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-...

Neuronal ensembles are groups of neurons with coordinated activity that could represent sensory, motor, or cognitive states. The study of how neuronal ensembles are built, recalled, and involved in the guiding of complex behaviors has been limited by the lack of experimental and analytical tools to reliably identify and manipulate neurons that have the ability to activate entire ensembles. Such “pattern completion” neurons have also been proposed as key elements of artificial and biological neural networks. Indeed, the relevance of pattern completion is highlighted by growing evidence that targeting them can activate neuronal ensembles and trigger behavior. As a method to reliably detect pattern completion neurons, we use Conditional Random Fields (CRFs), a type of probabilistic graphical models. We apply CRFs to identify pattern completion neurons in ensembles in experiments using in vivo two-photon calcium imaging from primary visual cortex of male mice and confirm the CRFs predictions with two-photon op...

Decision-making not only requires agents to decide what to choose, but also how much information to sample before committing to a choice. Previously established frameworks for economic choice argue for a deliberative process of evidence accumulation across time. These tacitly acknowledge a role of information sampling, in that decisions are only made once sufficient evidence is acquired, yet few experiments have explicitly placed information sampling under the participant’s control. Here, we use functional MRI to investigate the neural basis of information sampling in economic choice, by allowing participants (n=30, sex not recorded) to actively sample information in a multi-step decision task. We show that medial frontal cortex (MFC) activity is predictive of further information sampling prior to choice. Choice difficulty (inverse value difference, keeping sensory difficulty constant) was also encoded in MFC, but this effect was explained away by the inclusion of information sampling as a co-regressor in ...

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...

Different types of tissue injury, such as inflammatory and neuropathic conditions, cause modality specific alternations on temperature perception. There are profound changes in peripheral sensory neurons after injury, but how patterned neuronal activities in the central nervous system encode injury-induced sensitization to temperature stimuli is largely unknown. Using in vivo calcium imaging and mouse genetics, we show that formalin- and prostaglandin E2-induced inflammation dramatically increase spinal responses to heating and decrease responses to cooling in male and female mice. The reduction of cold response is largely eliminated upon ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from the hyperactive heat inputs in the spinal cord. Interestingly, chemotherapy medication oxaliplatin can rapidly increase spinal responses to cooling and suppress responses to heating. Together, our results suggest a push/pull mechanism in processing cold and heat i...

JNeurosci is publishing an Expression of Concern for the article, “Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17,” by Javier Palazuelos, Michael Klingener, Elaine W. Raines, Howard C. Crawford, and Adan Aguirre, which appeared on pages [12241–12247][1] of the September