The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of the midbrain and pons, playing an important role in modulating posture and locomotion. Deep brain stimulation of the PPN has been proposed as an emerging treatment for patients with Parkinson’s disease (PD) or multiple system atrophy (MSA) suffering gait-related atypical parkinsonian syndromes. In this study, we investigated PPN activities during gait to better understand its functional role in locomotion. Specifically, we investigated whether PPN activity is rhythmically modulated by gait cycles during locomotion. PPN local field potential (LFP) activities were recorded from PD or MSA patients suffering from gait difficulties during stepping in place or free walking. Simultaneous measurements from force plates or accelerometers were used to determine the phase within each gait cycle at each time point. Our results showed that activities in the alpha and beta frequency bands in the PPN LFPs were rhythmically modulate...

Spinal cord injury (SCI) results in the development of detrimental autoantibodies against the lesioned spinal cord. IgM immunoglobulin maintains homeostasis against IgG-autoantibody responses, but its effect on SCI recovery remains unknown. In the present study we investigated the role of IgM immunoglobulin in influencing recovery after SCI. To this end, we induced cervical SCI at the C6/C7 level in mice that lacked secreted IgM immunoglobulin (IgM-KO) and their wild type (WT) littermate controls. Overall, the absence of secretory IgM resulted in worse outcomes as compared to WT mice with SCI. At two weeks post injury, IgM knock-out (KO) mice had significantly more IgG antibodies, which fixed the complement system, in the injured spinal cord parenchyma. In addition to these findings, IgM-KO mice had more parenchymal T-lymphocytes as well as CD11b+ microglia/macrophages, which co-localized with myelin. At 10 weeks post-injury, IgM-KO mice showed significant impairment in neurobehavioral recovery, such as de...

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 if each olfactory bulb contributes a separate piece of olfactory information, and if information from the bilateral olfactory bulb is integrated, we synchronized the activation of olfactory bulbs with blue light in mice expressing ChIEF in the olfactory sensory neurons and behaviorally assessed the relevance of dual olfactory bulbs in olfactory perception. Our findings suggest that each olfactory bulb contributes separate components of olfactory information, and the mice integrate the bilaterally synchronized olfactory information for olfactory identity. Significance statement Identifying an odor is the first step...

Neuroscience has been transformed by the ability to genetically modify inbred mice, including the ability to express fluorescent markers specific to cell types or activation states. This approach has been put to particularly good effect in the study of the innate immune cells of the brain, microglia. These specialized macrophages are exceedingly small and complex, but also highly motile and mobile. To-date, there have been no tools similar to those in mice available for studying these fundamental cells in the rat brain and we seek to fill that gap with the generation of the genetically modified Sprague-Dawley rat line: SD-Tg(Iba1-EGFP)Mmmc. Using CRISPR-Cas/9 technology, we knocked in EGFP to the promoter of the gene Iba1 . With 4 male and 3 female founders confirmed by qPCR analysis to have appropriate and specific insertion, we established a breeding colony with at least 3 generations of backcrosses to obtain stable and reliable Iba1-EGFP expression. Specificity of EGFP expression to microglia was establ...

Binocular disparity provides critical information about three-dimensional (3D) structure to support perception and action. The past decade has seen significant progress in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high field (7T) functional imagining at sub-millimetre resolution to examine fine-scale BOLD-fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We test for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception (i.e., correlated random dot stereograms: RDS) vs. those that do not (i.e., anti-correlated RDS). Using multi-voxel pattern analysis (MVPA...

Cue-induced cocaine craving progressively intensifies (incubates) after withdrawal from cocaine self-administration in rats and humans. In rats, the expression of incubation ultimately depends on Ca2+-permeable AMPARs (CP-AMPARs) that accumulate in synapses onto medium spiny neurons (MSN) in the nucleus accumbens (NAc) core. However, the delay in their accumulation (approximately 1 month after drug self-administration ceases) suggests earlier waves of plasticity. This prompted us to conduct the first study of NMDAR transmission in NAc core during incubation, focusing on the GluN3 subunit, which confers atypical properties when incorporated into NMDARs including insensitivity to Mg2+ block and Ca2+-impermeability. Whole-cell patch-clamp recordings were conducted in MSNs of adult male rats 1-68 days after discontinuing extended-access saline or cocaine self-administration. NMDAR transmission was enhanced after 5 days of cocaine withdrawal and this persisted for at least 68 days of withdrawal. The earliest fu...

When encoding new episodic memories, visual and semantic processing are proposed to make distinct contributions to accurate memory and memory distortions. Here, we used functional magnetic resonance imaging (fMRI) and preregistered representational similarity analysis (RSA) to uncover the representations that predict true and false recognition of unfamiliar objects. Two semantic models captured coarse-grained taxonomic categories and specific object features, respectively, while two perceptual models embodied low-level visual properties. Twenty-eight female and male participants encoded images of objects during fMRI scanning, and later had to discriminate studied objects from similar lures and novel objects in a recognition memory test. Both perceptual and semantic models predicted true memory. When studied objects were later identified correctly, neural patterns corresponded to low-level visual representations of these object images in the early visual cortex, lingual, and fusiform gyri. In a similar fash...

Experience-dependent formation and removal of synapses are essential throughout life. For instance, GABAergic synapses are removed to facilitate learning, and strong excitatory activity is accompanied by formation of inhibitory synapses to maintain coordination between excitation and inhibition. We recently discovered that active dendrites trigger the growth of inhibitory synapses via CB1 receptor-mediated endocannabinoid signaling, but the underlying mechanism remained unclear. Using two-photon microscopy to monitor the formation of individual inhibitory boutons in hippocampal organotypic slices from mice (both sexes), we found that CB1 receptor activation mediated the formation of inhibitory boutons and promoted their subsequent stabilization. Inhibitory bouton formation did not require neuronal activity and was independent of Gi/o protein signaling, but was directly induced by elevating cAMP levels using forskolin and by activating Gs proteins using DREADDs. Blocking PKA activity prevented CB1 receptor-...

The structural plasticity of dendritic spines is considered to be an important basis of synaptic plasticity, learning, and memory. Here, we induced input-specific structural LTP (sLTP) in single dendritic spines in organotypic hippocampal slices from mice of either sex and performed ultrastructural analyses of the spines using efficient correlative light and electron microscopy. We observed reorganization of the PSD nanostructure, such as perforation and segmentation, at 2–3, 20, and 120 min after sLTP induction. In addition, PSD and nonsynaptic axon–spine interface (nsASI) membrane expanded unevenly during sLTP. Specifically, the PSD area showed a transient increase at 2–3 min after sLTP induction. The PSD growth was to a degree less than spine volume growth at 2–3 min and 20 min after sLTP induction but became similar at 120 min. On the other hand, the nsASI area showed a profound and lasting expansion, to a degree similar to spine volume growth throughout the process. These rapid ultrastructural changes...

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at five different time points in 26 sighted female adults during 8 months of training on tactile braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occurring after braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after the cessation of learning in line with the supply–demand model of plasticity. These results also...