Journal of Neuroscience最新文献

Hedonic hotspots are localized brain sites where appropriate stimulations can amplify the hedonic impact of palatable tastes, measured as increases in affective orofacial 'liking' reactions to sweetness in rodents. Previously, two cortical hedonic hotspots in orbitofrontal cortex and insula were identified using opioid or orexin microinjections as neurochemical manipulations. Here we used optogenetic stimulation in male and female rats to independently confirm the sites and boundaries of two cortical hedonic hotspots, as well as their special hedonic enhancement functions. We report that channelrhodopsin stimulations within the two hedonic hotspots of rostral orbitofrontal and caudal insula each doubled the number of hedonic 'liking' reactions elicited by sucrose taste. Additionally, we confirmed that an intervening suppressive hedonic coldstrip stretches between them, where stimulation reduced 'liking' reactions. By contrast to the localization of hedonic hotspots for 'liking' enhancement, motivational 'wanting' for reward, measured as laser self-stimulation, was mediated by more widely distributed cortical sites in both hotspots and coldstrip.Significance Statement Orbitofrontal cortex and insula contain small 'hedonic hotspots' that increase 'liking' reactions to sweetness. Those hedonic hotspots were previously identified via local opioid/orexin microinjections, raising the danger they might be mere neurochemical artifacts of drug microinjections. We used optogenetic stimulation as an independent form of neuronal manipulation to assess whether they are instead robust neurobiological entities for hedonic enhancement. Our results confirm the OFC and insula 'hotspots' are robust hedonic entities: channelrhodopsin stimulation in rostromedial OFC or caudal insula hotspots enhanced 'liking'. We also confirmed a suppressive 'hedonic coldstrip' spans between the two hotspots, where stimulation oppositely suppressed 'liking'. By contrast, motivational 'wanting' sites to seek reward were anatomically more widespread and included sites in the hedonic coldstrip and hotspots.

Prenatal alcohol exposure (PAE) induces neurodevelopmental damage leading to fetal alcohol spectrum disorders (FASD) by altering both brain and ocular development. Recent data showed that PAE impairs brain cortical and retinal vasculature leading to defective positioning of interneurons. In the retina, PAE disturbs vascular development and the association of calretinin neurons with vessels. The NMDA receptor (NMDAR) is a major target of alcohol in the brain, and both ligand binding to NMDARs and the expression of NMDAR subunits are altered in FASD. Given that NMDAR is also expressed in endothelial cells and that glutamate stimulation of endothelial NMDAR (eNMDAR) regulates cortical interneuron positioning along blood vessels, we hypothesize that eNMDAR is critical for retinal vascular development and mediates PAE-induced defects. Using an in vivo model of FASD and transgenic mice lacking the endothelial GluN1 subunit of the NMDAR, this study aimed to characterize the neurovascular phenotype of the developing retina in mice of either sex. Our findings show that deletion of the eNMDAR reproduces key PAE-like alterations, including impaired progression of the superficial vascular plexus and changes in neuronal density, particularly in cells located closest to the retinal vasculature. Conversely, in eNMDAR knockout mice some of the retinal defects typically induced by PAE are prevented. Moreover, eNMDAR deletion led to an increased number of calretinin-positive interneurons contacting vessels and prevented the PAE-induced decrease. Together, these findings demonstrate that eNMDARs contribute to normal retinal neurovascular development and mediate, at least in part, the adverse effects of ethanol exposure in FASD.Significance statement Using a murine model of Fetal Alcohol Spectrum Disorder (FASD) and transgenic mice lacking the GluN1 subunit of the NMDA receptor specifically in endothelial cells (eNMDAR), this study demonstrates that eNMDAR plays a critical role in mediating prenatal alcohol exposure (PAE)-induced neurovascular abnormalities in the retina. Loss of eNMDAR alters the progression of the superficial vascular plexus and prevents the vascular impairments typically observed following PAE. In addition, eNMDAR deletion protects against PAE-induced neuronal damage, particularly affecting retinal ganglion cells, calbindin-positive, and calretinin-positive interneurons. Notably, this study identifies, for the first time, a role for endothelial NMDAR in regulating neurovascular interactions between retinal vessels and calretinin-positive neurons, highlighting this receptor as a key molecular mediator of ethanol-induced retinal damage.

Neurons across the visual system provide estimates of the visual features they encode. However, the reliability of those estimates can vary across the neuronal population. Here, we use information theory to provide a spatial map of how well neurons can distinguish ethologically-relevant visual stimuli across the entire larval zebrafish optic tectum (unknown sex), a brain region responsible for driving visually guided behaviour. We find that the ability of neurons to discriminate between stimuli is non-uniformly distributed across the tectum. Specifically, we show that information about local motion is preferentially encoded in the posterior tectum, whilst information about whole-field motion is preferentially encoded in the anterior tectum. This is achieved through two systematic changes along the anterior-posterior axis of the tectum: (i) a change in the number of neurons that discriminate between stimuli and (ii) a change in how well each neuron can discriminate between stimuli. By classifying neurons into distinct subtypes based on their response properties we uncovered a small group of neurons that are spatially localised to specific regions of the tectum and are able to discriminate between visual stimuli in a highly reliable manner. Furthermore we show these spatial biases are enhanced when using population activity to decode the visual stimuli. Our results highlight the importance of implementing information theoretic approaches to assess visual responses and provide a novel description of regional specialisation in the zebrafish optic tectum.Significance Statement To understand how neurons encode information about sensory stimuli it is important to establish which features they respond to and how reliably they respond. However, many studies analyse trial-averaged neuronal responses which convey no information about response reliability. We overcome this shortcoming by using an approach that considers feature selectivity along with trial-to-trial response variability allowing us to link which feature a neuron is encoding and how well it is encoded.Using this method we uncovered a high degree of spatial organisation within the zebrafish optic tectum such that different visual features are encoded preferentially within different regions. Since the tectum is topographically mapped, the spatial segregation of visual processing implies that visual objects are encoded in a location-dependent manner.