Cortical cell assemblies and their underlying connectivity: An in silico study.

Recent developments in experimental techniques have enabled simultaneous recordings from thousands of neurons, enabling the study of functional cell assemblies. However, determining the patterns of synaptic connectivity giving rise to these assemblies remains challenging. To address this, we developed a complementary, simulation-based approach, using a detailed, large-scale cortical network model. Using a combination of established methods we detected functional cell assemblies from the stimulus-evoked spiking activity of 186,665 neurons. We studied how the structure of synaptic connectivity underlies assembly composition, quantifying the effects of thalamic innervation, recurrent connectivity, and the spatial arrangement of synapses on dendrites. We determined that these features reduce up to 30%, 22%, and 10% of the uncertainty of a neuron belonging to an assembly. The detected assemblies were activated in a stimulus-specific sequence and were grouped based on their position in the sequence. We found that the different groups were affected to different degrees by the structural features we considered. Additionally, connectivity was more predictive of assembly membership if its direction aligned with the temporal order of assembly activation, if it originated from strongly interconnected populations, and if synapses clustered on dendritic branches. In summary, reversing Hebb's postulate, we showed how cells that are wired together, fire together, quantifying how connectivity patterns interact to shape the emergence of assemblies. This includes a qualitative aspect of connectivity: not just the amount, but also the local structure matters; from the subcellular level in the form of dendritic clustering to the presence of specific network motifs.

Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using 99mTc-GA-5 as a Potential In Vivo Tracer.

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

High-resolution Micro-CT Myelography to Assess Spinal Subarachnoid Space Changes After Spinal Cord Injury in Rats.

BACKGROUND AND PURPOSE: The spinal subarachnoid space (SSAS) is vital for neurologic function. Although SSAS alterations are known to occur after spinal cord injury (SCI), there is a lack of high-resolution imaging studies of the SSAS after SCI in rodents. Therefore, the aim here was to assess changes in the SSAS of rats subjected to graded SCI, using high-resolution micro-CT myelography. METHODS: Long-Evans adult rats were subjected to mild or severe spinal cord contusion at T9. Imaging studies of SSAS features were carried out in injured rats at acute (day 1) and subacute (day 15) stages postinjury, as well as in control rats, using high-resolution micro-CT myelography with a contrast-enhanced digital subtraction protocol. We studied a total of 33 rats randomly allocated into five experimental groups. Micro-CT myelograms were assessed by expert observers using both qualitative and quantitative criteria. RESULTS: Qualitative and quantitative analyses showed that SCI induces changes in the SSAS that vary as a function of both injury severity and time elapsed after injury. SSAS blockage was the main alteration detected. Moreover, the method used here allowed fine details to be observed in small animals, such as variations in the preferential pathways for contrast medium flow, neuroimaging nerve root enhancement, and leakage of contrast medium due to tearing of the dural sac. CONCLUSION: Micro-CT myelography provides high-resolution images of changes in the SSAS after SCI in rats and is a useful tool for further experimental studies involving rat SCI in vivo.

Micro-CT myelography using contrast-enhanced digital subtraction: feasibility and initial results in healthy rats.

PURPOSE: The spinal subarachnoid space (SSAS) is vital for neural performance. Although models of spinal diseases and trauma are used frequently, no methods exist to obtain high-resolution myelograms in rodents. Thereby, our aim was to explore the feasibility of obtaining high-resolution micro-CT myelograms of rats by contrast-enhanced dual-energy (DE) and single-energy (SE) digital subtraction. METHODS: Micro-CT contrast-enhanced DE and SE imaging protocols were implemented with live adult rats (total of 18 animals). For each protocol, contrast agents based on iodine (Iomeron® 400 and Fenestra® VC) and gold nanoparticles (AuroVist™ 15 nm) were tested. For DE, images at low- and high-energy settings were acquired after contrast injection; for SE, one image was acquired before and the other after contrast injection. Post-processing consisted of region of interest selection, image registration, weighted subtraction, and longitudinal alignment. RESULTS: High-resolution myelograms were obtained with contrast-enhanced digital subtraction protocols. After qualitative and quantitative (contrast-to-noise ratio) analyses, we found that the SE acquisition protocol with Iomeron® 400 provides the best images. 3D contour renderings allowed visualization of SSAS and identification of some anatomical structures within it. CONCLUSION: This in vivo study shows the potential of SE contrast-enhanced myelography for imaging SSAS in rat. This approach yields high-resolution 3D images without interference from adjacent anatomical structures, providing an innovative tool for further assessment of studies involving rat SSAS.