Biology subjects

Leao, R. M.

Publications and source records attributed to Leao, R. M..

4 recordsLinked to original sources

bioRxiv2021

Development of spontaneous firing of fusiform neurons from the dorsal cochlear nucleus of mice occurs after hearing onset.

The dorsal cochlear nucleus (DCN) in the auditory brainstem integrates auditory and somatosensory information. Mature fusiform neurons express two qualitative intrinsic states in equal proportions: quiet, with no spontaneous regular action potential firing, or active, with regular spontaneous action potential firing. However, how these firing states and other electrophysiological properties of fusiform neurons develop during early postnatal days to adulthood is not known. Thus, we recorded fusiform neurons from mice from P4 to P21 and analyzed their electrophysiological properties. In the pre-hearing phase (P4-P13), we found that fusiform neurons are mostly quiet, with the active state emerging after hearing onset at P14. Subthreshold properties present more variations before hearing onset, while action potential properties vary more after P14, developing bigger, shorter, and faster action potentials. Interestingly, the activity threshold is more depolarized in pre-hearing cells suggesting that persistent sodium current (INaP) increases its expression after hearing. In fact, INaP increases its expression after hearing, accordingly with the development of active neurons. Thus, we suggest that the post-hearing expression of INaP creates the active state of the fusiform neuron. At the same time, other changes refine the passive membrane properties and increase the speed of action potential firing of fusiform neurons.

neuroscience↗

bioRxiv2020

ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem.

Cartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, the principal excitatory neuron in the DCN. Most cartwheel neurons present spontaneous firing (active neurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a smaller fraction does not fire spontaneously (quiet neurons). Additionally, hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Due to its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons. We found that quiet neurons express an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP) antagonist. After its inhibition, quiet neurons start to fire spontaneously, while the behavior of active neurons was not affected. On the other hand, in active neurons, KATP agonist diazoxide activated a conductance similar to the KATP conductance of quiet neurons and stopped spontaneous firing. According to the effect of KATP channels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Finally, slices incubated with the tinnitus-inducing agent sodium salicylate presented more quiet neurons expressing the KATP conductance, which increased the proportion of quiet neurons. Our results reveal an unexpected role of KATP channels in controlling the spontaneous firing of neurons. Additionally, changes in KATP channel activity of cartwheel neurons can be related to the DCN hyperactivity seen in tinnitus.

neuroscience↗

bioRxiv2019

Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor

Exposure to humans and experimental animals to loud noises produce cognitive and emotional disorders and recent studies have shown that hippocampal neuronal function is affected by auditory stimulation or deprivation. We have found previously that in the hippocampus of rats exposed to high-intensity sound (110 dB) for one-minute the Schaffer-CA1 long-term potentiation (LTP) is strongly inhibited. Here we investigated possible mechanisms involved in this effect. We found, using c-fos expression, that exposure to 110 dB sound-activated neurons in the CA1 and CA3 hippocampal region. Using electrophysiological recordings in hippocampal slices, we found that both GABAergic and glutamatergic neurotransmission were unaffected by high-intensity sound stimulation. However, hippocampal brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity, presented decreased levels in sound-stimulated animals. Perfusion of slices with BDNF revert the inhibition of LTP after a single sound stimulus in comparison to sham-stimulated rats. Furthermore, the perfusion with LM 22A4, a TrkB receptor agonist also rescued LTP from sound-stimulated animals. Our results strongly suggest that the exposure to high-intensity sound inhibits the BDNF production in the hippocampus, which could be a possible mechanism of the inhibition of LTP by high-intensity sound exposure.

neuroscience↗

bioRxiv2018

Increased hippocampal GABAergic inhibition after long-term high-intensity sound exposure

Exposure to loud sounds has been related to deleterious mental and systemic effects in addition to auditory maladies. Hippocampal function has been shown to be affected to either high intensity sound exposure or long-term sound deprivation. Hippocampal long-term potentiation (LTP) is inhibited after 10 days of daily exposure to 2 minutes of high-intensity noise (110 dB), in the hippocampi of Wistar rats. He we investigate how the glutamatergic and GABAergic neurotransmission mediated by ionotropic receptors is affected by the same protocol of high intensity sound exposure. We found that while the glutamatergic transmission both by AMPA/kainite and NMDA receptors in the Schaffer-CA1 synapses is largely unaffected by long-term exposure to high intensity sound, the amplitude of the inhibitory GABAergic currents is potentiated, but not the frequency of the both spontaneous and miniature currents. We conclude that GABAergic transmission is potentiated at the post-synaptic level in the hippocampal CA1 pyramidal neurons after a prolonged exposure to short periods of high-intensity sound. This effect could be an important factor for the reduced LTP in the hippocampi of these animals after high intensity sound exposure, and demonstrated that prolonged exposure to high- intensity sound can affect hippocampal inhibitory transmission and consequently its function.

neuroscience↗