Ricardo Mauricio Leao

University of São Paulo | USP · Departamento de Fisiologia (Ribeirão Preto)

Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons. However, the mechanism invol...

Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons from juvenile rats. However,...

Sepsis is associated with numerous physiological and biochemical abnormalities that result in a life-threatening condition. The involvement of the Central Nervous System (CNS) during sepsis has received considerable attention, especially the hippocampus which plays a key role in the learning and memory processes. The increased interest in this limb...

The dorsal cochlear nucleus (DCN) in the auditory brainstem integrates auditory and somatosensory information. Mature DCN fusiform neurons fall into two qualitatively distinct types: quiet, with no spontaneous regular action potential firing, or active, with regular spontaneous action potential firing. However, how these firing states and other ele...

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway initiated by the enzyme i...

High doses of salicylate induce tinnitus in humans and experimental animals. The Dorsal Cochlear Nucleus is implicated with the genesis of tinnitus, and increased activity in this nucleus is seen in animal models of tinnitus. Incubation of brainstem slices containing the DCN with millimolar salicylate reduces the spontaneous firing of glycinergic c...

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 state...

Exposure to noise produces cognitive and emotional disorders, and recent studies have shown that auditory stimulation or deprivation affects hippocampal function. Previously, we showed that exposure to high-intensity sound (110 dB, 1 min) strongly inhibits Schaffer-CA1 long-term potentiation (LTP). Here we investigated possible mechanisms involved...

Neuropathic pain is triggered by injury to the somatosensory system, and is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. Here, we show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzy...

Key points Cartwheel neurons provide potent inhibition to fusiform neurons in the dorsal cochlear nucleus (DCN). Most cartwheel neurons fire action potentials spontaneously, but the ion channels responsible for this intrinsic activity are unknown. We investigated the ion channels responsible for the intrinsic firing of cartwheel neurons and the sta...

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 do...

During prolonged dehydration, body fluid homeostasis is challenged by extracellular fluid (ECF) hyperosmolality, which induce important functional changes in the hypothalamus, in parallel with other effector responses, such as the activation of the local renin-angiotensin system (RAS). Therefore, in the present study we investigated the role of sod...

Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexpone...

Here, we investigated the participation of pro and anti-inflammatory cytokines in the spread of repeated audiogenic seizures from brainstem auditory structures to limbic areas, including the hippocampus. We used Wistar Audiogenic Rats (WARs) and Wistars submitted to the audiogenic kindling protocol with a loud broad-band noise. We measured pro and...

We are pleased to present ou new research article. https://doi.org/10.1016/j.brainres.2019.146570

While acute audiogenic seizures in response to acoustic stimulus appear as an alteration in sensory-motor processing in the brainstem, the repetition of the stimulus leads to the spread of epileptic activity to limbic structures. Here, we investigated whether animals of the Wistar Audiogenic Rat (WAR) strain, genetically selected by inbreeding for...

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 lo...

Physical exercise-induced inflammation may be beneficial when exercise is regular but it may be harmful when exercise is intense and performed by unaccustomed individuals/rats. Molecular hydrogen (H2) has recently emerged as a powerful anti-inflammatory, antioxidant and anti-apoptotic molecule in a number of pathological conditions, but little is k...

Exposure to loud sounds is related to harmful mental and systemic effects. The hippocampal function can be affected to either high-intensity sound exposure or long-term sound deprivation. We previously showed that hippocampal long-term potentiation (LTP) is inhibited after ten days of daily exposure to 2 minutes of high-intensity noise (110 dB), in...

Key points Neurons from the brainstem nucleus of the tractus solitarius (NTS) participate in the counter‐regulatory mechanisms in response to hypoglycaemia. ATP‐sensitive potassium (KATP) channels are expressed in NTS neurons, and are partially open at rest in normoglycaemic 5 mM glucose. In normoglycaemic conditions, most NTS neurons depolarize in...

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-in...

The auditory part of the brainstem is composed of several nuclei specialized in the computation of the different spectral and temporal features of the sound before it reaches the higher auditory regions. There are a high diversity of neuronal types in these nuclei, many with remarkable electrophysiological and synaptic properties unique to these st...

Despite the many studies focusing on epilepsy, a lot of the basic mechanisms underlying seizure susceptibility are mainly unclear. Here, we studied cellular electrical excitability, as well as excitatory and inhibitory synaptic neurotransmission of CA1 pyramidal neurons from the dorsal hippocampus of a genetic model of epilepsy, the Wistar Audiogen...

The brain demands constant supply of glucose-derived energy for cell metabolism and survival, and brain hypoglycemia may compromise synaptic functions. The brainstem nucleus of the tractus solitarius (NTS) is an integrative center for autonomic counterregulatory responses to hypoglycemia, and recent evidences have demonstrated that NTS neurons can...

Afferent neurotransmission to hippocampal pyramidal cells can lead to long‐term changes to their intrinsic membrane properties and affect many ion currents. One of the most plastic neuronal currents is the hyperpolarization activated cationic current (Ih), which changes in CA1 pyramidal cells in response to many types of physiological and pathologi...

The brainstem nucleus of the tractus solitarius (NTS) is an integrative center for the counterregulatory responses to hypoglycemia, and recent evidences have showed that NTS neurons can directly sense extracellular glucose fluctuations via mechanisms that rely on glucose metabolism. The ATP‐sensitive potassium (K ATP ) channels play a key role in l...

Afferent neurotransmission on hippocampal pyramidal cells can change their intrinsic membrane properties and affect many ion currents. One of the most plastic neuronal currents is the hyperpolarization activated cationic current (Ih), which changes in CA1 pyramidal cells in responseto many types of physiological and pathological processes. Several...

The negative slope conductance created by the persistent sodium current (INaP) prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a recent study, we demonstrated that this effect was due to an increase of the membrane time constant. When the negative slope conductance opposes completely the positive slope conductances of the...

The Dorsal Cochlear Nucleus (DCN) is a region which has been traditionally linked to the genesis of tinnitus, the constant perception of a phantom sound. Sodium salicylate, a COX-2 inhibitor, can induce tinnitus in high doses. Hyperactivity of DCN neurons is observed in several animal models of tinnitus, including salicylate-induced tinnitus. The D...

Exposure to loud sounds has become increasingly common. The most common consequences of loud sound exposure are deafness and tinnitus, but emotional and cognitive problems are also associated with loud sound exposure. Loud sounds can activate the hipothalamic-pituitary-adrenal axis resulting in the secretion of corticosterone, which affects hippoca...

Based on passive cable theory, an increase in membrane conductance produces a decrease in the membrane time constant and input resistance. Unlike the classical leak currents, voltage-dependent currents have a nonlinear behavior which can create regions of negative conductance, despite the increase in membrane conductance (permeability). This negati...

Neuronal subthreshold voltage-dependent currents determine membrane properties such as the input resistance (Rin) and the membrane time constant (τm) in the subthreshold range. In contrast with classical cable theory predictions, the persistent sodium current (INaP), a non-inactivating mode of the voltage-dependent sodium current, paradoxically inc...

[This corrects the article on p. 249 in vol. 10, PMID: 27833532.].

Neurons from the dorsal cochlear nucleus (DCN) present endocannabinoid (EC) dependent short-term synaptic plasticity in the form of depolarization-induced suppression of excitation (DSE). Post-synaptic calcium influx promotes EC synthesis and depression of neurotransmission. ECs can be degraded by a hydrolytic and an oxidative pathway, the latter v...

A change of the input resistance (Rin) of the neuron involves a change in the membrane conductances by opening and closing of ion channels. In passive membranes, i.e., membranes with only linear leak conductances, the increase or decrease of these conductances leads to a decrease or increase of the Rin and the membrane time constant (τm). However,...

In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known....

Introduction: Salicylate at high doses induces tinnitus in humans and experimental animals. However, the mechanisms and loci of action of salicylate in inducing tinnitus are still not well known. The expression of Immediate Early Genes (IEG) is traditionally associated with long-term neuronal modifications but it is still not clear how and where I...

Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal prop...

High intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can produce synaptic plasticity events...

New Findings What is the central question of this study? What is the effect of chronic intermittent hypoxia (a neurogenic model of hypertension that also induces active expiration) on intrinsic electrophysiological properties of rostral ventrolateral medulla presympathetic and putative expiratory neurons recorded in brainstem slices of juvenile rat...

Caramboxin: Patients suffering from chronic kidney disease are frequently intoxicated after ingesting star fruit. The main symptoms of this intoxication are named in the picture. Bioguided chemical procedures resulted in the discovery of caramboxin, which is a phenylalanine-like molecule that is responsible for intoxication. Functional experiments...

Das wirksame und tödliche Neurotoxin Caramboxin wurde aus Sternfrüchten extrahiert, wie N. Garcia‐Cairasco, N. P. Lopes et al. in der Zuschrift auf S. 13305 ff. beschreiben. Hauptsächlich betroffen durch Caramboxin‐Vergiftung sind die Nieren und das Gehirn. Ein stärkeres Bewusstsein für die Gefahren dieses neuen Phenylalanin‐ähnlichen Neurotoxins i...

The potent and deadly neurotoxin caramboxin was extracted from star fruits, as N. Garcia‐Cairasco, N. P. Lopes, et al. describe in their Communication on page 13067 ff. The main targets of caramboxin intoxication are the kidney and the brain. A worldwide awareness is needed for thousands of people who are exposed to this new phenylalanine‐like neur...

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autono...

The caudomedial nidopallium (NCM) is a telencephalic area involved in auditory processing and memorization in songbirds, but the synaptic mechanisms associated with auditory processing in NCM are largely unknown. To identify potential changes in synaptic transmission induced by auditory stimulation in NCM, we used a slice preparation for path-clamp...

Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nu...

What are the cellular mechanisms underlying memory and learning? This question has puzzled scientists and philosophers from Aristotelis, who proposed the hypothesis that the heart is the site of learning (Aristotle 350 B.C.E), to John Locke and his wax tablet analogy (Locke 1689), to contemporary ideas regarding synaptic plasticity (Bliss and Lomo...

The glomus cells in the carotid bodies (CB) detect alterations in pH and pCO₂ and low pO₂ level in arterial blood. The carotid sinus nerve conveys the information related to the oxygen level to 2nd-order neurons in the nucleus tractus solitarius (NTS) via tractus solitarius (TS), which is part of the chemoreflex pathways. It has been demonstrated t...

The peripheral chemoreflex activation by hypoxia produces autonomic and respiratory adjustments. The NTS is the primary site of peripheral chemoreceptor afferents in the CNS and RVLM‐projecting NTS neurons are related to the sympathoexcitatory component of this reflex. In a previous study we demonstrated that ATP modulates the spontaneous and evoke...

The cNTS is the site of synaptic relay of peripheral chemoreceptor afferents and ventral medulla‐projecting NTS neurons are related to respiratory and autonomic responses to chemoreflex. It has been suggested that ATP and L‐glutamate are co‐transmitters in the NTS and NO can modulate glutamatergic and purinergic effects in the brain. Here, we evalu...

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during...

Peripheral chemoreflex activation in awake rats or in the working heart-brainstem preparation (WHBP) produces sympathoexcitation, bradycardia and an increase in the frequency of phrenic nerve activity. Our focus is the neurotransmission of the sympathoexcitatory component of the chemoreflex within the nucleus of the tractus solitarius (NTS), and re...

The role of GABA in the central processing of complex auditory signals is not fully understood. We have studied the involvement of GABA A-mediated inhibition in the processing of birdsong, a learned vocal communication signal requiring intact hearing for its development and maintenance. We focused on caudomedial nidopallium (NCM), an area analogous...

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrit...

Nuclear actin and nuclear myosins have been implicated in the regulation of gene expression in vertebrate cells. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. In this study, myosin-Va, phosphorylated on a conserved serine in the tail domain (...

Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure. Both CB1 and CB2 cannabinoid receptors have been described in the nucleus tractus solitarius (NTS), which receives direct afferent projections of cardiovascular reflexes. In the present study we evaluated the effects of WIN 55212-2 (WIN),...

CIH induces several changes in the cardiovascular system including hypertension. Previous experiments from our laboratory showed that juvenile rats exposed to CIH presented hypertension and an increased sympathoexcitatory response to chemoreflex activation. In the present study we evaluated possible changes in synaptic transmission in NTS neurons o...

Because urethane is a widely used anesthetic in animal experimentation, in the present study, we evaluated its effects on neurons of the nucleus of the solitary tract (NTS) in brain stem slices from young rats (25-30 days old). Using the whole cell configuration of the patch-clamp technique, spontaneous postsynaptic currents (sPSCs) and evoked exci...

Na+ channel recovery from inactivation limits the maximal rate of neuronal firing. However, the properties of presynaptic Na+ channels are not well established because of the small size of most CNS boutons. Here we study the Na+ currents of the rat calyx of Held terminal and compare them with those of postsynaptic cells. We find that presynaptic Na...

Birdsong is a learned vocal behaviour that requires intact hearing for its development in juveniles and for its maintenance during adulthood. However, the functional organization of the brain circuits involved in the perceptual processing of song has remained obscure. Here we provide evidence that GABAergic mechanisms are an important component of...

A glutamate-sensitive inward current (Iglu) is described in rat cerebellar granule neurons and related to a glutamate transport mechanism. We examined the features of Iglu using the patch-clamp technique. In steady-state conditions the Iglu measured 8.14 1.9 pA. Iglu was identified as a voltage-dependent inward current showing a strong rectificatio...

Bursts of neuronal activity are transmitted more effectively as synapses mature. However, the mechanisms that control synaptic efficiency during development are poorly understood. Here, we study postnatal changes in synaptic ultrastructure and exocytosis in a calyx-type nerve terminal. Vesicle pool size, exocytotic efficiency (amount of exocytosis...

The mammalian auditory brain stem receives profuse adrenergic innervation, whose function is poorly understood. Here we investigate, during postnatal development, the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large glutamatergic EPSC, evoked by...

The mammalian auditory brain stem receives profuse adrenergic innervation, whose function is poorly understood. Here we investigate, during postnatal development, the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large glutamatergic EPSC, evoked by...

We have investigated the effect of ω-PnTx3-3 (referred to in previous papers simply as Tx3-3), a peptide toxin from the venom of the spider Phoneutria nigriventer, on neuronal high-voltage activated (HVA) Ca2+ channels, using whole-cell patch-clamp. ω-PnTx3-3 (120 nM) blocked 74±8% of the total HVA Ca2+ currents of cerebellar granule neurones, with...

Recent studies have demonstrated that granule cells in rat cerebellar slices exhibit a tonic form of GABAergic inhibition. The presence of a similar constitutive GABAergic conductance was investigated in synaptically coupled cultures of neonatal rat cerebellum. In cells exhibiting spontaneous inhibitory postsynaptic currents (IPSCs), application of...