Warren Buffet once said, "Only when the tide goes out do you discover who's been swimming naked." You can cover over a host of sins when times are good, but bad or unsafe practices will be exposed when times are rough. Time and experience have borne out the accuracy of this witticism in the financial arena -- and we're now seeing its applicability to the intersection of infosec and COVID-19.

In today's evolving business environment, every operational decision is critical -- and that includes best practices for managing the customer journey. The CRM platform is an integral part of the process. In fact, 91 percent of companies with more than 11 employees use a CRM system. Because of the time it saves and the structure CRM delivers, it can seem daunting for businesses to make a switch.

Edge conditions and the change they drive are fascinating. Some people use the word "margin" because it's at the margin that things change. A situation exists more or less in equilibrium with the rest of its environment until in one way or another the stresses become so great that change happens. We have lots of metaphors, like "tipping point" and "the straw that broke the camel's back."

These days are either the most trying time for encouraging employee engagement or the best we could expect. With so many people working remotely, many businesses need extra ways to communicate with the rank and file, and this might present a prime opportunity to try new things. We make a big deal of engaging the customer, and in most CRM circles engagement outranks simple customer experience.

Adobe just announced what it calls the first digital economy index. It seems like it's modeled after other indices usually kept by the federal government to measure economic output and consumption. The Adobe index captures only consumer consumption behavior though. Some of its insights include new shopping behavior, such as which products have become hot items or decreased in popularity over time.

Merchants soon will be able to sell products on Google Shopping at no charge. Previously, they had to pay per click, but the cost was not fixed. There was no minimum, but they had to set a maximum for ad spend and Google would stop displaying their ads once the maximum was reached. Starting next week, search results on the Google Shopping tab will consist primarily of free product listings.

Contact tracing is a big job, like trying to drain an ocean with a teaspoon. It involves finding people who have been exposed to the coronavirus and testing them to determine if they are infected or are carriers. Public health officials then can take necessary steps to prevent the virus' spread. It's a perfect fit for CRM, and Salesforce's core technology is coming to the forefront.

The enterprise IT environment is complex. Many systems, technologies and practices developed at various times coexist in the same world. With expectations for technological advancements at their peak, we're tasked with enabling these systems to work together harmoniously to support the continuous sharing of information. Systems and data must connect as if all information were native to each.

Oracle and Zoom just entered a deal that for once is more about technological audacity than about dollars -- a partnership to host Zoom on Oracle Cloud Infrastructure. In just a few months -- basically since the beginning of the novel coronavirus pandemic -- Zoom has seen demand for its service grow from about 10 million daily meeting participants to more than 300 million.

02020-02-05: Snow in Pennsylvania and New York

Speech by Mr Agustín Carstens, General Manager of the BIS, at the Eurofi Financial Forum, Helsinki, 12 September 2019.

Welcoming remarks by Mr Fernando Restoy, Chairman, Financial Stability Institute, Bank for International Settlements, at the FSI-IADI conference on crisis management, resolution and deposit insurance: what's next and how to prepare, Basel, 4 September 2019.

Speech by Mr Agustín Carstens, General Manager of the BIS, at the Founding Ceremony, Swiss Centre BIS Innovation Hub, Zurich, 8 October 2019.

Op-ed by Mr Agustín Carstens, General Manager of the BIS, published in The Business Times Singapore, 13 November 2019.

Keynote speech by Mr Agustín Carstens, General Manager of the BIS, at the 55th SEACEN Governors' Conference and High-level Seminar on "Data and technology: embracing innovation", Singapore, 14 November 2019.

Lecture by Mr Agustín Carstens, General Manager of the BIS, at the Princeton University, Princeton, New Jersey, 5 December 2019.

Op-ed by Agustín Carstens published in the Financial Times on 29 March 2020.

Story: As many as 12 million computers worldwide have been infected with a highly encrypted computer worm called Conficker. Writer Mark Bowden details how Conficker was discovered, how it works, and the ongoing programming battle to bring down Conficker in his book Worm: The First Digital World War.

Story: Several apostles affiliated with the movement helped organize or spoke at Rick Perry's recent prayer rally. A leading apostle, C. Peter Wagner, talks about the movement and its missions, which include acquiring leadership positions in government, the media, and arts and entertainment.

Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial. Here, we provide genetic evidence that Drp1 inhibition is neuroprotective. Drp1 is activated by dephosphorylation of an inhibitory phosphorylation site, Ser637. We identify Bβ2, a mitochondria-localized protein phosphatase 2A (PP2A) regulatory subunit, as a neuron-specific Drp1 activator in vivo. Bβ2 KO mice of both sexes display elongated mitochondria in neurons and are protected from cerebral ischemic injury. Functionally, deletion of Bβ2 and maintained Drp1 Ser637 phosphorylation improved mitochondrial respiratory capacity, Ca²⁺ homeostasis, and attenuated superoxide production in response to ischemia and excitotoxicity in vitro and ex vivo. Last, deletion of Bβ2 rescued excessive stroke damage associated with dephosphorylation of Drp1 S637 and mitochondrial fission. These results indicate that the state of mitochondrial connectivity and PP2A/Bβ2-mediated dephosphorylation of Drp1 play a critical role in determining the severity of cerebral ischemic injury. Therefore, Bβ2 may represent a target for prophylactic neuroprotective therapy in populations at high risk of stroke.

SIGNIFICANCE STATEMENT With recent advances in clinical practice including mechanical thrombectomy up to 24 h after the ischemic event, there is resurgent interest in neuroprotective stroke therapies. In this study, we demonstrate reduced stroke damage in the brain of mice lacking the Bβ2 regulatory subunit of protein phosphatase 2A, which we have shown previously acts as a positive regulator of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Importantly, we provide evidence that deletion of Bβ2 can rescue excessive ischemic damage in mice lacking the mitochondrial PKA scaffold AKAP1, apparently via opposing effects on Drp1 S637 phosphorylation. These results highlight reversible phosphorylation in bidirectional regulation of Drp1 activity and identify Bβ2 as a potential pharmacological target to protect the brain from stroke injury.

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.

A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning.

SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner.

Traditional views of sensorimotor adaptation (i.e., adaptation of movements to perturbed sensory feedback) emphasize the role of automatic, implicit correction of sensory prediction errors. However, latent memories formed during sensorimotor adaptation, manifest as improved relearning (e.g., savings), have recently been attributed to strategic corrections of task errors (failures to achieve task goals). To dissociate contributions of task errors and sensory prediction errors to latent sensorimotor memories, we perturbed target locations to remove or enforce task errors during learning and/or test, with male/female human participants. Adaptation improved after learning in all conditions where participants were permitted to correct task errors, and did not improve whenever we prevented correction of task errors. Thus, previous correction of task errors was both necessary and sufficient to improve adaptation. In contrast, a history of sensory prediction errors was neither sufficient nor obligatory for improved adaptation. Limiting movement preparation time showed that the latent memories driven by learning to correct task errors take at least two forms: a time-consuming but flexible component, and a rapidly expressible, inflexible component. The results provide strong support for the idea that movement corrections driven by a failure to successfully achieve movement goals underpin motor memories that manifest as savings. Such persistent memories are not exclusively mediated by time-consuming strategic processes but also comprise a rapidly expressible but inflexible component. The distinct characteristics of these putative processes suggest dissociable underlying mechanisms, and imply that identification of the neural basis for adaptation and savings will require methods that allow such dissociations.

SIGNIFICANCE STATEMENT Latent motor memories formed during sensorimotor adaptation manifest as improved adaptation when sensorimotor perturbations are reencountered. Conflicting theories suggest that this "savings" is underpinned by different mechanisms, including a memory of successful actions, a memory of errors, or an aiming strategy to correct task errors. Here we show that learning to correct task errors is sufficient to show improved subsequent adaptation with respect to naive performance, even when tested in the absence of task errors. In contrast, a history of sensory prediction errors is neither sufficient nor obligatory for improved adaptation. Finally, we show that latent sensorimotor memories driven by task errors comprise at least two distinct components: a time-consuming, flexible component, and a rapidly expressible, inflexible component.

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-HT_2A 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.

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.

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.

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

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.

It has been proposed that people can generate probabilistic predictions at multiple levels of representation during language comprehension. We used magnetoencephalography (MEG) and electroencephalography (EEG), in combination with representational similarity analysis, to seek neural evidence for the prediction of animacy features. In two studies, MEG and EEG activity was measured as human participants (both sexes) read three-sentence scenarios. Verbs in the final sentences constrained for either animate or inanimate semantic features of upcoming nouns, and the broader discourse context constrained for either a specific noun or for multiple nouns belonging to the same animacy category. We quantified the similarity between spatial patterns of brain activity following the verbs until just before the presentation of the nouns. The MEG and EEG datasets revealed converging evidence that the similarity between spatial patterns of neural activity following animate-constraining verbs was greater than following inanimate-constraining verbs. This effect could not be explained by lexical-semantic processing of the verbs themselves. We therefore suggest that it reflected the inherent difference in the semantic similarity structure of the predicted animate and inanimate nouns. Moreover, the effect was present regardless of whether a specific word could be predicted, providing strong evidence for the prediction of coarse-grained semantic features that goes beyond the prediction of individual words.

SIGNIFICANCE STATEMENT Language inputs unfold very quickly during real-time communication. By predicting ahead, we can give our brains a "head start," so that language comprehension is faster and more efficient. Although most contexts do not constrain strongly for a specific word, they do allow us to predict some upcoming information. For example, following the context of "they cautioned the...," we can predict that the next word will be animate rather than inanimate (we can caution a person, but not an object). Here, we used EEG and MEG techniques to show that the brain is able to use these contextual constraints to predict the animacy of upcoming words during sentence comprehension, and that these predictions are associated with specific spatial patterns of neural activity.

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.

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomic, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to postsynaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell types. We observed little or no transport, however, through neuromodulatory projections (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, although its capacity for retrograde transport currently limits its use to unidirectional circuits.

SIGNIFICANCE STATEMENT The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons, and (2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.

Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y₅ receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons. Repeated treatment of OTCs with NPY followed by an identical treatment with CRF, or vice versa, inhibited or reversed all structural changes in OTCs. These structural responses to NPY or CRF required calcineurin or CaMKII, respectively. Finally, repeated intra-BLA injections of NPY or a Y₅ receptor agonist increased social interaction, a validated behavior for anxiety, and recapitulated structural changes in BLA neurons seen in OTCs, while a Y₅ receptor antagonist prevented NPY's effects both on behavior and on structure. These results implicate the Y₅ receptor in the long-term, anxiolytic-like effects of NPY in the BLA, consistent with an intrinsic role in stress buffering, and highlight a remarkable mechanism by which BLA neurons may adapt to different levels of stress. Moreover, BLA OTCs offer a robust model to study mechanisms associated with resilience and vulnerability to stress in BLA.

SIGNIFICANCE STATEMENT Within the basolateral amygdala (BLA), neuropeptide Y (NPY) is associated with buffering the neural stress response induced by corticotropin releasing factor, and promoting stress resilience. We used a novel organotypic slice culture model of BLA, complemented with in vivo studies, to examine the cellular mechanisms associated with the actions of NPY. In organotypic slice cultures, repeated NPY treatment reduces the complexity of the dendritic extent of anxiogenic BLA principal neurons, making them less excitable. NPY, via activation of Y5 receptors, additionally inhibits and reverses the increases in dendritic extent and excitability induced by the stress hormone, corticotropin releasing factor. This NPY-mediated neuroplasticity indicates that resilience or vulnerability to stress may thus involve neuropeptide-mediated dendritic remodeling in BLA principal neurons.

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.

Giving birth triggers a wide repertoire of physiological and behavioral changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the CNS, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca²⁺ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine whether they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, I_h, possibly through unmasking as dopamine release drops during nursing, may partially explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.

SIGNIFICANCE STATEMENT Motherhood requires profound behavioral and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that, during lactation, neuroendocrine dopamine neurons, the "TIDA" cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully on weaning. We further provide evidence that a specific conductance (I_h) contributes to the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.