ex Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus By www.jneurosci.org Published On :: 2013-05-01 Timothy J. SchoenfeldMay 1, 2013; 33:7770-7777BehavioralSystemsCognitive Full Article
ex Readiness Potential and Neuronal Determinism: New Insights on Libet Experiment By www.jneurosci.org Published On :: 2018-01-24 Karim FifelJan 24, 2018; 38:784-786Journal Club Full Article
ex Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control By www.jneurosci.org Published On :: 2007-02-28 William W. SeeleyFeb 28, 2007; 27:2349-2356BehavioralSystemsCognitive Full Article
ex Nurture versus Nature: Long-Term Impact of Forced Right-Handedness on Structure of Pericentral Cortex and Basal Ganglia By www.jneurosci.org Published On :: 2010-03-03 Stefan KlöppelMar 3, 2010; 30:3271-3275BRIEF COMMUNICATION Full Article
ex The Representation of Semantic Information Across Human Cerebral Cortex During Listening Versus Reading Is Invariant to Stimulus Modality By www.jneurosci.org Published On :: 2019-09-25 Fatma DenizSep 25, 2019; 39:7722-7736BehavioralSystemsCognitive Full Article
ex Astrocytes Modulate Baroreflex Sensitivity at the Level of the Nucleus of the Solitary Tract By www.jneurosci.org Published On :: 2020-04-08 Svetlana MastitskayaApr 8, 2020; 40:3052-3062Systems/Circuits Full Article
ex White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging By www.jneurosci.org Published On :: 2014-11-12 Georg S. KranzNov 12, 2014; 34:15466-15475Systems/Circuits Full Article
ex Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence By www.jneurosci.org Published On :: 2019-03-06 Catherine OrrMar 6, 2019; 39:1817-1827BehavioralSystemsCognitive Full Article
ex Interactions of Top-Down and Bottom-Up Mechanisms in Human Visual Cortex By www.jneurosci.org Published On :: 2011-01-12 Stephanie McMainsJan 12, 2011; 31:587-597BehavioralSystemsCognitive Full Article
ex An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex By www.jneurosci.org Published On :: 2014-09-03 Ye ZhangSep 3, 2014; 34:11929-11947Cellular Full Article
ex Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex By www.jneurosci.org Published On :: 2017-05-24 Michele BellesiMay 24, 2017; 37:5263-5273Cellular Full Article
ex The Encoding of Sound Source Elevation in the Human Auditory Cortex By www.jneurosci.org Published On :: 2018-03-28 Régis TrapeauMar 28, 2018; 38:3252-3264BehavioralSystemsCognitive Full Article
ex The Fusiform Face Area: A Module in Human Extrastriate Cortex Specialized for Face Perception By www.jneurosci.org Published On :: 1997-06-01 Nancy KanwisherJun 1, 1997; 17:4302-4311Articles Full Article
ex Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons By www.jneurosci.org Published On :: 1996-03-15 RJ WentholdMar 15, 1996; 16:1982-1989Articles Full Article
ex Neural Mechanisms of Visual Working Memory in Prefrontal Cortex of the Macaque By www.jneurosci.org Published On :: 1996-08-15 Earl K. MillerAug 15, 1996; 16:5154-5167Articles Full Article
ex Experience-Dependent Plasticity of Binocular Responses in the Primary Visual Cortex of the Mouse By www.jneurosci.org Published On :: 1996-05-15 Joshua A. GordonMay 15, 1996; 16:3274-3286Articles Full Article
ex The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells By www.jneurosci.org Published On :: 1987-07-01 RU MullerJul 1, 1987; 7:1951-1968Articles Full Article
ex Quantitative Ultrastructural Analysis of Hippocampal Excitatory Synapses By www.jneurosci.org Published On :: 1997-08-01 Thomas SchikorskiAug 1, 1997; 17:5858-5867Articles Full Article
ex Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems By www.jneurosci.org Published On :: 1998-12-01 Christelle PeyronDec 1, 1998; 18:9996-10015Articles Full Article
ex {alpha}-Band Electroencephalographic Activity over Occipital Cortex Indexes Visuospatial Attention Bias and Predicts Visual Target Detection By www.jneurosci.org Published On :: 2006-09-13 Gregor ThutSep 13, 2006; 26:9494-9502BehavioralSystemsCognitive Full Article
ex Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex By www.jneurosci.org Published On :: 2005-01-05 Chris EnglundJan 5, 2005; 25:247-251BRIEF COMMUNICATION Full Article
ex Linearity and Normalization in Simple Cells of the Macaque Primary Visual Cortex By www.jneurosci.org Published On :: 1997-11-01 Matteo CarandiniNov 1, 1997; 17:8621-8644Articles Full Article
ex Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage By www.jneurosci.org Published On :: 2002-08-01 Jessica A. GorskiAug 1, 2002; 22:6309-6314BRIEF COMMUNICATION Full Article
ex High-Level Neuronal Expression of A{beta}1-42 in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque Formation By www.jneurosci.org Published On :: 2000-06-01 Lennart MuckeJun 1, 2000; 20:4050-4058Cellular Full Article
ex Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex By www.jneurosci.org Published On :: 1982-01-01 EL BienenstockJan 1, 1982; 2:32-48Articles Full Article
ex Highly Selective Receptive Fields in Mouse Visual Cortex By www.jneurosci.org Published On :: 2008-07-23 Cristopher M. NiellJul 23, 2008; 28:7520-7536BehavioralSystemsCognitive Full Article
ex Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control By www.jneurosci.org Published On :: 2007-02-28 William W. SeeleyFeb 28, 2007; 27:2349-2356BehavioralSystemsCognitive Full Article
ex An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex By www.jneurosci.org Published On :: 2014-09-03 Ye ZhangSep 3, 2014; 34:11929-11947Cellular Full Article
ex The Fusiform Face Area: A Module in Human Extrastriate Cortex Specialized for Face Perception By www.jneurosci.org Published On :: 1997-06-01 Nancy KanwisherJun 1, 1997; 17:4302-4311Articles Full Article
ex Le Comité de Bâle finalise sa revue du traitement réglementaire des expositions aux actifs souverains sans modifier les règles existantes et publie un document de discussion By www.bis.org Published On :: 2017-12-07T16:00:00Z French translation of the press release about the Basel Committee publishing a discussion paper on "The regulatory treatment of sovereign exposures" (7 December 2017) Full Article
ex Questions fréquemment posées sur les exigences de fonds propres en regard du risque de marché By www.bis.org Published On :: 2018-03-28T13:34:00Z French translation of "Frequently asked questions on market risk capital requirements" by the Basel Committee, March 2018. Full Article
ex Exigences de communication financière au titre du troisième pilier - dispositif révisé By www.bis.org Published On :: 2018-12-11T10:43:00Z French translation of "Pillar 3 disclosure requirements - updated framework", December 2018 Full Article
ex Wintrust Financial Corporation Announces Executive Officer Promotions By www.snl.com Published On :: Tue, 28 Jan 2020 21:10:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
ex New ‘Great Exhibition at Home’ challenge launched to inspire young innovators By www.raeng.org.uk Published On :: Thu, 26 Mar 2020 16:03:57 +00:00 Full Article
ex Interview with Brazil's EXAME By www.bis.org Published On :: 2019-10-28T16:00:00Z Original quotes from interview by Mr Agustin Carstens, General Manager of the BIS, with Exame, conducted by Mr Felipe Serrano on 9 October 2019 and published on 24 October 2019. Full Article
ex The expectations on central banks are simply too great By www.bis.org Published On :: 2019-11-21T14:44:00Z Original quotes from interview with Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, in Germany's Boerzen-Zeitung, conducted by Mr Mark Schroers and published on 21 November 2019. Full Article
ex Lessons from 25 years of the Bank of Mexico's independence By www.bis.org Published On :: 2019-11-29T09:00:00Z Speech by Dr Agustín Carstens at the celebration of 25 years of Bank of Mexico independence, Mexico City, 22 November 2019. Full Article
ex Exiting low inflation traps by "consensus": nominal wages and price stability By www.bis.org Published On :: 2019-12-20T09:00:00Z Exiting low inflation traps by "consensus": nominal wages and price stability - Speech by Luiz A Pereira da Silva and Benoît Mojon, based on the keynote speech at the Eighth High-level Policy Dialogue between the Eurosystem and Latin American Central Banks, Cartagena de Indias, Colombia, 28-29 November 2019. Full Article
ex Cross Recruitment of Domain-Selective Cortical Representations Enables Flexible Semantic Knowledge By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Knowledge about objects encompasses not only their prototypical features but also complex, atypical, semantic knowledge (e.g., "Pizza was invented in Naples"). This fMRI study of male and female human participants combines univariate and multivariate analyses to consider the cortical representation of this more complex semantic knowledge. Using the categories of food, people, and places, this study investigates whether access to spatially related geographic semantic knowledge (1) involves the same domain-selective neural representations involved in access to prototypical taste knowledge about food; and (2) elicits activation of neural representations classically linked to places when this geographic knowledge is accessed about food and people. In three experiments using word stimuli, domain-relevant and atypical conceptual access for the categories food, people, and places were assessed. Results uncover two principles of semantic representation: food-selective representations in the left insula continue to be recruited when prototypical taste knowledge is task-irrelevant and under conditions of high cognitive demand; access to geographic knowledge for food and people categories involves the additional recruitment of classically place-selective parahippocampal gyrus, retrosplenial complex, and transverse occipital sulcus. These findings underscore the importance of object category in the representation of a broad range of knowledge, while showing how the cross recruitment of specialized representations may endow the considerable flexibility of our complex semantic knowledge. SIGNIFICANCE STATEMENT We know not only stereotypical things about objects (an apple is round, graspable, edible) but can also flexibly combine typical and atypical features to form complex concepts (the metaphorical role an apple plays in Judeo-Christian belief). In this fMRI study, we observe that, when atypical geographic knowledge is accessed about food dishes, domain-selective sensorimotor-related cortical representations continue to be recruited, but that regions classically associated with place perception are additionally engaged. This interplay between categorically driven representations, linked to the object being accessed, and the flexible recruitment of semantic stores linked to the content being accessed, provides a potential mechanism for the broad representational repertoire of our semantic system. Full Article
ex Integration of Swimming-Related Synaptic Excitation and Inhibition by olig2+ Eurydendroid Neurons in Larval Zebrafish Cerebellum By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor olig2. Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2+ neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2+ ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2+ cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning. SIGNIFICANCE STATEMENT The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates. Full Article
ex Astrocytes Modulate Baroreflex Sensitivity at the Level of the Nucleus of the Solitary Tract By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits of the brainstem. The neurophysiology and neuroanatomy of these reflex pathways are well understood, however, the mechanisms and functional significance of autonomic circuit modulation by glial cells remain largely unknown. In the experiments conducted in male laboratory rats we show that astrocytes of the nucleus of the solitary tract (NTS), the brain area that receives and integrates sensory information from the heart and blood vessels, respond to incoming afferent inputs with [Ca2+]i elevations. Astroglial [Ca2+]i responses are triggered by transmitters released by vagal afferents, glutamate acting at AMPA receptors and 5-HT acting at 5-HT2A receptors. In conscious freely behaving animals blockade of Ca2+-dependent vesicular release mechanisms in NTS astrocytes by virally driven expression of a dominant-negative SNARE protein (dnSNARE) increased baroreflex sensitivity by 70% (p < 0.001). This effect of compromised astroglial function was specific to the NTS as expression of dnSNARE in astrocytes of the ventrolateral brainstem had no effect. ATP is considered the principle gliotransmitter and is released by vesicular mechanisms blocked by dnSNARE expression. Consistent with this hypothesis, in anesthetized rats, pharmacological activation of P2Y1 purinoceptors in the NTS decreased baroreflex gain by 40% (p = 0.031), whereas blockade of P2Y1 receptors increased baroreflex gain by 57% (p = 0.018). These results suggest that glutamate and 5-HT, released by NTS afferent terminals, trigger Ca2+-dependent astroglial release of ATP to modulate baroreflex sensitivity via P2Y1 receptors. These data add to the growing body of evidence supporting an active role of astrocytes in brain information processing. SIGNIFICANCE STATEMENT Cardiorespiratory reflexes maintain autonomic balance and ensure cardiovascular health. Impaired baroreflex may contribute to the development of cardiovascular disease and serves as a robust predictor of cardiovascular and all-cause mortality. The data obtained in this study suggest that astrocytes are integral components of the brainstem mechanisms that process afferent information and modulate baroreflex sensitivity via the release of ATP. Any condition associated with higher levels of "ambient" ATP in the NTS would be expected to decrease baroreflex gain by the mechanism described here. As ATP is the primary signaling molecule of glial cells (astrocytes, microglia), responding to metabolic stress and inflammatory stimuli, our study suggests a plausible mechanism of how the central component of the baroreflex is affected in pathological conditions. Full Article
ex Neural Correlates of Strategy Switching in the Macaque Orbital Prefrontal Cortex By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 We can adapt flexibly to environment changes and search for the most appropriate rule to a context. The orbital prefrontal cortex (PFo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. To better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey PFo when a strategy is changed. In the strategy task, we used a visual cue to instruct two male rhesus monkeys either to repeat their most recent choice (i.e., stay strategy) or to change it (i.e., shift strategy). To identify the strategy switching-related signal, we compared nonswitch and switch trials, which cued the same or a different strategy from the previous trial, respectively. We found that the switching-related signal emerged during the cue presentation and it was combined with the strategy signal in a subpopulation of cells. Moreover, the error analysis showed that the activity of the switch-related cells reflected whether the monkeys erroneously switched or not the strategy, rather than what was required for that trial. The function of the switching signal could be to prompt the use of different strategies when older strategies are no longer appropriate, conferring the ability to adapt flexibly to environmental changes. In our task, the switching signal might contribute to the implementation of the strategy cued, overcoming potential interference effects from the strategy previously cued. Our results support the idea that ascribes to PFo an important role for behavioral flexibility. SIGNIFICANCE STATEMENT We can flexibly adapt our behavior to a changing environment. One of the prefrontal areas traditionally associated with the ability to adapt to new contingencies is the orbital prefrontal cortex (PFo). We analyzed the switching related activity using a strategy task in which two rhesus monkeys were instructed by a visual cue either to repeat or change their most recent choice, respectively using a stay or a shift strategy. We found that PFo neurons were modulated by the strategy switching signal, pointing to the importance of PFo in behavioral flexibility by generating control over the switching of strategies. Full Article
ex Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans. SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale. Full Article
ex Interneuron NMDA Receptor Ablation Induces Hippocampus-Prefrontal Cortex Functional Hypoconnectivity after Adolescence in a Mouse Model of Schizophrenia By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia's pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone. SIGNIFICANCE STATEMENT NMDAR hypofunction in cortical interneurons has been linked to schizophrenia pathophysiology. How a dysfunction of GABAergic cortical interneurons interacts with maturation during adolescence has not been clarified yet. Here, we demonstrate in vivo that early postnatal ablation of the NMDAR in corticolimbic interneurons results in an overactive but desynchronized PFC before adolescence. Final postnatal maturation during this stage outspreads the impact of the genetic manipulation toward a functional disconnection of the ventral hippocampal-prefrontal pathway, probably as a consequence of an exacerbated propensity toward hippocampal-evoked depotentiation plasticity. Our results demonstrate a complex interaction between genetic and developmental factors affecting cortical interneurons and PFC function. Full Article
ex The Effect of Counterfactual Information on Outcome Value Coding in Medial Prefrontal and Cingulate Cortex: From an Absolute to a Relative Neural Code By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Adaptive coding of stimuli is well documented in perception, where it supports efficient encoding over a broad range of possible percepts. Recently, a similar neural mechanism has been reported also in value-based decision, where it allows optimal encoding of vast ranges of values in PFC: neuronal response to value depends on the choice context (relative coding), rather than being invariant across contexts (absolute coding). Additionally, value learning is sensitive to the amount of feedback information: providing complete feedback (both obtained and forgone outcomes) instead of partial feedback (only obtained outcome) improves learning. However, it is unclear whether relative coding occurs in all PFC regions and how it is affected by feedback information. We systematically investigated univariate and multivariate feedback encoding in various mPFC regions and compared three modes of neural coding: absolute, partially-adaptive and fully-adaptive. Twenty-eight human participants (both sexes) performed a learning task while undergoing fMRI scanning. On each trial, they chose between two symbols associated with a certain outcome. Then, the decision outcome was revealed. Notably, in one-half of the trials participants received partial feedback, whereas in the other half they got complete feedback. We used univariate and multivariate analysis to explore value encoding in different feedback conditions. We found that both obtained and forgone outcomes were encoded in mPFC, but with opposite sign in its ventral and dorsal subdivisions. Moreover, we showed that increasing feedback information induced a switch from absolute to relative coding. Our results suggest that complete feedback information enhances context-dependent outcome encoding. SIGNIFICANCE STATEMENT This study offers a systematic investigation of the effect of the amount of feedback information (partial vs complete) on univariate and multivariate outcome value encoding, within multiple regions in mPFC and cingulate cortex that are critical for value-based decisions and behavioral adaptation. Moreover, we provide the first comparison of three possible models of neural coding (i.e., absolute, partially-adaptive, and fully-adaptive coding) of value signal in these regions, by using commensurable measures of prediction accuracy. Taken together, our results help build a more comprehensive picture of how the human brain encodes and processes outcome value. In particular, our results suggest that simultaneous presentation of obtained and foregone outcomes promotes relative value representation. Full Article
ex Ventral Hippocampal Input to the Prelimbic Cortex Dissociates the Context from the Cue Association in Trace Fear Memory By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations. SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning. Full Article
ex Comparative Transcriptomic Analyses of Developing Melanocortin Neurons Reveal New Regulators for the Anorexigenic Neuron Identity By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression or energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied. SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in developing and adult POMC neurons. Our studies establish a previously unrecognized role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Full Article