BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors.

Effects of Ketamine on Frontoparietal Interactions in a Rule-Based Antisaccade Task in Macaque Monkeys.

Cognitive control is engaged by working memory processes and high-demand situations like antisaccade, where one must suppress a prepotent response. While it is known to be supported by the frontoparietal control network, how intra- and interareal dynamics contribute to cognitive control processes remains unclear. -Methyl-d-aspartate glutamate receptors (NMDARs) play a key role in prefrontal dynamics that support cognitive control.

Small data methods in omics: the power of one.

Over the last decade, biology has begun utilizing 'big data' approaches, resulting in large, comprehensive atlases in modalities ranging from transcriptomics to neural connectomics. However, these approaches must be complemented and integrated with 'small data' approaches to efficiently utilize data from individual labs. Integration of smaller datasets with major reference atlases is critical to provide context to individual experiments, and approaches toward integration of large and small data have been a major focus in many fields in recent years.

Single-cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Trem2 Alzheimer's risk gene mutation.

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer's Disease. In this study, we analyze the impact of the Trem2 mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2, 5xFAD and Trem2; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression.

ULV: A robust statistical method for clustered data, with applications to multi-subject, single-cell omics data.

Molecular and genomic technological advancements have greatly enhanced our understanding of biological processes by allowing us to quantify key biological variables such as gene expression, protein levels, and microbiome compositions. These breakthroughs have enabled us to achieve increasingly higher levels of resolution in our measurements, exemplified by our ability to comprehensively profile biological information at the single-cell level. However, the analysis of such data faces several critical challenges: limited number of individuals, non-normality, potential dropouts, outliers, and repeated measurements from the same individual.

Single-cell spatial transcriptomics reveals a dystrophic trajectory following a developmental bifurcation of myoblast cell fates in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is linked to abnormal derepression of the transcription activator DUX4. This effect is localized to a low percentage of cells, requiring single-cell analysis. However, single-cell/nucleus RNA-seq cannot fully capture the transcriptome of multinucleated large myotubes.

Laminar Dynamics of Target Selection in the Posterior Parietal Cortex of the Common Marmoset.

The lateral intraparietal area (LIP) plays a crucial role in target selection and attention in primates, but the laminar microcircuitry of this region is largely unknown. To address this, we used ultra-high density laminar electrophysiology with Neuropixels probes to record neural activity in the posterior parietal cortex (PPC) of two adult marmosets while they performed a simple visual target selection task. Our results reveal neural correlates of visual target selection in the marmoset, similar to those observed in macaques and humans, with distinct timing and profiles of activity across cell types and cortical layers.

A ubiquitous spectrolaminar motif of local field potential power across the primate cortex.

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs).

Single cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Alzheimer's risk gene mutation.

Introduction: The R47H missense mutation of the TREM2 gene is a strong risk factor for development of Alzheimer's Disease. We investigate cell-type-specific spatial transcriptomic changes induced by the mutation to determine the impacts of this mutation on transcriptional dysregulation.

Methods: We profiled 15 mouse brain sections consisting of wild-type, , 5xFAD and ; 5xFAD genotypes using MERFISH spatial transcriptomics.

Anatomical and molecular characterization of parvalbumin-cholecystokinin co-expressing inhibitory interneurons: implications for neuropsychiatric conditions.

Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly; between 40 and 56% of PV+ interneurons in mouse hippocampal CA1 express CCK.

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat.

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome.

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat.

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome.

Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease.

A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice.

Delay-related activity in marmoset prefrontal cortex.

Persistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms; however, a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations.

Simultaneous functional MRI of two awake marmosets.

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level.

Interspecies activation correlations reveal functional correspondences between marmoset and human brain areas.

The common marmoset has enormous promise as a nonhuman primate model of human brain functions. While resting-state functional MRI (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. This limitation can be overcome by movie-driven fMRI (md-fMRI), which has become a popular tool for noninvasively mapping the neural patterns generated by rich and naturalistic stimulation.

Ketamine disrupts gaze patterns during face viewing in the common marmoset.

Faces are stimuli of critical importance for primates. The common marmoset () is a promising model for investigations of face processing, as this species possesses oculomotor and face-processing networks resembling those of macaques and humans. Face processing is often disrupted in neuropsychiatric conditions such as schizophrenia (SZ), and thus, it is important to recapitulate underlying circuitry dysfunction preclinically.

A Novel Three-Choice Touchscreen Task to Examine Spatial Attention and Orienting Responses in Rodents.

Mammalian orienting behavior consists of coordinated movements of the eyes, head, pinnae, vibrissae, or body to attend to an external stimulus. The present study aimed to develop a novel operant task using a touch-screen system to measure spatial attention. In this task, rats were trained to nose-poke a light stimulus presented in one of three locations.

Structural alterations in cortical and thalamocortical white matter tracts after recovery from prefrontal cortex lesions in macaques.

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional brain changes relate with the underlying structural white matter tracts. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with changes in white matter microstructure across large-scale frontoparietal cortical and thalamocortical networks.

An unusual case of high-voltage electrical injury involving fractal wood burning.

A 26-year-old female was brought to the emergency department after an apparent electrocution. She was unresponsive, pulseless, and found to be in ventricular fibrillation upon arrival. The patient achieved return of spontaneous circulation after defibrillation.

Face selective patches in marmoset frontal cortex.

In humans and macaque monkeys, socially relevant face processing is accomplished via a distributed functional network that includes specialized patches in frontal cortex. It is unclear whether a similar network exists in New World primates, who diverged ~35 million years from Old World primates. The common marmoset is a New World primate species ideally placed to address this question given their complex social repertoire.