Specific Basal Forebrain-Cortical Cholinergic Circuits Coordinate Cognitive Operations.

Based on recent molecular genetics, as well as functional and quantitative anatomical studies, the basal forebrain (BF) cholinergic projections, once viewed as a diffuse system, are emerging as being remarkably specific in connectivity. Acetylcholine (ACh) can rapidly and selectively modulate activity of specific circuits and ACh release can be coordinated in multiple areas that are related to particular aspects of cognitive processing. This review discusses how a combination of multiple new approaches with more established techniques are being used to finally reveal how cholinergic neurons, together with other BF neurons, provide temporal structure for behavior, contribute to local cortical state regulation, and coordinate activity between different functionally related cortical circuits. ACh selectively modulates dynamics for encoding and attention within individual cortical circuits, allows for important transitions during sleep, and shapes the fidelity of sensory processing by changing the correlation structure of neural firing. The importance of this system for integrated and fluid behavioral function is underscored by its disease-modifying role; the demise of BF cholinergic neurons has long been established in Alzheimer's disease and recent studies have revealed the involvement of the cholinergic system in modulation of anxiety-related circuits. Therefore, the BF cholinergic system plays a pivotal role in modulating the dynamics of the brain during sleep and behavior, as foretold by the intricacies of its anatomical map.

Functional architecture of the forebrain cholinergic system in rodents.

The basal forebrain cholinergic system (BFCS) participates in functions that are global across the brain, such as sleep-wake cycles, but also participates in capacities that are more behaviorally and anatomically specific, including sensory perception. To better understand the underlying organization principles of the BFCS, more and higher quality anatomical data and analysis is needed. Here, we created a "virtual Basal Forebrain", combining data from numerous rats with cortical retrograde tracer injections into a common 3D reference coordinate space and developed a "spatial density correlation" methodology to analyze patterns in BFCS cortical projection targets, revealing that the BFCS is organized into three principal networks: somatosensory-motor, auditory, and visual. Within each network, clusters of cholinergic cells with increasing complexity innervate cortical targets. These networks represent hierarchically organized building blocks that may enable the BFCS to coordinate spatially selective signaling, including parallel modulation of multiple functionally interconnected yet diverse groups of cortical areas.

Are modern health worries associated with somatosensory amplification, environmental attribution style, and commitment to complementary and alternative medicine?

Relationship among modern health worries (MHWs), somatosensory amplification (SSA), and attributional styles was investigated in a cross-sectional questionnaire study. A total of 99 university students, 104 patients visiting their General Practitioners, and 102 future alternative therapists completed questionnaires assessing MHWs, SSA, negative affect (NA), and psychological, somatic and normalizing (environmental) attribution styles. Significant correlation between SSA and MHWs was found in all three samples. MHWs and psychological attribution style were significantly associated with Complementary and Alternative Medicine (CAM)-orientation in the regression equation even after controlling for SSA, NA, and sociodemographic variables. MHWs were independent from any attribution styles in the student and patient samples, while significant correlations with all three styles were found in the CAM group. Previously described association between MHWs and SSA was replicated in three different samples. The connection between MHWs and CAM preference seems to be independent from SSA, NA or any particular attribution style.

Contribution of the basal forebrain to corticocortical network interactions.

Basal forebrain (BF) cholinergic neurons provide the cerebral cortex with acetylcholine. Despite the long-established involvement of these cells in sensory processing, attention, and memory, the mechanisms by which cholinergic signaling regulates cognitive processes remain elusive. In this study, we recorded spiking and local field potential data simultaneously from several locations in the BF, and sites in the orbitofrontal and visual cortex in transgenic ChAT-Cre rats performing a visual discrimination task. We observed distinct differences in the fine spatial distributions of gamma coherence values between specific basalo-cortical and cortico-cortical sites that shifted across task phases. Additionally, cholinergic firing induced spatial changes in cortical gamma power, and optogenetic activation of BF increased coherence between specific cortico-cortical sites, suggesting that the cholinergic system contributes to selective modulation of cortico-cortical circuits. Furthermore, the results suggest that cells in specific BF locations are dynamically recruited across behavioral epochs to coordinate interregional cortical processes underlying cognition.

Training concept of integrative medicine in Hungary based on international models / Az integratív medicina képzésének hazai koncepciója nemzetközi minták alapján.

Integrative medicine is a new approach in the 21st century healthcare system, which integrates conventional medicine and evidence-based, safe and efficient complementary therapies into a unified biomedicine. Medical doctors and complementary therapists work together in partnership with patients to help them recover and live a whole life. Equally important is the maintenance and enhancement of health and well-being in which therapists become role-models. In this article, the authors introduce a proposal for the concept and major elements of a two-year integrative medicine postgraduate training for specialist doctors in Hungary and summarize international progress in the field. Orv Hetil. 2020; 161(27): 1122-1130.

Clustering of large cell populations: method and application to the basal forebrain cholinergic system.

Functionally related groups of neurons spatially cluster together in the brain. To detect groups of functionally related neurons from 3D histological data, we developed an objective clustering method that provides a description of detected cell clusters that is quantitative and amenable to visual exploration. This method is based on bubble clustering (Gupta and Ghosh, 2008). Our implementation consists of three steps: (i) an initial data exploration for scanning the clustering parameter space; (ii) determination of the optimal clustering parameters; and (iii) final clustering. We designed this algorithm to flexibly detect clusters without assumptions about the underlying cell distribution within a cluster or the number and sizes of clusters. We implemented the clustering function as an integral part of the neuroanatomical data visualization software Virtual RatBrain (http://www.virtualratbrain.org). We applied this algorithm to the basal forebrain cholinergic system, which consists of a diffuse but inhomogeneous population of neurons (Zaborszky, 1992). With this clustering method, we confirmed the inhomogeneity in this system, defined cell clusters, quantified and localized them, and determined the cell density within clusters. Furthermore, by applying the clustering method to multiple specimens from both rat and monkey, we found that cholinergic clusters display remarkable cross-species preservation of cell density within clusters. This method is efficient not only for clustering cell body distributions but may also be used to study other distributed neuronal structural elements, including synapses, receptors, dendritic spines and molecular markers.