Biology subjects

Chinta, S.

Publications and source records attributed to Chinta, S..

5 recordsLinked to original sources

bioRxiv2024

Pre-treatments of Ex vivo Vascularized Composite Allografts: A Scoping Review

PURPOSEThe various physiological profiles comprising vascularized composite allografts (VCAs) pose unique challenges to preservation. Minimizing ischemia, reperfusion injury, and rejection remains a primary focus of graft pre-treatments (PTs). Currently, the gold standard PT consists of flushing the graft and placing it in static cold storage in the University of Wisconsin solution. With this method, graft viability is limited to four to six hours. Prolonging this time limit will increase donor allocation radius, access to care, and positive patient outcomes. We aimed to evaluate novel PTs that could potentially enhance and lengthen VCA viability. METHODSFollowing PRISMA guidelines, we conducted a comprehensive literature search of Embase, Cochrane, and PubMed. Studies had to be published prior to June 15, 2022. PTs had to target cell physiology, rather than immunogenicity. We extracted data including study design, PT details, evaluation metrics, and outcomes. RESULTSWe identified thirteen studies, categorized into three groups: solution-based alterations to the gold standard, ex vivo perfusion, and other novel techniques. The incorporation of hydrogen sulfide and Perfadex as solutions in the gold standard protocol demonstrated a six-day delay in rejection and limited reperfusion injury markers, respectively. In one ex vivo perfusion study, after 24 hours of PT and 12 hours post-transplant, VCA muscle contractility remained close to normal. The gold standard PT did not demonstrate the same success. However, graft weight gain, up to 50% of baseline among the articles reviewed, is a prominent side effect of perfusion. Another technique, cryopreservation, displayed 90% graft failure by venous thrombosis, despite high free graft viability following two weeks of storage. CONCLUSIONSThis study of pre-treatment modalities found a variety of encouraging preservation techniques for grafts with high levels of tissue diversity. Ex vivo perfusion dominated PT innovation with promising results in preserving the viability and functionality of muscle, which is central to the restoration of movement. Future studies are necessary to evaluate long-term graft outcomes and to optimize PT protocols for extended preservation times to ensure clinical relevance.

systems biology↗

bioRxiv2024

Stimulus selection drives value-modulated somatosensory processing in superior colliculus

A fundamental trait of intelligent behavior is the ability to respond selectively to stimuli with higher value. Where along the somatosensory hierarchy does information transition from a map of stimulus location to a map of stimulus value? To address this question, we recorded single-unit activity from populations of neurons in somatosensory cortex (S1) and midbrain superior colliculus (SC) in mice conditioned to respond to a positive-valued whisker stimulus and withhold responses using an adjacent, negative-valued whisker stimulus. The stimulus preference of the S1 population was equally weighted towards either whisker, in line with a somatotopic map. Surprisingly, we discovered a large population of SC neurons that were disproportionately biased towards the positive stimulus. This disproportionate bias was controlled by spike facilitation for the positive stimulus and spike suppression for the negative stimulus in single neurons. Removing the opportunity for mice to select the positive stimulus reduced stimulus bias in SC but not S1, suggesting that sensory processing in SC neurons was partially controlled by movement preparation. Similarly, the spontaneous firing rates of SC but not S1 neurons accurately predicted reaction times, suggesting that SC neurons play a persistent role in perceptual decision-making. Taken together, these data indicate that the somatotopic map in S1 is transformed into a value-based map in SC that encodes stimulus priority.

neuroscience↗

bioRxiv2024

Highly synchronized inhibition from Purkinje cells entrains cerebellar output in zebrafish

Cerebellar function, known to be important for motor learning and motor coordination, is mediated by efferent neurons that project to diverse motor areas. To understand cerebellar function, it is imperative to study how these efferent neurons integrate inputs from the principal neurons of the cerebellar cortex, the inhibitory Purkinje neurons (PNs). In zebrafish, PNs are bistable and we show here that bistability influences spike synchrony among PNs. Bistability also alters spike correlation with motor bouts. We asked how PN population synchrony influences Eurydendroid cells (ECs), which are postsynaptic targets of PNs and are the cerebellar efferent cells in zebrafish. Using optogenetics, we artificially modulated population synchrony of PNs over millisecond time scales and showed that under conditions of high synchrony, EC firing is briefly suppressed and entrained by PN spiking. However, the magnitude of such modulation is relatively small and indicates a strong combined influence of other synaptic inputs on EC spiking. Key PointsO_LICerebellar Purkinje neurons (PN) in larval zebrafish alter simple spike correlations with each other based on cellular state. C_LIO_LIThey also alter simple spike correlations with motor bouts as a function of state. C_LIO_LIWe altered PN population synchrony in a graded manner using optogenetics. C_LIO_LIPN targets are cerebellar efferent neurons, which in teleosts are called eurydendroid cells. C_LIO_LIWhen PN population is firing with high synchrony, eurydendroid cells are entrained better than when the PN input is asynchronous. C_LIO_LIThis can explain how PNs use bistability to modulate their influence on cerebellar output and ultimately, motor behavior. C_LI

neuroscience↗

bioRxiv2024

Internal monitoring of whisking and locomotion in the superior colliculus

To localize objects using active touch, our brain must merge its map of the body surface with an ongoing representation of self-motion. While such computations are often ascribed to the cerebral cortex, we examined the midbrain superior colliculus (SC), due to its close relationship with the sensory periphery as well as higher, motor-related brain regions. We discovered that active whisking kinematics and locomotion speed accurately predict the firing rate of mouse SC neurons. Kinematic features occurring either in the past, present, or future best predicted spiking, indicating that the SC population continuously estimates the trajectory of self-motion. Half of all self-motion encoding neurons displayed a touch response as an object entered the active whisking field. Trial-to-trial variation in the size of this response was explained by the position of the whisker upon touch. Taken together, these data indicate that SC neurons linearly combine an internal estimate of self-motion with external stimulation to enable active tactile localization.

neuroscience↗

bioRxiv2022

Two complimentary codes in the superior colliculus differentiate external from self-generated tactile cues

During tactile localization, animals must differentiate stimuli caused by their own volitional movement from externally generated object motion. To determine a neural basis for this ability, we examined the mouse superior colliculus (SC), which contains multiple egocentric maps of sensorimotor space. By placing mice in a whisker-guided virtual reality, we discovered a rapidly adapting neural response that strongly preferred external over self-generated changes in tactile space. This transient response only emerged when external motion gained contact with a whisker, arguing that stimulus adaptation was whisker-specific. The accumulation of sensory evidence through active sensing and repetitions in external motion controlled the size of the transient response. Population-level firing rates among transiently responsive neurons accurately encoded the direction of external motion. These data reveal that stimulus-specific adaptation together with accumulating sensorimotor predictions in SC neurons enhance the localization of unexpected motion in the environment.

neuroscience↗