Biology subjects

Ceballos, C. C.

Publications and source records attributed to Ceballos, C. C..

7 recordsLinked to original sources

bioRxiv2025

Axo-Axonic Synapses on Descending Neurons in the Drosophila Ventral Nerve Cord

Axo-axonic synapses can veto, amplify, or synchronize spikes, yet their circuit-scale logic is unknown. Using the complete electron-microscopy connectome of the adult male Drosophila, we charted every axo-axonic input onto the 1,314 descending neurons that carry brain commands to the ventral nerve cord. By definition, any synapse connected to a descending neuron within the cord is axo-axonic. Thus, we uncovered the ascending-descending and interneurons-descending axo-axonic relationship. Neurons with many partners (high-degree) integrate into the network without clustering into an interconnected rich-club of hubs. We identified an octet of ascending neurons (AN08B098) whose axo-axonic input to the Giant Fibers (DNp01) predicted modulation of the escape circuit. Immunostaining confirms their cholinergic identity, while optogenetic activation confirmed that this excitatory cohort increases DNp01 excitability, validating connectome-derived rules. Our work delivers a map of axo-axonic wiring in a complete ventral nerve cord connectome and provides constraints for models of fast motor control.

neuroscience↗

bioRxiv2024

Dendritic synaptic integration modes under in vivo-like states

The neural code remains undiscovered and understanding synaptic input integration under in vivo-like conditions is just the initial step toward unraveling it. Synaptic signals generate fast dendritic spikes through two main modes of temporal summation: coincidence detection and integration. In coincidence detection, dendrites fire only when multiple incoming signals arrive in rapid succession, whereas integration involves summation of postsynaptic potentials over longer periods with minimal membrane leakage. This process is influenced by ionic properties, especially as the membrane potential approaches the firing threshold, where inactivating currents play a critical role. However, the modulation of temporal summation by these currents under in vivo-like conditions has not been thoroughly studied. In our research, we used computer simulations of a single dendritic branch to investigate how three inactivating currents -- A-type potassium, T-type calcium, and transient sodium -- affect temporal summation. We found that calcium and sodium currents promote integrative behavior in dendrites, while potassium currents enhance their ability to act as coincidence detectors. By adjusting the levels of these currents in dendrites, neurons can flexibly switch between integration and coincidence detection modes, providing them with a versatile mechanism for complex tasks like multiplexing. This flexibility could be key to understanding how neural circuits process information in real time. SignificanceNeurons consist of specialized structures that shape computation. The soma processes inputs from dendrites and communicates via its axon. Dendrites have a branched architecture. They receive excitatory signals and generate dendritic spikes. These spikes allow individual branches to convert inputs into spiking patterns prior to somatic integration. Depending on input synchrony, branches operate as coincidence detectors or integrators, which is determined by ionic currents. Our study explores how these currents affect signal summation. We found that potassium currents favor coincidence detection, while calcium and sodium currents promote integration. Cellular mechanisms finely tune these currents, enabling dendrites to adjust processing modes in response to synaptic inputs.

neuroscience↗

bioRxiv2024

Prevalent co-release of glutamate and GABA throughout the mouse brain

Several neuronal populations in the brain transmit both the excitatory and inhibitory neurotransmitters, glutamate, and GABA, to downstream neurons. However, it remains largely unknown whether these opposing neurotransmitters are co-released onto the same postsynaptic neuron simultaneously or are independently transmitted at different time and locations (called co-transmission). Here, using whole-cell patch-clamp recording on acute mouse brain slices, we observed biphasic miniature postsynaptic currents, i.e., minis with time-locked excitatory and inhibitory currents, in striatal spiny projection neurons (SPNs). This observation cannot be explained by accidental coincidence of monophasic miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively), arguing for the co-release of glutamate and GABA. Interestingly, these biphasic minis could either be an mEPSC leading an mIPSC or vice versa. Although dopaminergic axons release both glutamate and GABA in the striatum, deletion of dopamine neurons did not eliminate biphasic minis, indicating that the co-release originates from another neuronal type. Importantly, we found that both types of biphasic minis were detected in other neuronal subtypes in the striatum as well as in nine out of ten additionally tested brain regions. Our results suggest that co-release of glutamate and GABA is a prevalent mode of neurotransmission in the brain.

neuroscience↗

bioRxiv2021

Highly sensitive genetically-encoded sensors for population and subcellular imaging of cAMP in vivo

Cyclic adenosine monophosphate (cAMP) integrates information from diverse G protein-coupled receptors, such as neuromodulator receptors, to regulate pivotal biological processes in a cellular- and subcellular-specific manner. However, in vivo cellular-resolution imaging of cAMP dynamics in neurons has not been demonstrated. Here, we screen existing genetically-encoded cAMP sensors, and further develop the best performer to derive three improved variants, called cAMPFIREs. These sensors exhibit up to ten-fold increased sensitivity to cAMP and a corrected, cytosolic distribution. cAMPFIREs are compatible with both ratiometric and fluorescence lifetime imaging, and can detect cAMP dynamics elicited by norepinephrine at physiologically-relevant, nanomolar concentrations. Imaging of cAMPFIREs in awake mice reveals tonic levels of cAMP in cortical neurons that are associated with wakefulness, and are differentially regulated in different subcellular compartments. Furthermore, enforced locomotion elicits neuron-specific, bidirectional cAMP dynamics, in part, mediated by norepinephrine. Finally, cAMPFIREs also function in Drosophila, suggesting that they have broad applicability for studying intracellular signaling in vivo.

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↗

bioRxiv2018

Reimplementation of the Potjans-Diesmann cortical microcircuit model: from NEST to Brian

1This work targets the replicability of computational models to provide the community with tested and proven open-source models to be used in new studies and implementations. The Potjans-Diesmann model describes a cortical microcircuit containing two cell types (excitatory and inhibitory) distributed in four layers, and represents the cortical network below a surface of 1 mm2. The original implementation of the Potjans-Diesmann model was based on the NEST simulator and our goal here was to re-implement the model in the Brian 2 simulator and obtain the same results presented in the reference article. We did not replicate analyses that involve changes in the network structure. Our replicated network model presents activity dynamic patterns very similar to the ones observed in the original model, with comparisons made in terms of firing rates and synchrony and irregularity measures. In conclusion, the Potjans-Diesmann model was successfully replicated in a different platform than the one in which it was originally implemented.

systems biology↗