Integrated resource for functional and structural connectivity of the marmoset brain

The comprehensive integration of structural and functional connectivity data is required for the accurate modeling of brain functions. While resources for studying structural connectivity of non-human primate marmoset brains already exist, their integration with functional connectivity data has remained unavailable. Therefore, we present a comprehensive resource for marmoset brain mapping, which integrates the largest awake resting-state fMRI dataset to date (39 marmosets, 709 runs, and 12053 mins), cellular-level neuronal-tracing dataset (52 marmosets and 143 injections), and multi-resolution diffusion MRI dataset. The combination of these data into the same MRI space allowed us to 1). map the fine-detailed functional networks and cortical parcellations; 2). develop a deep-learning-based parcellation generator to preserve the topographical organization of functional connectivity and reflect individual variabilities; 3). investigate the structural basis underlying functional connectivity by computational modeling. Our resource will broadly model the marmoset brain architecture and facilitate future comparative and translational studies of primate brains.

A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system

We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion - the right atrial ganglionic plexus (RAGP) that is a critical mediator of vagal control of the sinoatrial node (SAN) activity. We developed a 3D representation of RAGP with extensive mapping of neurons and used neuronal tracing to identify the spatial distribution of the subset of neurons that project to the SAN. RNAseq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to CNS neuronal subtypes. High-throughput qPCR of hundreds of laser capture microdissected single neurons led to a surprising finding that cholinergic and catecholaminergic neuronal markers Th and Chat were correlated, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. Interestingly, no single gene or module was an exclusive marker of RAGP neuronal connectivity to SAN. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP, informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.

A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system

We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion - the right atrial ganglionic plexus (RAGP) that is a critical mediator of vagal control of the sinoatrial node (SAN) activity. We developed a 3D representation of RAGP with extensive mapping of neurons and used neuronal tracing to identify the spatial distribution of the subset of neurons that project to the SAN. RNAseq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to CNS neuronal subtypes. High-throughput qPCR of hundreds of laser capture microdissected single neurons led to a surprising finding that cholinergic and catecholaminergic neuronal markers Th and Chat were correlated, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. Interestingly, no single gene or module was an exclusive marker of RAGP neuronal connectivity to SAN. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP, informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.

PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.

Legacy of Prof. Juraj Korpáš: International Impact of Slovak School of Experimental Respirology

Human health is the main role of medical research. Scientists were always intrigued by disease prevention, their diagnostics and proper treatment. In fact, research in medicine is always directed towards the improvement of the health care and improvement of the quality of life of the target population. Nowadays, physiological research, which is the base stone for clinical research, progresses fast forward, providing new information about body functions in health and diseases. This obvious progress is associated with modern methods, such as neuronal tracing, patch-clamp methods, electrophysiology, molecular biology and many more, which supported by comprehensive information technology guarantees high quality and complex data. Our younger colleagues, young scientists, post-docs or PhD students are well-trained and qualified in utilizing these new methods.

A newly identified trigeminal brain pathway in a night-migratory bird could be dedicated to transmitting magnetic map information

Night-migratory songbirds can use geomagnetic information to navigate over thousands of kilometres with great precision. A crucial part of the magnetic ‘map’ information used by night-migratory songbirds is conveyed via the ophthalmic branches of the trigeminal nerves to the trigeminal brainstem complex, where magnetic-driven neuronal activation has been observed. However, it is not known how this information reaches the forebrain for further processing. Here, we show that the magnetically activated region in the trigeminal brainstem of migratory Eurasian blackcaps ( Sylvia atricapilla ) represents a morphologically distinctive neuronal population with an exclusive and previously undescribed projection to the telencephalic frontal nidopallium. This projection is clearly different from the known trigeminal somatosensory pathway that we also confirmed both by neuronal tracing and by a thorough morphometric analysis of projecting neurons. The new pathway we identified here represents part of a brain circuit that—based on the known nidopallial connectivities in birds—could potentially transmit magnetic ‘map’ information to key multisensory integration centres in the brain known to be critically involved in spatial memory formation, cognition and/or controlling executive behaviour, such as navigation, in birds.

NADPH diaphorase neuronal dystrophy in gracile nucleus, cuneatus nucleus and spinal trigeminal nucleus in aged rat

NADPH-diaphorase (N-d) activity is commonly used to identify NOS-ergic neurons. In our previous study, N-d positive neuritic dystrophy and spheroid termed aging-related N-d Body is discovered in the lumbosacral spinal cord in the normal aging rats. Histological studies also reveal that N-d positive neurodegenerative changes occur in the gracile nucleus. We re-examined N-d activity in gracile nucleus in aged rat. We found N-d positive neuritic dystrophy and spheroid also occurred in the cuneatus nucleus and spinal trigeminal nucleus. Besides regular coronal section, longitudinal oriented dystrophic neurites were detected in the sagittal and horizontal section in gracile nucleus and dorsal column. We fziurther examined the medullary oblongata with regular classical histology including Golgi staining, immunocytochemistry of NOS and phosphorylated tau protein, neuronal tracing method with wheat germ agglutinin conjugated alexa-fluor-488 through sciatic nerve, and spinal cord transection at thoracic level. Most of N-d positive neuritic dystrophy and spheroid did not showed colocalization with NOS or phosphorylated tau protein. Neuronal tracing and spinal cord transection revealed that N-d dystrophic neurites in gracile nucleus originated from terminal of sensory projection from spinal cord and peripheral somatic input. The results suggested that aging-related N-d dystrophy in the gracile nucleus was unique morphological feature. In conclusion, it was postulated that the N-d dystrophy as a morphological marker of aging degenerative damage in normal aged organisms.

Sortase-Modified Cholera Toxoids Show Specific Golgi Localization

Cholera toxoid is an established tool for use in cellular tracing in neuroscience and cell biology. We use a sortase-labelling approach to generate site-specifically <i>N</i>-terminally modified variants of both the A2-B₅ heterohexamer and B₅ pentamer forms of the toxoid. Both forms of the toxoid are endocytosed by GM1-positive mammalian cells, and while the heterohexameric toxoid was principally localized in the ER, the B₅ pentamer showed an unexpected localization in the <i>medial/trans</i> Golgi. This study suggests a future role for specifically-labelled cholera toxoids in live-cell imaging beyond their current applications in neuronal tracing and labelling of lipid-rafts in fixed cells.