a common feature of vertebrate sensory systems. This convergence of inputs from the bilateral receptive fields allows higher order sensory perception, such as depth perception in the vertebrate visual system and stimulus localization in the auditory system. The functional role of such bilateral convergence in the olfactory system is unknown. To test whether each olfactory bulb (OB) contributes a separate piece of olfactory information, and whether information from the bilateral OB is integrated, we synchronized the activation of OBs with blue light in mice expressing ChIEF in the olfactory sensory neurons (OSNs) and behaviorally assessed the relevance of dual OBs in olfactory perception. Our findings suggest that each OB contributes separate components of olfactory information, and the mice integrate the bilaterally synchronized olfactory information for olfactory identity.

Temperature-sensitive two-pore domain potassium channels (thermal K2P) are recently shown to cluster at nodes of Ranvier (NRs) and play a key role in action potential (AP) regeneration and conduction on Aβ-afferent nerves. Cooling temperatures affect AP regeneration and conduction on Aβ-afferent nerves but the underlying mechanisms are not completely understood. Here, we have performed patch-clamp recordings directly at the NR in an ex vivo trigeminal nerve preparation. We have characterized the effects of cooling temperatures on intrinsic electrophysiological properties and AP regeneration at the NR on rat Aβ-afferent nerves, and determined whether and how thermal K2P channels may be involved in the effects of cooling temperatures. We show that cooling temperatures from 35°C to 15°C decrease outward leak currents, increase input resistance, depolarize resting membrane potential (RMP), broaden AP width and increase latency of AP threshold at the NR. We further demonstrate that cooling temperatures impair r...

Striatal activity is necessary to initiate and execute sequences of actions. The main excitatory input to the striatum comes from the cortex. While it is hypothesized that motor and premotor cortico-striatal projections are important to guide striatal activity during the execution of sequences of actions, technical limitations have made this challenging to address. Here, we implemented a task in mice that allows for the study of different moments to execute a serial order sequence consisting of two subsequences of actions. Using this task, we performed electrophysiological recordings in the premotor (M2) and primary motor (M1) cortices, and state-dependent optogenetic inhibitions of their cortico-striatal projections. We show that while both M2 and M1 contain activity modulations related to the execution of self-paced sequences, mainly, the premotor cortico-striatal projections contribute to the proper execution/structuring of these sequences.

In the mature mouse retina, Otx2 is expressed in both retinal pigmented epithelium (RPE) and photoreceptor (PR) cells, and Otx2 knock-out (KO) in the RPE alone results in PR degeneration. To study the cell-autonomous function of OTX2 in PRs, we performed PR-specific Otx2 KO (cKO) in adults. As expected, the protein disappears completely from PR nuclei but is still observed in PR inner and outer segments while its level concomitantly decreases in the RPE, suggesting a transfer of OTX2 from RPE to PRs in response to Otx2 ablation in PRs. The ability of OTX2 to transfer from RPE to PRs was verified by viral expression of tagged-OTX2 in the RPE. Transferred OTX2 distributed across the PR cytoplasm, suggesting functions distinct from nuclear transcription regulation. PR-specific Otx2 cKO did not alter the structure of the retina but impaired the translocation of PR arrestin-1 on illumination changes, making mice photophobic. RNA-seq analyses following Otx2 KO revealed downregulation of genes involved in the cyt...

Mutations in the voltage-gated sodium channel gene SCN1A are associated with human epilepsy disorders, but how most of these mutations alter channel properties and result in seizures is unknown. This study focuses on two different mutations occurring at one position within SCN1A . R1648C (R-C) is associated with the severe disorder Dravet syndrome, and R1648H (R-H), with the milder disorder GEFS+. To explore how these different mutations contribute to distinct seizure disorders, Drosophila lines with the R-C or R-H mutation, or R1648R (R-R) control substitution in the fly sodium channel gene para were generated by CRISPR-Cas9 gene editing. The R-C and R-H mutations are homozygous lethal. Animals heterozygous for R-C or R-H mutations displayed reduced life spans and spontaneous and temperature-induced seizures not observed in R-R controls. Electrophysiological recordings from adult GABAergic neurons in R-C and R-H mutants revealed the appearance of sustained neuronal depolarizations and altered firing frequ...

Recent studies suggest that choice behavior in reinforcement learning tasks is shaped by the level of outcome controllability. In particular, Pavlovian bias (PB) seems to be enhanced under low levels of control, manifesting in approach tendencies toward rewards and response inhibition when facing potential losses. The medial prefrontal cortex (mPFC) has been implicated both in evaluating outcome controllability and in the recruitment of cognitive control (CC) to suppress maladaptive PB during reinforcement learning. The current study tested whether high-definition transcranial direct current stimulation (HD-tDCS) above the mPFC of healthy humans can influence PB, and counteract the previously documented, deleterious behavioral effects of low outcome controllability on decision-making. In a preregistered, between-group, double-blind study ( N  = 103 adults, both sexes), we tested the interaction between controllability and HD-tDCS on parameters of choice behavior in a Go/NoGo task. Relative to sham stimulat...

Molecular, anatomic, and behavioral studies show that the hippocampus is structurally and functionally heterogeneous, with dorsal hippocampus implicated in mnemonic processes and spatial navigation and ventral hippocampus involved in affective processes. By performing electrophysiological recordings of large neuronal populations in dorsal and ventral CA1 in head-fixed mice navigating a virtual environment, we found that this diversity resulted in different strategies for population coding of space. Populations of neurons in dorsal CA1 showed more complex patterns of activity, which resulted in a higher dimensionality of neural representations that translated to more information being encoded, as compared ensembles in vCA1. Furthermore, a pairwise maximum entropy model was better at predicting the structure of these global patterns of activity in ventral CA1 as compared with dorsal CA1. Taken together, the different coding strategies we uncovered likely emerge from anatomic and physiological differences alo...

The opioid epidemic led to an increase in the number of neonatal opioid withdrawal syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS. Neonatal outbred Swiss Webster Cartworth Farms White (CFW) mice were administered morphine (15 mg/kg, s.c.) twice daily from postnatal day 1 (P1) to P14, an approximation of the third trimester of human gestation. Female and male mice underwent behavioral testing on P7 and P14 to determine the impact of opioid exposure on anxiety and pain sensitivity. Ultrasonic vocalizations (USVs) and daily body weights were also recorded. Brainstems containing pons and medulla were collected during morphine withdrawal on P14 for RNA sequencing. Morphine induced weight loss from P2 to P14, which persisted during adolescence (P21) and adulthood (P50). USVs markedly increase...

Neurons are highly vulnerable to conditions of hypoxia-ischemia (HI) such as stroke or transient ischemic attacks. Recovery of cognitive and behavioral functions requires re-emergence of coordinated network activity, which, in turn, relies on the well-orchestrated interaction of pyramidal cells (PYRs) and interneurons. We therefore modelled HI in the mouse hippocampus, a particularly vulnerable region showing marked loss of PYR and fast-spiking interneurons (FSIs) after hypoxic-ischemic insults. Transient oxygen-glucose deprivation (OGD) in ex vivo hippocampal slices led to a rapid loss of neuronal activity and spontaneous network oscillations (sharp wave-ripple complexes; SPW-Rs), and to the occurrence of a spreading depolarization. Following reperfusion, both SPW-R and neuronal spiking resumed, but FSI activity remained strongly reduced compared with PYR. Whole-cell recordings in CA1 PYR revealed, however, a similar reduction of both EPSCs and IPSCs, leaving inhibition-excitation (I/E) balance unaltered....

Savings have been described as the ability of healthy humans to relearn a previously acquired motor skill faster than the first time, which in the context of motor adaptation suggests that the learning rate in the brain could be adjusted when a perturbation is recognized. Alternatively, it has been argued that apparent savings were the consequence of a distinct process that instead of reflecting a change in the learning rate, revealed an explicit re-aiming strategy. Based on recent evidence that feedback adaptation may be central to both planning and control, we hypothesized that this component could genuinely accelerate relearning in human adaptation to force fields (FFs) during reaching. Consistent with our hypothesis, we observed that on re-exposure to a previously learned FF, the very first movement performed by healthy volunteers in the relearning context was better adapted to the external disturbance, and this occurred without any anticipation or cognitive strategy because the relearning session was ...