Modulación sináptica del umbral de reclutamiento y de la frecuencia de potenciales de acción en las motoneuronas oculares

Resumo

Neurons receive and integrate synaptic signals, which can generate action potentials as a mechanism to transmit information. The neuronal input-output function can be set by changes in the recruitment threshold and in the gain. Studies in alert preparations have demonstrated that extraocular muscle motoneurons exhibit a phasictonic firing rate related to eye velocity and position, respectively. The slopes of these relationships are higher in motoneurons with higher recruitment thresholds and it has been proposed that this relationship depends upon synaptic inputs. On the other hand, these motoneurons receive abundant synaptic inputs mediated by glutamate and γ- amino butyric acid (GABA) neurotransmitters from different premotor sources. The present work investigates the modulation of the recruitment threshold and gain by glutamate and GABA in the rat oculomotor nucleus motoneurons, and questions if such processes could depend on motoneuron size. In a first experimental group, motoneurons were recorded in a brain slice preparation in control conditions and during glutamate (5 µM) application to the bath. Glutamate did not affect membrane potential or input resistance, but produced a decrease in rheobase and depolarization voltage that was dependent on recruitment threshold current. These changes were produced by a diminution in voltage threshold to evoke an action potential. In addition, glutamate compressed the range of recruitment threshold current compared to control. Motoneurons exposed to glutamate also showed an increase in the tonic frequency gain and in the peak firing frequency; such increments depended on the recruitment threshold current. In conclusion, glutamate modulates tonic and phasic discharge properties by changes in active membrane properties (action potential threshold and gain). These changes co-varied with the recruitment threshold current and motoneuron size. A second experimental group was aimed at determining how high and low ambient GABA concentrations modulate the input-output relationship of extraocular muscle motoneurons. These two experimental conditions were carried out because phasic inhibition mediated by γ-amino butyric acid (GABA) occurs when a high concentration of GABA at the synaptic cleft activates postsynaptic GABAA receptors. This process allows neuronal information transfer. In addition, in some neuronal populations, low concentrations of GABA activate non-synaptic GABAA receptors and generate a tonic inhibition, which could modulate cell excitability. Superfusion of brain slices with GABA (100 µM) produced a sustained GABAA receptor-mediated current (~129 pA) that reduced the input resistance, increased the recruitment threshold and shifted the firing frequency-current relationship rightward without any change in gain. These GABA mediated modifications did not depend on motoneuron size and were mainly due to the activation of low-affinity GABAA receptors, i.e. those involved in the fast postsynaptic events. In absence of exogenous GABA, the application of 20 µM gabazine (an antagonist of GABAA receptors) abolished spontaneous inhibitory postsynaptic currents and revealed a tonic current (~9 pA) in motoneurons. Gabazine exposure increased the input resistance as a function of motoneuron size. As a consequence of shunting, the reduction in recruitment threshold was more pronounced in larger motoneurons. Also, the firing frequency-current relationship shifted to the left, without any change in gain. Gabazine effects were chiefly due to motoneuron tonic inhibition because tonic current amplitude was five-fold greater than phasic. Tonic current were due to high-affinity GABAA receptors, which are located extrasynaptically. This study demonstrates a tonic inhibition in extraocular muscle motoneurons that modulates recruitment threshold depending on cell size. We concluded that glutamate modulates active membrane properties (voltage threshold and gain), while tonic GABAA receptor-mediated current modulates passive membrane properties (input resistance). The effects of these neurotransmitters upon recruitment threshold and gain increased with motoneuron size. These effects mediated by metabotropic glutamate receptors and GABAA receptor mediated tonic current would allow motoneurons to be recruited and for there to be an increased firing rate gain with reduced excitatory inputs. We propose that glutamate and GABA act in an orchestrated manner to refine the motor output, allowing fixations of eye in eccentric positions in the orbit and accurate saccadic eye movement with high velocity.