Development of Intrinsic Motoneuron Properties in Humans
Creators: Mohammadalinejad, Ghazaleh
Publisher: name: University of Alberta Library
Year: 2023

<p>Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators like serotonin. In this thesis we examined intrinsic motoneuron properties in 50 typically developing participants ranging in age from 7 to 53 years. The primary objective was to investigate the age-related development of persistent inward currents (PICs) and spike frequency adaptation in a young development group (aged 7 to 17 years), a young adult group (aged 18 to 28 years) and an older adult group (aged 32 to 53 years). PICs are predominantly mediated by voltage- and calcium-dependent calcium and sodium ions, and they provide a long-lasting intrinsic depolarization to the motoneuron to help amplify and prolong synaptic inputs. To assess the contribution of the PIC to the self-sustained firing of motoneurons, we measured multiple single motor units from the tibialis anterior (TA) muscle, an ankle dorsiflexor, using a 64-electrode surface electromyography (EMG) grid. The firing frequency (F) profiles of low threshold motor units were used to estimate the synaptic input to the TA motoneuron pool given their linear response to synaptic inputs. The contribution of the PIC to self-sustained firing was estimated based on the estimated synaptic input required to de-recruit the motor unit compared to the input needed for recruitment (ΔF) during a slowly increasing and then decreasing isometric dorsiflexion. ΔF was larger in the young development group (~ 5.8 Hz, n = 20) compared to the young (~ 4.9 Hz, n = 13) and older (~ 4.8 Hz, n = 8) adult groups, consistent with a developmental decrease in PIC-mediated self-sustained firing. ΔF was also larger in a subset of participants taking selective serotonin reuptake inhibitors (SSRIs: ~ 6.5 Hz, 11 to 28 years old, n = 9) compared to their age-matched controls (~ 5.3 Hz, n = 26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. <br>
We also investigated how potential intrinsic conductances may affect the nonlinear firing behavior of the motor units (motoneurons) in response to a presumed linear increase in synaptic drive by quantifying the slope and duration of three iteratively joined lines fit to the ascending firing rate profile. We proposed that the firing rate acceleration at the onset of motor unit discharge reflects the acceleration in membrane depolarization during the onset of PIC activation (termed secondary range) and the shallower increase in firing that follows this reflects motoneuron discharge during full PIC activation (termed tertiary range). In some motor units, firing rates also decreased before peak torque was reached (termed tertiary sag range) and we proposed this reflects spike frequency adaptation, another intrinsic property of the motoneuron. Participants in the young development and SSRI groups had steeper secondary range slopes (~ 5.7 and 7.2 Hz/s, respectively) compared to the young and older adult groups (both ~ 4.3 Hz/s), consistent with the PIC in the former two groups producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In contrast, there were no changes in the slope or duration of the tertiary range between the different age groups or in response to SSRI intake. The slope of the tertiary sag range also decreased with age across the young development and young adult groups (r = -0.38, n = 33) and was steeper in the SSRI group (-2.9 Hz/s) compared to the age-matched controls (-1.7 Hz/s), an unexpected finding considering that large PICs are associated with reduced spike frequency adaptation. Moreover, both the young development and SSRI groups exhibited higher start, maximum and/or end firing rates, potentially due to higher synaptic drives in the young development group and from increases in motoneuron excitability in the SSRI group. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the young and older adults which may have been balanced by an increase in spike frequency adaptation. The increased motoneuron excitability in the young development group was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge that vary during development with a similar time course to the changes in motoneuron firing behaviour observed in this thesis.  </p>