Sympathetic motor neuron dysfunction is a missing link in age-associated sympathetic overactivity

de la Cruz, Lizbeth1; Bui, Derek1; Moreno, Claudia1 ; Vivas, Oscar 1

Published Feb 25, 2025 on Dryad. https://doi.org/10.5061/dryad.z08kprrpp

Data files

Feb 25, 2025 version files 141.18 KB

Abstract

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.

https://doi.org/10.5061/dryad.z08kprrpp

Description of the data and file structure

Data from recordings of sympathetic neurons comparing three ages in mice. Data include current-clamp and voltage-clamp recordings. Quantification and analyses presented in the manuscript were performed in Prism. Files uploaded here were copied to Excel. Files are separated for each figure.

Files and variables

File: Figure_8_de_la_Cruz.xlsx

Description: Data from Figure 8 containing measurements of the resting membrane potential in the presence of retigabine (Sheet 1) and linopirdine (Sheet 2). They contain three columns named Before, After, and Recovery, and the units are mV. Rows are paired measurements for each cell.

File: Figure_4_de_la_Cruz.xlsx

Description: Data from Figure 4 containing measurements of electrophysiological recordings comparing young, middle-aged, and old mice. Each sheet contains a measured parameter. Sheet 1 contains data used to create stimulus-response curves. Column A is the stimulus applied with units of pico amperes. All the other columns are the responses from each cell, and they are divided into three age groups. The numbers are the # of action potentials quantified for each stimulus in each cell. Sheet 2 contains the number of action potentials at the maximum stimulus (100 pA). The data comes from Sheet 1. Sheet 3 contains the number of spontaneous action potentials. Zeros were not included when plotting the number of spontaneous firing action potentials and therefore are labeled in blue. Sheet 4 contains the values of rheobase with units of mV. Sheet 5 contains the values of capacitance, measured after going the whole cell and compensating capacitive transients. Sheet 6 contains the values of resting membrane potential with values of mV. Sheet 7 contains the values of input resistance with units of Mega Ohms. Sheets 8 to 10 contain the percentage of neurons firing and non-firing for young (sheet 7), middle-aged (sheet 8), and old (sheet 9) mice.

File: Figure_5_de_la_Cruz.xlsx

Description: Data from Figure 5 contains current-clamp recordings separated by neuron firing type and age group. Sheet 1 contains the values of resting membrane potential with units in mV. Columns A to C are data in the category of neurons firing in single action potentials but for different ages. Columns D to F are data in the category of neurons with phasic firing but for different ages. Columns G to I are data in the category of neurons with tonic firing but for different ages. Sheet 2 contains the values of resting membrane potential with units in mV separated only by neuron firing type but compiling data from all ages. Sheet 3 contains the input resistance values with units of mega Ohms. Columns A to C are data in the category of neurons firing in single action potentials but for different ages. Columns D to F are data in the category of neurons with phasic firing but for different ages. Columns G to I are data in the category of neurons with tonic firing but for different ages. Sheet 4 contains the input resistance values with units of mega Ohms separated only by neuron firing type but compiling data from all ages. Sheet 5 contains the number of spontaneous action potentials. Columns A to C are data in the category of neurons firing in single action potentials but for different ages. Columns D to F are data in the category of neurons with phasic firing but for different ages. Columns G to I are data in the category of neurons with tonic firing but for different ages. Sheet 6 contains the number of spontaneous action potentials separated only by neuron firing type but compiling data from all ages. Sheet 7 contains the values of the number of action potentials fired at the maximum stimulus (100 pA). Columns A to C are data in the category of neurons firing in single action potentials but for different ages. Columns D to F are data in the category of neurons with phasic firing but for different ages. Columns G to I are data in the category of neurons with tonic firing but for different ages. Sheet 8 contains the values of the number of action potentials fired at the maximum stimulus (100 pA) separated only by neuron firing type but compiling data from all ages. Sheet 9 contains the values of M current density with units of pA/pF. Columns A to C are data in the category of neurons firing in single action potentials but for different ages. Columns D to F are data in the category of neurons with phasic firing but for different ages. Columns G to I are data in the category of neurons with tonic firing but for different ages. Sheet 10 contains the values of M current density with units of pA/pF separated only by neuron firing type but compiling data from all ages. Sheets 11 to 13 contain the number of neurons in each of the three firing patterns for young (sheet 11), middle-aged (sheet 12), and old (sheet 13) mice.

File: Figure_6_de_la_Cruz.xlsx

Description: Data from Figure 6 containing data used to understand the relationship between M-current amplitude and the resting membrane potential or the maximum number of action potentials. Sheets 1 to 5 compare M current with the resting membrane potential. Column A in sheets 1 to 3 contains values of current density with units of pA/pF. Column B in sheets 1 to 3 contains values of the resting membrane potential with units of mV. Sheet 4 contains values of the correlation coefficient r, and sheet 5 is the slope. Sheets 6 to 8 compare M current with the maximum number of action potentials from neurons isolated from young (sheet 6), middle-aged (sheet 7), and old (sheet 8) mice. Column A contains values of current density with units of pA/pF. Column B contains values of the number of action potentials.

File: Figure_7INa_de_la_Cruz.xlsx

Description: Data from Figure 7 containing voltage-clamp recordings of sodium currents. Sheet 1 contains data used to create curves with the current-voltage relationship. Column A is the voltage applied with units of mV. All the other columns are the sodium current density from each cell and are divided into three age groups. The numbers have units of pA/pF. Sheet 2 contains the absolute maximum sodium current density comparing age groups.

File: Figure_7IK_de_la_Cruz.xlsx

Description: Data from Figure 7 containing voltage-clamp recordings of potassium currents. Sheet 1 contains data used to create curves with the current-voltage relationship. Column A is the voltage applied with units of mV. All the other columns are the potassium current densities from each cell. The numbers have units of pA/pF. Columns B to J contains data from cells treated with the drug XE-991 in young neurons. Columns L to S contain data from cells treated with the drug XE-991 in old neurons. Columns V to Y contains data from cells treated with the combination of drugs PTX and Gtx in young neurons. Columns AF to AN contain data from cells treated with the combination of drugs PTX and Gtx in old neurons.