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SummaryBasal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population—but not cholinergic neurons—were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity.

Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.

The revolution in neuroscientific data acquisition is creating an analysis challenge. We propose leveraging cloud-computing technologies to enable large-scale neurodata storing, exploring, analyzing, and modeling. This utility will empower scientists globally to generate and test theories of brain function and dysfunction.

SummarySerotonin dysfunction is implicated in many neuropsychiatric disorders yet the precise behavioral functions of this neuromodulator are not well understood. A new study employs optogenetic methods to activate serotonin neurons during an effort-demanding waiting behavior and demonstrates that serotonin release increases patience, the capacity for self-control.

A summary of results from the micro-census carried out in 1984 in Hungary is presented. Information is first provided on methodology, data collection, the sampling method used, data processing, and dissemination of results. Summary data are included on population characteristics, including occupation and educational status; the number and composition of households; and housing. Information is also included on the health of the population, commuting, child care, and other aspects of social welfare. (summary in ENG, RUS)

There is increasing evidence that the social and cultural characteristics of psychiatric patients have been changing over time. 1,2 It is important from a professional and public policy point of view to understand better the nature of these changes, and to what they are related. This paper presents data showing that: 1) psychiatric care is increasingly reaching patients of lower socio economic status, and 2) changes in patient characteristics are related to the growth in the pro portion of psychiatric care given in organisationally based non-private practice settings.

The methodology used in the 1984 microcensus of Hungary is described. The main innovation involved the use of preprinted personal data from the National Population Registration Office which meant that enumerators had prepared questionnaires available before undertaking census interviews. A trial census held in 1984 in Gyor County is also described. (ANNOTATION)

Atopic dermatitis, a disease which causes severe itching and scratching, often begins in the first few months of life, and may continue to the adult period, with exacerbations and remissions. The presence of an itching eruption from early life raises such questions as: How does this affect maturation of defenses against irritation? Does early itch-scratch lead to fixation, and of what does this consist? By careful observation of reactions to skin stimulation, it is possible to obtain some information pertinent to these and related problems. Earlier studies10,11,16of responses of subjects to stroking the forehead with cotton for two minutes have proved to be useful indicators of how a person reacts to mild irritation, of how this irritation is a source of erotic pleasure, and of how irritation is finally mastered. We found that people who are emotionally volatile and labile tended to

Problems of communicating therapeutically with mothers of psychotic children are explored from the vantage point of subjective reactions which the mothers' verbal interview behavior evokes in therapists. Comparison is made with therapists' reactions elicited by a control group of mothers of less severely disturbed children. Significant differences appear in the intensity of the aroused, unconscious involvement and in the clarity of the images the mothers conveyed about themselves and their relationship to their child.

Computational psychiatry is an emerging field that examines phenomena in mental illness using formal techniques from computational neuroscience, mathematical psychology, and machine learning. These techniques can be used in a theory-driven manner to gain insight into neural or cognitive processes and in a data-driven way to identify predictive and explanatory relationships in complex datasets. The approaches complement each other: theory-driven models can be used to infer mechanisms, and the resulting measurements can be used in data-driven approaches for prediction. Recent computational studies have successfully described and measured novel mechanisms in a range of disorders, have framed disorders in new and informative ways, and have identified predictors of treatment response. These methods hold the potential to improve identification of relevant clinical variables and could be superior to classification based on traditional behavioral or neural data alone. However, these promising results have been slow to influence clinical practice or to improve patient outcomes.

The basal forebrain (BF) houses major ascending projections to the entire neocortex that have long been implicated in arousal, learning, and attention. The disruption of the BF has been linked with major neurological disorders, such as coma and Alzheimer's disease, as well as in normal cognitive aging. Although it is best known for its cholinergic neurons, the BF is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific BF cell types have led to a renaissance in the study of the BF and are beginning to yield new insights about cell-type-specific circuit mechanisms during behavior. These approaches enable us to determine the behavioral conditions under which cholinergic and noncholinergic BF neurons are activated and how they control cortical processing to influence behavior. Here we discuss recent advances that have expanded our knowledge about this poorly understood brain region and laid the foundation for future cell-type-specific manipulations to modulate arousal, attention, and cortical plasticity in neurological disorders.SIGNIFICANCE STATEMENTAlthough the basal forebrain is best known for, and often equated with, acetylcholine-containing neurons that provide most of the cholinergic innervation of the neocortex, it is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific cell types in the basal forebrain have led to a renaissance in this field and are beginning to dissect circuit mechanisms in the basal forebrain during behavior. This review discusses recent advances in the roles of basal forebrain cholinergic and noncholinergic neurons in cognition via their dynamic modulation of cortical activity.

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscience'' and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.

We demonstrate the first visible-range nanophotonic switch network and create an implantable probe for in-vivo deep-brain stimulation. The probe enables stimulation patterns of single neurons with the timing and spatial precision to decode animal behavior.