scholarly journals Multiplex, translaminar imaging in the spinal cord of behaving mice

2021 ◽  
Author(s):  
Pavel Shekhtmeyster ◽  
Erin M. Carey ◽  
Daniela Duarte ◽  
Alexander Ngo ◽  
Grace Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Imaging Techniques ◽  
Activity Patterns ◽  
Cell Types ◽  
Integrated System ◽  
Sensorimotor Processing ◽  
Activity Measurements ◽  
Multiple Challenges ◽  
Evoked Activity ◽  
Working Distance

While the spinal cord is known to play critical roles in sensorimotor processing, including pain-related signaling, corresponding activity patterns in genetically defined cell types across spinal laminae have remained elusive. Calcium imaging has enabled cellular activity measurements in behaving rodents but is currently limited to superficial regions. Using chronically implanted microprisms, we imaged sensory and motor evoked activity in regions and at speeds inaccessible by other high-resolution imaging techniques. To enable translaminar imaging in freely behaving animals through implanted microprisms, we additionally developed wearable microscopes with custom-compound microlenses. This new integrated system addresses multiple challenges of previous wearable microscopes, including their limited working distance, resolution, contrast, and achromatic range. The combination of these innovations allowed us to uncover that dorsal horn astrocytes in behaving mice show somatosensory program-dependent and lamina-specific calcium excitation. Additionally, we show that tachykinin precursor 1 (Tac1)-expressing neurons exhibit upper laminae-restricted activity to acute mechanical pain but not locomotion.

scholarly journals Trans-segmental imaging in the spinal cord of behaving mice

2021 ◽  
Author(s):  
Pavel Shekhtmeyster ◽  
Daniela Duarte ◽  
Erin M. Carey ◽  
Alexander Ngo ◽  
Grace Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Activity Patterns ◽  
Field Of View ◽  
Lateral Resolution ◽  
Mechanical Stimuli ◽  
Spinal Segments ◽  
Working Distance

Spinal cord circuits play crucial roles in transmitting and gating cutaneous somatosensory modalities, such as pain, but the underlying activity patterns within and across spinal segments in behaving mice have remained elusive. To enable such measurements, we developed a wearable widefield macroscope with a 7.9 mm2 field of view, subcellular lateral resolution, 2.7 mm working distance, and <10 g overall weight. We show that highly localized painful mechanical stimuli evoke widespread, coordinated astrocyte excitation across multiple spinal segments.

scholarly journals The search for a hippocampal engram

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130161 ◽  
Author(s):  
Mark Mayford
Keyword(s):  
Declarative Memory ◽  
Imaging Techniques ◽  
Activity Patterns ◽  
Neural Ensembles ◽  
Complex Information ◽  
Specific Memory ◽  
Complex Forms ◽  
Evoked Activity ◽  
Sensory Evoked

Understanding the molecular and cellular changes that underlie memory, the engram, requires the identification, isolation and manipulation of the neurons involved. This presents a major difficulty for complex forms of memory, for example hippocampus-dependent declarative memory, where the participating neurons are likely to be sparse, anatomically distributed and unique to each individual brain and learning event. In this paper, I discuss several new approaches to this problem. In vivo calcium imaging techniques provide a means of assessing the activity patterns of large numbers of neurons over long periods of time with precise anatomical identification. This provides important insight into how the brain represents complex information and how this is altered with learning. The development of techniques for the genetic modification of neural ensembles based on their natural, sensory-evoked, activity along with optogenetics allows direct tests of the coding function of these ensembles. These approaches provide a new methodological framework in which to examine the mechanisms of complex forms of learning at the level of the neurons involved in a specific memory.

scholarly journals Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

scholarly journals Planet of the AAVs: The Spinal Cord Injury Episode

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 613
Author(s):  
Katerina Stepankova ◽  
Pavla Jendelova ◽  
Lucia Machova Urdzikova
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Cell Types ◽  
Specific Cell ◽  
Adeno Associated Virus ◽  
Adequate Treatment ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Transgene Delivery

The spinal cord injury (SCI) is a medical and life-disrupting condition with devastating consequences for the physical, social, and professional welfare of patients, and there is no adequate treatment for it. At the same time, gene therapy has been studied as a promising approach for the treatment of neurological and neurodegenerative disorders by delivering remedial genes to the central nervous system (CNS), of which the spinal cord is a part. For gene therapy, multiple vectors have been introduced, including integrating lentiviral vectors and non-integrating adeno-associated virus (AAV) vectors. AAV vectors are a promising system for transgene delivery into the CNS due to their safety profile as well as long-term gene expression. Gene therapy mediated by AAV vectors shows potential for treating SCI by delivering certain genetic information to specific cell types. This review has focused on a potential treatment of SCI by gene therapy using AAV vectors.

scholarly journals Nasal Chemosensory-Stimulation Evoked Activity Patterns in the Rat Trigeminal Ganglion Visualized by In Vivo Voltage-Sensitive Dye Imaging

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26158 ◽  
Author(s):  
Markus Rothermel ◽  
Benedict Shien Wei Ng ◽  
Agnieszka Grabska-Barwińska ◽  
Hanns Hatt ◽  
Dirk Jancke
Keyword(s):  
Trigeminal Ganglion ◽  
Activity Patterns ◽  
Voltage Sensitive Dye ◽  
Evoked Activity ◽  
Voltage Sensitive Dye Imaging

Spinally Administered Epinephrine Suppresses Noxiously Evoked Activity of WDR Neurons in the Dorsal Horn of the Spinal Cord

1984 ◽  
Vol 60 (4) ◽  
pp. 269-275 ◽  
Author(s):  
J. G. Collins ◽  
L. M. Kitahata ◽  
M. Matsumoto ◽  
E. Homma ◽  
M. Suzukawa
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Evoked Activity ◽  
Wdr Neurons

scholarly journals Understanding axial progenitor biology in vivo and in vitro

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev180612
Author(s):  
Filip J. Wymeersch ◽  
Valerie Wilson ◽  
Anestis Tsakiridis
Keyword(s):  
Spinal Cord ◽  
Vertebral Column ◽  
Cell Types ◽  
Disease Modelling ◽  
Recent Developments ◽  
The Common ◽  
Key Features ◽  
Trunk Musculature

ABSTRACTThe generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the in vitro production of axial progenitors and their potential implications in disease modelling and regenerative medicine.

scholarly journals Renal cell markers: lighthouses for managing renal diseases

2021 ◽  
Author(s):  
Shivangi Agarwal ◽  
Yashwanth R Sudhini ◽  
Onur K Polat ◽  
Jochen Reiser ◽  
Mehmet Mete Altintas
Keyword(s):  
High Efficiency ◽  
Imaging Techniques ◽  
Unmet Need ◽  
Cell Types ◽  
Whole Body ◽  
Renal Diseases ◽  
Cell Type ◽  
Cell Markers ◽  
Urine Production

Kidneys, one of the vital organs in our body, are responsible for maintaining whole-body homeostasis. The complexity of renal function (e.g., filtration, reabsorption, fluid and electrolyte regulation, urine production) demands diversity not only at the level of cell types but also in their overall distribution and structural framework within the kidney. To gain an in-depth molecular-level understanding of the renal system, it is imperative to discern the components of kidney and the types of cells residing in each of the sub-regions. Recent developments in labeling, tracing, and imaging techniques enabled us to mark, monitor and identify these cells in vivo with high efficiency in a minimally invasive manner. In this review, we have summarized different cell types, specific markers that are uniquely associated with those cell types, and their distribution in kidney, which altogether make kidneys so special and different. Cellular sorting based on the presence of certain proteins on the cell surface allowed for assignment of multiple markers for each cell type. However, different studies using different techniques have found contradictions in the cell-type specific markers. Thus, the term "cell marker" might be imprecise and sub-optimal, leading to uncertainty when interpreting the data. Therefore, we strongly believe that there is an unmet need to define the best cell markers for a cell type. Although, the compendium of renal-selective marker proteins presented in this review is a resource that may be useful to the researchers, we acknowledge that the list may not be necessarily exhaustive.

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