Biology subjects

Golowasch, J.

Publications and source records attributed to Golowasch, J..

4 recordsLinked to original sources

bioRxiv2026

Long-Term Neuromodulatory Effects on the Ionic Current Parameter Space of Oscillatory Neurons

Neurons are constantly subject to short-term neuromodulatory effects through the regulation of various proteins, including ion channels. However, the long-term influences of neuromodulators remain poorly understood. Multiple ionic currents work in concert to generate oscillatory neuronal activity, and long-term neuromodulatory effects on them likely differ from short-term effects. Here we examined the long-term effects of the neuromodulatory environment on the ionic conductances that generate the rhythmic activity of a well-known neuronal network, the crustacean pyloric network. We measured most of the known voltage-dependent and synaptic currents expressed by two identified neurons in their normal neuromodulatory environment and after prolonged removal of neuromodulators. To understand the global conductance makeup of these cells, we defined the conductance parameter space of each cell as the multidimensional volume occupied by its conductances in a population of identical neurons. We then examined the changes in this volume after independently modifying the neuromodulator environment and activity of these neurons. Both neuromodulation and activity appear to constrain the conductance parameter space in pyloric neurons, suggesting a general phenomenon. Interestingly, while neuromodulators appear to exert a similar regulatory effect on both cells, activity seems to do so in a cell-type-specific manner. Our results suggest a mechanism that explains why the same manipulation of the neuromodulatory input does not produce the same change in network activity across animals: the degeneracy of the pacemaker mechanism. SignificanceHow does a rhythm-generating neuronal network recover its rhythm after its disruption? Neuromodulators control neuronal activity, especially rhythmic activity, which is vital to animals. Thus, neuronal network robustness and the ability to recover from major perturbations are of crucial importance. We tested the hypothesis that neuromodulators constrain the entire neuronal ionic conductance parameter space in a well-characterized network. Our results confirm that neuromodulators and activity regulate the global neuronal conductance landscape. Our results suggest a mechanism that explains why the same manipulation of the neuromodulatory environment produces distinct effects on network activity across individuals: the degeneracy of the pacemaker mechanism. These results support the need to consider individualized approaches to understand functional mechanisms and to develop therapies for pathological conditions.

neuroscience↗

bioRxiv2022

Daily and cell type-specific membrane capacitance changes in mouse cortical neurons

Capacitance of biological membranes is determined by the properties of the lipid portion of the membrane, as well as morphological features of a cell. In neurons, membrane capacitance is a determining factor of synaptic integration, action potential propagation speed and firing frequency due to its direct effect on the membrane time constant. Besides slow changes associated with increased morphological complexity during postnatal maturation, neuron membrane capacity is largely considered a stable, non-regulated constant magnitude. Here we report that in two excitatory neuronal cell types, pyramidal cells of mouse primary visual cortex and granule cells of the hippocampus, the membrane capacitance significantly changes between the start and the end of a daily light cycle. The changes are large, nearly two-fold in magnitude in pyramidal cells, but are not observed in cortical parvalbumin-expressing inhibitory interneurons. We discuss potential functional implications and plausible mechanisms.

neuroscience↗

bioRxiv2017

A Balance Of Outward And Linear Inward Ionic Currents Is Required For The Generation Of Slow Wave Oscillations

Regenerative inward currents help produce slow oscillations through a negative-slope conductance region of their current-voltage relationship that is well approximated by a linear negative conductance. We used dynamic clamp injections of a linear current with this conductance, INL, to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question, in synaptically isolated neurons of the crab Cancer borealis, after blocking action potentials. The pyloric network consists of distinct pacemaker group and follower neurons, all of which express the same complement of ionic currents. When the pyloric dilator (PD) neuron, a member of the pacemaker group, was injected with INL using dynamic clamp, it consistently produced slow oscillations. In contrast, the lateral pyloric (LP) or ventral pyloric (VD) follower neurons, failed to oscillate with INL. To understand these distinct behaviors, we compared outward current levels of PD, LP and VD neurons. We found that LP and VD neurons had significantly larger high-threshold potassium currents (IHTK) than PD, and LP had lower transient potassium current, IA. Reducing IHTK pharmacologically enabled both LP and VD neurons to produce oscillations with INL, whereas modifying IA levels did not affect INL-induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of IHTK can block INL-induced oscillatory activity, whereas generation of oscillations is almost independent of IA levels. These results demonstrate the importance of a balance between inward pacemaking currents and high-threshold K+current levels in determining slow oscillatory activity.

neuroscience↗

bioRxiv2017

Single-Neuron Gene Expression Analysis Using the Maxwell 16 LEV System in the Neural Systems and Behavior Course

Gene expression analysis from single cells has become increasingly prominent across biological disciplines; thus, it is important to train students in these approaches. Here, we present an experimental and analysis pipeline that we developed for the Neural Systems & Behavior (NS&B) course at Marine Biological Laboratory. Our approach used the Maxwell(R) 16 LEV simplyRNA Tissue Kit and GoTaq(R) 2-Step RT-qPCR System for gene expression analysis from single neurons of the crustacean stomatogastric ganglion, a model system to study the generation of rhythmic motor patterns. We used double-stranded RNA to knockdown expression of a putative neuromodulator-activated sodium channel. We then examined the electrophysiological responses to known neuromodulators and confirmed that the response was reduced. Finally, we measured how mRNA levels of several ion channel genes changed in response. Our results provide new insights into the neural mechanisms underlying the generation and modulation of rhythmic motor patterns.

neuroscience↗