Biology subjects

Prinz, A. A.

Publications and source records attributed to Prinz, A. A..

4 recordsLinked to original sources

bioRxiv2025

Plasticity in thoracic paravertebral sympathetic postganglionic neurons after high spinal cord transection

Various pre-sympathetic descending brain circuits recruit spinal cord preganglionic neurons to encode central sympathetic drive via their synaptic actions onto sympathetic postganglionic neurons (SPNs) - the final sympathetic output neurons. Thoracic paravertebral ganglia SPNs (tSPNs) provide distributed control over body tissue systems via functional subpopulations. High thoracic spinal cord injuries (SCIs) compromise descending excitatory drive to SPNs, causing dysautonomias including hypotension. In adult mice, we tested whether the SCI-induced chronic reduction in tSPN activity leads to homeostatic increases in their excitability. tSPN excitability spanned a >10 fold range in both sham and SCI populations, governed by a strong linear (ohmic) relationship between cell resistance and threshold depolarizing current (rheobase), with a clear trend towards increased excitability after SCI. Dendritic length was reduced, as was measured cell capacitance in Neuropeptide Y expressing (NPY+) tSPNs (putative vasoconstrictors), which represent >40% of tSPNs. NPY+ tSPNs also had changes in active membrane properties including an increased repetitive firing output gain ({uparrow}f-I slope), which modelling attributed to reduced delayed rectifier currents (IK). After SCI, spontaneous quantal excitatory synaptic frequency increased overall (226%) and in the NPY+ tSPN subpopulation (300%); their temporal summation recruited spiking in 10.5% of sham and 22.2% of SCI recordings. Computational modeling showed that spontaneous synaptic activity was particularly effective at recruiting spiking after SCI. Overall, tSPNs, including in vasoconstrictors, appear to undergo CNS-independent compensatory increases in excitability after SCI. The alterations further contribute to observed central and peripheral changes that limit hypoactivity and hypotension but exaggerate reflex responses. Significance StatementRecruited by preganglionic neurons located in thoracolumbar spinal cord, sympathetic postganglionic neurons (SPNs) represent the final step in sympathetic neural homeostatic control of target organs. The dramatic reductions or complete loss of brain pre-sympathetic drive in higher level spinal cord injuries (SCIs) contribute to emergent dysautonomias. Given the crucial role of SPNs in maintaining organismal homeostasis, we undertook comprehensive studies to test whether thoracic SPNs undergo homeostatic compensatory increases in their cellular excitability weeks after a high thoracic SCI. We observed changes consistent with increased cellular and synaptic excitability including in SPN vasoconstrictors, whose increased output gain, could mitigate hypotension but also strengthen hypertensive responses generated by afferent-driven exaggerated preganglionic drive (e.g. autonomic dysreflexia).

neuroscience↗

bioRxiv2024

Generation of motor program diversity and variability through inhibitory circuit motifs in the Drosophila larval locomotor system

How do neural networks generate and regulate diversity and variability in motor outputs with finite cellular components? Here we examine this problem by exploring the role that inhibitory neuron motifs play in generating mixtures of motor programs in the segmentally organised Drosophila larval locomotor system. We developed a computational model that is constrained by experimental calcium imaging data. The model comprises single-compartment cells with a single voltage-gated calcium current, which are interconnected by graded excitatory and inhibitory synapses. Local excitatory and inhibitory neurons form conditional oscillators in each hemisegment. Surrounding architecture reflects key aspects of inter- and intrasegmental connectivity motifs identified in the literature. The model generates metachronal waves of activity that recapitulate key features of fictive forwards and backwards locomotion, as well as bilaterally asymmetric activity in anterior regions that represents fictive head sweeps. The statistics of inputs to competing command-like motifs, coupled with inhibitory motifs that detect activity across multiple segments generate network states that promote diversity in motor outputs, while at the same time preventing maladaptive overlap in motor programs. Overall, the model generates testable predictions for connectomics and physiological studies while providing a platform for uncovering how inhibitory circuit motifs underpin generation of diversity and variability in motor systems.

neuroscience↗

bioRxiv2023

Temporal dynamics of Na/K pump mediated memory traces: insights from conductance-based models of Drosophila neurons

Sodium potassium ATPases (Na/K pumps) mediate long-lasting, dynamic cellular memories that can last tens of seconds. The mechanisms controlling the dynamics of this type of cellular memory are not well understood and can be counterintuitive. Here, we use computational modeling to examine how Na/K pumps and the ion concentration dynamics they influence shape cellular excitability. In a Drosophila larval motor neuron model, we incorporate a Na/K pump, a dynamic intracellular Na+ concentration, and a dynamic Na+ reversal potential. We probe neuronal excitability with a variety of stimuli, including step currents, ramp currents, and zap currents, then monitor the sub- and suprathreshold voltage responses on a range of time scales. We find that the interactions of a Na+-dependent pump current with a dynamic Na+ concentration and reversal potential endow the neuron with rich response properties that are absent when the role of the pump is reduced to the maintenance of constant ion concentration gradients. In particular, these dynamic pump-Na+ interactions contribute to spike rate adaptation and result in long-lasting excitability changes after spiking and even after sub-threshold voltage fluctuations on multiple time scales. We further show that modulation of pump properties can profoundly alter a neurons spontaneous activity and response to stimuli by providing a mechanism for bursting oscillations. Our work has implications for experimental studies and computational modeling of the role of Na/K pumps in neuronal activity, information processing in neural circuits and the neural control of animal behavior.

neuroscience↗

bioRxiv2020

Neural network models of object recognition can also account for visual search behavior.

To find an object we are looking for, we must recognize it. Prevailing models of visual search neglect recognition, focusing instead on selective attention mechanisms. These models account for performance limitations that participants exhibit when searching highly simplified stimuli often used in laboratory tasks. However, it is unclear how to apply these models to complex natural images of real-world objects. Deep neural networks (DNN) can be applied to any image, and recently have emerged as state-of-the-art models of object recognition in the primate ventral visual pathway. Using these DNN models, we ask whether object recognition explains limitations on performance across visual search tasks. First, we show that DNNs exhibit a hallmark effect seen when participants search simplified stimuli. Further experiments show this effect results from optimizing for object recognition: DNNs trained from randomly-initialized weights do not exhibit the same performance limitations. Next, we test DNN models of object recognition with natural images, using a dataset where each image has a visual search difficulty score, derived from human reaction times. We find DNN accuracy is inversely correlated with visual search difficulty score. Our findings suggest that to a large extent visual search performance is explained by object recognition.

animal behavior and cognition↗