Biology subjects

Ulyanova, A. V.

Publications and source records attributed to Ulyanova, A. V..

6 recordsLinked to original sources

bioRxiv2026

Increased CD3 Immunoreactive Cells Persist Chronically in the Brain Parenchyma in Association with Focal Cortical Contusion following Experimental TBI

While a history of TBI is associated with an increased risk of neurodegenerative disease, associated mechanisms remain largely unknown. Neuroinflammation is commonly implicated as playing a role in progressive neurodegeneration in general, yet little is known about the adaptive response of neuroinflammation in TBI or how it may contribute to progressive pathologies. To parse out components of the adaptive response, we assessed for intraparenchymal T-cell infiltration in two different translational large animal (swine) models of TBI, inertial injury and focal contusion. We characterized the extent and distribution of T cells post-injury and their association with blood-brain barrier disruption and axonal pathology. T-cell infiltration following focal TBI followed a spatiotemporal progression from gray matter at 72 hours to both gray and white matter at 6 months post-injury, consistent with recruitment into the parenchyma and then white matter. Inertial injury did not lead to substantial T-cell infiltration despite BBB breakdown and axonal pathology. We did not find a spatial correlation between blood-brain barrier breakdown or axonal pathology and T-cell infiltration in focal TBI. These data suggest that there is an active adaptive response to TBI, particularly in tissue proximal to contusions. A large animal model that reproducibly demonstrates chronic T-cell infiltration may allow for examination of the downstream effects of the adaptive response to TBI, and whether targeting this adaptive response may reduce chronic inflammation and improve recovery.

neuroscience↗

bioRxiv2024

Disrupted Hippocampal Theta-Gamma Coupling and Spike-Field Coherence Following Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) often results in persistent learning and memory deficits, likely due to disrupted hippocampal circuitry underlying these processes. Precise temporal control of hippocampal neuronal activity is thought to be important for memory encoding and retrieval and is supported by oscillations that dynamically organize single unit firing. Using high-density laminar electrophysiology, we found a loss of oscillatory power across CA1 lamina, with a profound, layer-specific reduction in theta-gamma phase amplitude coupling in injured rats. Interneurons from injured animals were less strongly entrained to theta and gamma oscillations, but both interneurons and pyramidal cells from injured animals became more strongly entrained to theta during periods of high theta power. During quiet immobility, sharp-wave ripple amplitudes were lower in injured animals compared to shams. These results reveal physiological deficits across brain states that may contribute to TBI-associated learning and memory impairments and elucidate potential targets for future neuromodulation therapies.

neuroscience↗

bioRxiv2022

Hippocampal Interneuronal Dysfunction and Hyperexcitability in Porcine Model of Concussion

Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40 - 80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI.

neuroscience↗

bioRxiv2018

Multichannel Silicon Probes for Laminar Cortical and Hippocampal Recordings in Large Animals.

Decoding laminar information across deep brain structures and cortical regions is necessary in order to understand the spatiotemporal ensembles that represent cognition and memory. Large animal models are essential for translational research due to their gyrencephalic neuroanatomy and significant white matter composition. One of the major obstacles to applying the approaches currently utilized in lower order animals are technical limitations in silicon probes, specifically a lack of long-length probes with appropriate stiffness to penetrate to deeper structures with minimal damage to the neural interface. We tested various solutions and designs of multichannel silicon probes developed for large animal electrophysiology by recording neurophysiological signals from deep laminar structures in an acute preparation and in chronically implanted awake behaving Yucatan pigs. Electrophysiological parameters of single units and local field potentials were analyzed to evaluate performance over time of given silicon probes in chronic implantations. The cross-sectional area of silicon probes was found to be a crucial determinant of silicon probes single unit performance over time, potentially due to reduction of damage to the neural interface. EDGE-style probes had the highest yields during intra-hippocampal recordings in pigs, making them the most suitable for chronic implantations and awake behavioral experimentation. Novel CAMB 64-channel EDGE-style probes with linear and poly-2 site arrangement tested acutely had optimal single unit separation and a denser sampling of the laminar structure, identifying them as potential candidates for chronic implantations with less cortical damage above the active portion of the probe. This study provides an analysis of multichannel silicon probes designed for large animal laminar electrophysiology of deep brain structures, and suggests that current designs are reaching the physical thresholds necessary for long-term (~ 1 month) recordings from laminar deep structures with single-unit resolution.

neuroscience↗

bioRxiv2017

Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles

Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4th order arterioles in mouse skeletal muscle. Currents through L-type Ca2+ channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca2+-free bathing solution or by addition of L-type Ca2+ channel blocker nifedipine (10 M). Instead, Na+ channel blocker tetrodotoxin (TTX, 1 M) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca2+ in the bath. The magnitude of TTX-sensitive currents recorded with 140 mM Na+ was about 20 pA/pF. TTX-sensitive currents decreased five-fold when Ca2+ increased from 2 to 10 mM. The currents reduced three-fold in the presence of 10 mM caffeine, but remained unaltered by 1 mM of isobutylmethylxanthine (IBMX). In addition to L-type Ca2+ currents (15 pA/pF in 20 mM Ca2+), we also found Ca2+ currents that are resistant to 10 M nifedipine (5 pA/pF in 20 mM Ca2+). Based on their biophysical properties, these Ca2+ currents are likely to be through voltage-gated T-type Ca2+ channels. Our results suggest that Na+ and at least two types (T- and L-) of Ca2+ voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles. Voltage-gated Na+ channels appear to be under a tight control by Ca2+ signaling.

physiology↗

bioRxiv2017

Electrophysiological Signature Reveals Laminar Structure of the Porcine Hippocampus

The hippocampus is integral to working and episodic memory, and is a central region of interest in diseases affecting these processes. Pig models are widely used in translational research, and may provide an excellent bridge between rodents and non-human primates for CNS disease models due to their gyrencephalic neuroanatomy and significant white matter composition. However, the laminar structure of the pig hippocampus has not been well characterized. Therefore, we histologically characterized the dorsal hippocampus of Yucatan miniature pigs and quantified the cytoarchitecture of the hippocampal layers. We then utilized stereotaxis combined with single unit electrophysiological mapping to precisely place multichannel laminar silicon probes into the dorsal hippocampus without the need for image guidance. We used in vivo electrophysiological recordings of simultaneous laminar field potentials and single unit activity in multiple layers of the dorsal hippocampus to physiologically identify and quantify these layers under anesthesia. Consistent with previous reports, we found the porcine hippocampus to have the expected archicortical laminar structure with some anatomical and histological features comparable to the rodent and others to the primate hippocampus. Importantly, we found these distinct features to be reflected in the laminar electrophysiology. This characterization, as well as our electrophysiology-based methodology targeting the porcine hippocampal lamina combined with high channel count silicon probes will allow for analysis of spike-field interactions during normal and disease states in both anesthetized and future awake behaving neurophysiology in this large animal.\n\nSignificance StatementThe hippocampus is central to working and episodic memory and is critically affected by diverse disease processes. In order to investigate hippocampal electrophysiology in translational large animal models, we developed an imaging-free stereotaxis and intraoperative electrophysiology methodology with custom silicon probes to precisely localize probe placement within the hippocampal laminar structure. We report for the first time the profile of single units and local field potentials in the pig dorsal hippocampus and relate them to a histological description. This characterization forms the basis for accessible translational pig models to study diseases of the central nervous system affecting hippocampal circuitry in the large animal gyrencephalic brain, as well as the groundwork for potential awake behaving neurophysiology of the porcine hippocampus.\n\nFunding SourcesThe Department of Veterans Affairs, IK2-RX001479, I01-RX001097. The National Institutes of Health, NINDS R01-NS-101108-01, T32-NS043126. CURE Foundation, Taking Flight Award. DoD ERP CDMRP, W81XWH-16-1-0675.

neuroscience↗