The middle temporal (MT) area of the extrastriate visual cortex has long been studied in adulthood for its distinctive physiological properties and function as a part of the dorsal stream, yet interestingly possesses a similar maturation profile as the primary visual cortex (V1). Here we examined whether an early-life lesion to MT of marmoset monkeys (6 female & 2 male) altered the dorsal stream development and the behavioral precision of reaching to grasp sequences. We observed permanent changes in the anatomy of cortices associated with both reaching (PE and MIP) and grasping (AIP), as well as in reaching and grasping behaviors. In addition, we observed a significant impact on the anatomy of V1 and the direction sensitivity of V1 neurons in the lesion projection zone. These findings indicate that area MT is a crucial node in the development of primate vision, impacting both V1 and areas in the dorsal visual pathway known to mediate visually guided manual behaviors. Significance Statement: Previous stu...

High molecular weight hyaluronan (HMWH), a well-established treatment for osteoarthritis pain, is anti-hyperalgesic in preclinical models of inflammatory and neuropathic pain. HMWH-induced anti-hyperalgesia is mediated by its action at cluster of differentiation 44 (CD44), the cognate hyaluronan receptor, which can signal via phosphoinositide 3-kinase (PI3K), a large family of kinases involved in diverse cell functions. We demonstrate that intrathecal administration of an oligodeoxynucleotide (ODN) antisense to mRNA for PI3Kγ (a class I PI3K isoform) expressed in dorsal root ganglia (DRG), and intradermal administration of a PI3Kγ selective inhibitor (AS605240), markedly attenuates HMWH-induced anti-prostaglandin E2 (PGE2) hyperalgesia, in male and female rats. Intradermal administration of inhibitors of mTOR (Rapamycin) and Protein Kinase B (AKT; AKT inhibitor IV), signaling molecules downstream of PI3Kγ, also attenuates HMWH-induced anti-hyperalgesia. In vitro patch-clamp electrophysiology experiments on...

Opsin 3 ( Opn3 ) is highly expressed in the adult brain, however, information for spatial and temporal expression patterns during embryogenesis is significantly lacking. Here an Opn3 -eGFP reporter mouse line was utilized to monitor cell body expression and axonal projections during embryonic and early postnatal to adult stages. By applying 2D and 3D fluorescence imaging techniques, we have identified the onset of Opn3 expression, which predominantly occurred during embryonic stages, in various structures during brain/head development. In addition, this study defines over twenty Opn3 -eGFP positive neural structures never reported before. Opn3 -eGFP was first observed at E9.5 in neural regions, including the ganglia that will ultimately form the trigeminal, facial and vestibulocochlear cranial nerves. As development proceeds, expanded Opn3 -eGFP expression coincided with the formation and maturation of critical components of the central and peripheral nervous systems, including various motor-sensory tracts...

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-...

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...