127 research outputs found
Editorial: Insights in cellular neurophysiology: 2022
No full textThis Research Topic invited Frontiers Editors to highlight significant challenges and recent accomplishments in the neuroscientific field and highlight future directions. Seven contributions were gathered, including original articles, a review, and a methods report
Editorial for This Special Issue "Synaptic Transmission: From Molecular to Neural Network Levels"
No full textWe invited contributions reporting new evidence of synaptic mechanisms and their network-level impacts for this Special Issue. The six research articles published in this collection, from 33 authors, cover many aspects of synaptic function and plasticity, from single-cell mechanisms to neuronal network properties. These papers elucidate the physiological and pathological conditions underlying synaptic transmission, giving new perspectives for future applications and therapies
Dopaminergic Modulation of Prefrontal Cortex Inhibition
No full textThe prefrontal cortex is the highest stage of integration in the mammalian brain. Its functions vary greatly, from working memory to decision-making, and are primarily related to higher cognitive functions. This explains the considerable effort devoted to investigating this area, revealing the complex molecular, cellular, and network organization, and the essential role of various regulatory controls. In particular, the dopaminergic modulation and the impact of local interneurons activity are critical for prefrontal cortex functioning, controlling the excitatory/inhibitory balance and the overall network processing. Though often studied separately, the dopaminergic and GABAergic systems are deeply intertwined in influencing prefrontal network processing. This mini review will focus on the dopaminergic modulation of GABAergic inhibition, which plays a significant role in shaping prefrontal cortex activity
The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models
No full textAutism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that include a variety of forms and clinical phenotypes. This heterogeneity complicates the clinical and experimental approaches to ASD etiology and pathophysiology. To date, a unifying theory of these diseases is still missing. Nevertheless, the intense work of researchers and clinicians in the last decades has identified some ASD hallmarks and the primary brain areas involved. Not surprisingly, the areas that are part of the so-called "social brain", and those strictly connected to them, were found to be crucial, such as the prefrontal cortex, amygdala, hippocampus, limbic system, and dopaminergic pathways. With the recent acknowledgment of the cerebellar contribution to cognitive functions and the social brain, its involvement in ASD has become unmistakable, though its extent is still to be elucidated. In most cases, significant advances were made possible by recent technological developments in structural/functional assessment of the human brain and by using mouse models of ASD. Mouse models are an invaluable tool to get insights into the molecular and cellular counterparts of the disease, acting on the specific genetic background generating ASD-like phenotype. Given the multifaceted nature of ASD and related studies, it is often difficult to navigate the literature and limit the huge content to specific questions. This review fulfills the need for an organized, clear, and state-of-the-art perspective on cerebellar involvement in ASD, from its connections to the social brain areas (which are the primary sites of ASD impairments) to the use of monogenic mouse models
Regulation of output spike patterns by phasic inhibition in cerebellar granule cells
No full textThe complex interplay of multiple molecular mechanisms taking part to synaptic integration is hard to disentangle experimentally. Therefore, we developed a biologically realistic computational model based on the rich set of data characterizing the cerebellar glomerulus microcircuit. A specific issue was to determine the relative role of phasic and tonic inhibition in dynamically regulating granule cell firing, which has not been clarified yet. The model comprised the excitatory mossy fiber-granule cell and the inhibitory Golgi cell-granule cell synapses and accounted for vesicular release processes, neurotransmitter diffusion and activation of different receptor subtypes. Phasic inhibition was based on stochastic GABA release and spillover causing activation of two major classes of postsynaptic receptors, alpha 1 and alpha 6, while tonic inhibition was based on steady regulation of a Cl- leakage. The glomerular microcircuit model was validated against experimental responses to mossy fiber bursts while metabotropic receptors were blocked. Simulations showed that phasic inhibition controlled the number of spikes during burst transmission but predicted that it specifically controlled time-related parameters (firing initiation and conclusion and first spike precision) when the relative phase of excitation and inhibition was changed. In all conditions, the overall impact of alpha 6 was larger than that of alpha 1 subunit-containing receptors. However, al receptors controlled granule cell responses in a narrow +/- 10 ms band while alpha 6 receptors showed broader +/- 50 ms tuning. Tonic inhibition biased these effects without changing their nature substantially. These simulations imply that phasic inhibitory mechanisms can dynamically regulate output spike patterns, as well as calcium influx and NMDA currents, at the mossy fiber-granule cell relay of cerebellum without the intervention of tonic inhibitio
Integration and regulation of glomerular inhibition in the cerebellar granular layer circuit
No full textInhibitory synapses can be organized in different ways and be regulated by a multitude of mechanisms. One of the best known examples is provided by the inhibitory synapses formed by Golgi cells onto granule cells in the cerebellar glomeruli. These synapses are GABAergic and inhibit granule cells through two main mechanisms, phasic and tonic. The former is based on vesicular neurotransmitter release, the latter on the establishment of tonic gamma-aminobutyric acid (GABA) levels determined by spillover and regulation of GABA uptake. The mechanisms of post-synaptic integration have been clarified to a considerable extent and have been shown to differentially involve alpha 1 and alpha 6 subunit-containing GABA-A receptors. Here, after reviewing the basic mechanisms of GABAergic transmission in the cerebellar glomeruli, we examine how inhibition controls signal transfer at the mossy fiber-granule cell relay. First of all, we consider how vesicular release impacts on signal timing and how tonic GABA levels control neurotransmission gain. Then, we analyze the integration of these inhibitory mechanisms within the granular layer network. Interestingly, it turns out that glomerular inhibition is just one element in a large integrated signaling system controlled at various levels by metabotropic receptors. GABA-B receptor activation by ambient GABA regulates glutamate release from mossy fibers through a pre-synaptic cross-talk mechanisms, GABA release through pre-synaptic auto-receptors, and granule cell input resistance through post-synaptic receptor activation and inhibition of a K inward-rectifier current. Metabotropic glutamate receptors (mGluRs) control GABA release from Golgi cell terminals and Golgi cell input resistance and autorhythmic firing. This complex set of mechanisms implements both homeostatic and winner-take-all processes, providing the basis for fine-tuning inhibitory neurotransmission and for optimizing signal transfer through the cerebellar corte
Anisotropy and Frequency Dependence of Signal Propagation in the Cerebellar Circuit Revealed by High-Density Multielectrode Array Recordings
No full text: The cerebellum is one of the most connected structures of the central nervous system and receives inputs over an extended frequency range. Nevertheless, the frequency dependence of cerebellar cortical processing remains elusive. In this work, we characterized cerebellar cortex responsiveness to mossy fibers activation at different frequencies and reconstructed the spread of activity in the sagittal and coronal planes of acute mouse cerebellar slices using a high-throughput high-density multielectrode array (HD-MEA). The enhanced spatiotemporal resolution of HD-MEA revealed the frequency dependence and spatial anisotropy of cerebellar activation. Mossy fiber inputs reached the Purkinje cell layer even at the lowest frequencies, but the efficiency of transmission increased at higher frequencies. These properties, which are likely to descend from the topographic organization of local inhibition, intrinsic electroresponsiveness, and short-term synaptic plasticity, are critical elements that have to be taken into consideration to define the computational properties of the cerebellar cortex and its pathological alterations
Editorial: Distributed networks: new outlooks on cerebellar function, volume II
No full textSince the original launch of this Research Topic in 2013, much progress has been made in our understanding of cerebellar contributions beyond the sensorimotor realm. Overwhelming evidence now indicates that the cerebellum is involved in a diverse range of behavioral processes such as decision making, spatial navigation and emotional control. Indeed, it can be argued that the cerebellum is likely involved in all types of behavior, ranging from the control of involuntary reflexes to higher order problem solving.
This second volume brings together findings from the animal, theoretical and clinical fields and includes 18 articles involving 74 authors that explore the latest evidence of cerebellar contributions to motor and non-motor functions (Figure 1). Cerebellar contributions are considered in terms of brain wide networks, information processing, and the clinical consequences that arise when these circuits are disrupted
- …
