Retinal ganglion cells (RGCs) project topographically to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN). Spontaneous activity plays a critical role in retinotopic mapping in both regions; however, the molecular mechanisms underlying activity-dependent refinement remain unclear. Previous pharmacologic studies implicate NMDA receptors (NMDARs) in the establishment of retinotopy. In other brain regions, NMDARs are expressed on both the presynaptic and postsynaptic side of the synapse, and recent work suggests that presynaptic and postsynaptic NMDARs play distinct roles in retinotectal developmental dynamics. To directly test the role of NMDARs expressed by RGCs in retinofugal map formation, we took a conditional genetic knock-out approach to delete the obligate GluN1 subunit of NMDARs in RGCs. Here, we demonstrate reduced GluN1 expression in the retina of Chrnb3-Cre;GluN1flox/flox (pre-cKO) mice without altered expression in the SC. Anatomical tracing experiments revealed no signifi...

Cells in the entorhinal cortex (EC) contain rich spatial information and project strongly to the hippocampus where a cognitive map is supposedly created. These cells range from cells with structured spatial selectivity, such as grid cells in the medial EC (MEC) that are selective to an array of spatial locations that form a hexagonal grid, to weakly spatial cells, such as non-grid cells in the MEC and lateral EC (LEC) that contain spatial information but have no structured spatial selectivity. However, in a small environment, place cells in the hippocampus are generally selective to a single location of the environment, while granule cells in the dentate gyrus of the hippocampus have multiple discrete firing locations but lack spatial periodicity. Given the anatomic connection from the EC to the hippocampus, how the hippocampus retrieves information from upstream EC remains unclear. Here, we propose a unified learning model that can describe the spatial tuning properties of both hippocampal place cells and...

Nitrous oxide (N2O) is a hypnotic gas with antidepressant and psychedelic properties at subanesthetic concentrations. Despite long-standing clinical use, there is insufficient understanding of its effect on neural dynamics and cortical processing, which is important for mechanistic understanding of its therapeutic effects. We administered subanesthetic (70%), inhaled N2O and studied the dynamic changes of spiking rate, spectral content, and somatosensory information representation in primary motor cortex (M1) in two male rhesus macaques implanted with Utah microelectrode arrays in the hand area of M1. The average sorted multiunit spiking rate in M1 increased from 8.1 ± 0.99 to 10.6 ± 1.3 Hz in Monkey W ( p  <   0.001) and from 5.6 ± 0.87 to 7.0 ± 1.1 Hz in Monkey N ( p  =   0.003). Power spectral densities increased in beta- and gamma-band power. To evaluate somatosensory content in M1 as a surrogate of information transfer, fingers were lightly brushed and classified using a naive Bayes classifier. In bot...

Gonadotropin-releasing hormone (GnRH) drives pituitary secretion of luteinizing hormone and follicle-stimulating hormone, which in turn regulate gonadal functions including steroidogenesis. The pattern of GnRH release and thus fertility depend on gonadal steroid feedback. Under homeostatic (negative) feedback conditions, removal of the gonads from either females or males increases the amplitude and frequency of GnRH release and alters the long-term firing pattern of these neurons in brain slices. The neurobiological mechanisms intrinsic to GnRH neurons that are altered by homeostatic feedback are not well studied and have not been compared between sexes. During estradiol-positive feedback, which is unique to females, there are correlated changes in voltage-gated potassium currents and neuronal excitability. We thus hypothesized that these same mechanisms would be engaged in homeostatic negative feedback. Voltage-gated potassium channels play a direct role in setting excitability and action potential proper...

Listening to vocal music has been recently shown to improve language recovery in stroke survivors. The neuroplasticity mechanisms supporting this effect are, however, still unknown. Using data from a three-arm, single-blind, randomized controlled trial including acute stroke patients ( N  = 38) and a 3 month follow-up, we set out to compare the neuroplasticity effects of daily listening to self-selected vocal music, instrumental music, and audiobooks on both brain activity and structural connectivity of the language network. Using deterministic tractography, we show that the 3 month intervention induced an enhancement of the microstructural properties of the left frontal aslant tract (FAT) for the vocal music group compared with the audiobook group. Importantly, this increase in the strength of the structural connectivity of the left FAT correlated with improved language skills. Analyses of stimulus-specific activation changes showed that the vocal music group exhibited increased activations in the frontal...

The adaptable transcriptional response to changes in food availability not only ensures animal survival, but also lets progressing with embryonic development. Interestingly, the central nervous system is preferentially protected to periods of malnutrition, a phenomenon known as ‘ brain sparing ’. However, the mechanisms that mediates this response remains poorly understood. To get a better understanding of this, we used Drosophila melanogaster as a model, analysing the transcriptional response of neural stem cells (neuroblasts) and glia of the blood-brain barrier (BBB), from larvae of both sexes, during nutrient restriction using targeted DamID. We found differentially expressed genes in both neuroblasts and glia of the BBB, although the effect of nutrient deficiency was primarily observed in the BBB. We characterised the function of a nutritional sensitive gene expressed in the BBB, the serine protease homologue, scarface ( scaf ). Scaf is expressed in subperineurial glia in the BBB in response to nutriti...

Textbook descriptions of primary sensory cortex (PSC) revolve around single neurons’ representation of low-dimensional sensory features, such as visual object orientation in V1, location of somatic touch in S1, and sound frequency in A1. Typically, studies of PSC measure neurons’ responses along few (1 or 2) stimulus and/or behavioral dimensions. However, real-world stimuli usually vary along many feature dimensions and behavioral demands change constantly. In order to illuminate how A1 supports flexible perception in rich acoustic environments, we recorded from A1 neurons while rhesus macaques (one male, one female) performed a feature-selective attention task. We presented sounds that varied along spectral and temporal feature dimensions (carrier bandwidth and temporal envelope, respectively). Within a block, subjects attended to one feature of the sound in a selective change detection task. We found that single neurons tend to be high-dimensional, in that they exhibit substantial mixed selectivity for b...

The orbitofrontal cortex (OFC) and hippocampus share striking cognitive and functional similarities. As a result, both structures have been proposed to encode “cognitive maps” that provide useful scaffolds for planning complex behaviors. However while this function has been exemplified by spatial coding in neurons of hippocampal regions—particularly place and grid cells—spatial representations in the OFC have been investigated far less. Here we sought to address this by recording OFC neurons from male rats engaged in an open-field foraging task like that originally developed to characterize place fields in rodent hippocampal neurons. Single unit activity was recorded as rats searched for food pellets scattered randomly throughout a large enclosure. In some sessions, particular flavors of food occurred more frequently in particular parts of the enclosure; in others, only a single flavor was used. OFC neurons showed spatially-localized firing fields in both conditions, and representations changed between fla...

Human listeners achieve quick and effortless speech comprehension through computations of conditional probability using Bayes rule. However, the neural implementation of Bayesian perceptual inference remains unclear. Competitive-selection accounts (e.g. TRACE) propose that word recognition is achieved through direct inhibitory connections between units representing candidate words that share segments (e.g. hygiene and hijack share/haidʒ/). Manipulations that increase lexical uncertainty should increase neural responses associated with word recognition when words cannot be uniquely identified. In contrast, predictive-selection accounts (e.g. Predictive-Coding) proposes that spoken word recognition involves comparing heard and predicted speech sounds and using prediction error to update lexical representations. Increased lexical uncertainty in words like hygiene and hijack will increase prediction error and hence neural activity only at later time points when different segments are predicted. We collected ME...

Sonic Hedgehog (Shh) signaling from the primary cilium drives cerebellar granule cell precursor (GCP) proliferation. Mutations of hedgehog (Hh) pathway repressors commonly cause medulloblastoma, the most prevalent and malignant childhood brain tumor that arises from aberrant GCP proliferation. We demonstrate that Nestin Cre-driven conditional knockout of a Shh pathway repressor- Rab23 in the mouse brain of both genders caused mis-patterning of cerebellar folia and elevated GCP proliferation during early development, but with no prevalent occurrence of medulloblastoma at adult stage. Strikingly, Rab23- depleted GCPs exhibited up-regulated basal level of Shh pathway activities despite showing an abnormal ciliogenesis of primary cilia. In line with the compromised ciliation, Rab23- depleted GCPs were desensitized against Hh pathway activity stimulations by Shh ligand and Smoothened (Smo) agonist-SAG, and exhibited attenuated stimulation of Smo-localization on the primary cilium in response to SAG. These resul...