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Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood. This review begins with a brief survey of cerebellar topography. Next, it reviews the development of stripes in the cerebellum with a particular emphasis on the embryological origins of cerebellar interneurons. These data serve as a foundation to discuss the hypothesis that cerebellar compartment boundaries also restrict cerebellar interneurons, both excitatory [granule cells, unipolar brush cells (UBCs)] and inhibitory (e.g., Golgi cells, basket cells). Finally, it is proposed that the same PC scaffold that restricts afferent terminal fields to stripes may also act to organize cerebellar interneurons.

A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release. The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons. However, these electrical signals cannot cross the synapses between neurons. Instead, the information is carried across the synapse by molecules called neurotransmitters. Calcium ions control the release of neurotransmitters. There is a high concentration of calcium ions outside the neuron but they are not able to pass through the cell membrane under normal conditions. However, when an electrical impulse reaches the synapse, ion channels in the membrane open and allow calcium ions to enter the cell. Once inside, the ions activate the release of neurotransmitters by binding to proteins called release sensors. Several experiments on the release of neurotransmitters have studied the synapses between neurons and muscle fibers. These studies found that the higher the concentration of ions outside the neuron, the higher the rate at which the neurotransmitters were released. However, the timing of release—the length of time over which the neurotransmitters were released—did not depend on the concentration of calcium ions. Arai and Jonas have now studied neurotransmitter release at a synapse in a region of the brain called the cerebellum. These experiments also found that the timing of the release did not depend on the ion concentration, suggesting that this may be a general property of neurotransmitter release. To find out more, Arai and Jonas created a mathematical model of neurotransmitter release. This model suggests that for the timing of release to remain the same, the ion channel and the release sensor must be located close together in the presynaptic terminal. If they are not close together, the timing of release becomes blurred and more dependent on the external calcium concentration. Further experiments confirm the prediction of the model by showing that the calcium channels and the release sensors in these synapses are very close together. The next challenge will be to find out whether the conclusions are also valid for other synapses where the calcium channels and release sensors are further apart.

Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.

Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas. Using independent analyses of light and electron microscopy data from mouse neocortex, we show that a surprisingly large fraction of cortical myelin (half the myelin in layer 2/3 and a quarter in layer 4) ensheathes axons of inhibitory neurons, specifically of parvalbumin-positive basket cells. This myelin differs significantly from that of excitatory axons in distribution and protein composition. Myelin on inhibitory axons is unlikely to meaningfully hasten the arrival of spikes at their pre-synaptic terminals, due to the patchy distribution and short path-lengths observed. Our results thus highlight the need for exploring alternative roles for myelin in neocortical circuits. The brain is far away from the muscles that it controls. In humans, for example, the brain must be able to trigger the contraction of muscles that are more than a meter away. This task falls to specialized motor neurons that stretch from the brain to the spinal cord, and from the spinal cord to the muscles. Neurons transmit information (in the form of electrical nerve impulses) along their length through cable-like structures called axons. The axons of the motor neurons are so long that, if they were ‘naked’, it would take at least a second for nerve impulses to travel their entire length. Such a long delay between thoughts and actions would make rapid movement impossible. Nerve impulses are able to travel from the brain to the muscles much more quickly, because they are wrapped with a substance called myelin that acts like electrical insulation. Myelin helps the nerve impulses travel up to 100 times faster down the axon. Not surprisingly, diseases that damage myelin, such as multiple sclerosis, severely disrupt movement and sensation. Not all of the brain’s myelin is found around the long axons of motor neurons. The outer layer of the brain, known as the cerebral cortex, also contains myelin. However, most neurons within the cerebral cortex are only a few millimeters long. So what exactly is myelin doing there? Micheva et al. have now used electron microscopy and light microscopy to study the neurons in the cortex of the mouse brain. This revealed that up to half of the myelin in some layers of the cortex surrounds the axons of inhibitory neurons (which reduce the activity of the neurons they signal to). Moreover, one particular subtype of inhibitory neuron accounts for most of the myelinated inhibitory axons, namely inhibitory neurons that contain a protein called parvalbumin. Exactly why parvalbumin-containing neurons are myelinated remains a mystery. Myelin covers only short segments of the axons of these neurons, so it would speed up the transmission of signals by less than a millisecond – probably not enough to make a meaningful difference. Parvalbumin-containing neurons often signal frequently, and thus require large amounts of energy. One possibility therefore is that myelin helps to meet these energy requirements or to reduce energy consumption. Further research will be needed to test this and other ideas.

Dendrites of fast-spiking basket cells (FS BCs) impact neural circuit functions in brain with both supralinear and sublinear integration strategies. Diverse spatial synaptic inputs and active properties of dendrites lead to distinct neuronal firing patterns. How the FS BCs with this bi-modal dendritic integration respond to different spatial dispersion of synaptic inputs remains unclear. In this study, we construct a multi-compartmental model of FS BC and analyze neuronal firings following simulated synaptic protocols from fully clustered to fully dispersed. Under these stimulation protocols, we find that supralinear dendrites dominate somatic firing of FS BC, while the preference for dispersing is due to sublinear dendrites. Moreover, we find that dendritic diameter and Ca 2+ -permeable AMPA conductance play an important role in it, while A-type K + channel and NMDA conductance have little effect. The obtained results may give some implications for understanding dendritic computation.

Abstract The underlying biology of essential tremor (ET) is poorly understood. Purkinje cell (PC) loss has been observed in some studies, although this finding remains somewhat controversial. Basket cells are interneurons whose axonal collaterals form a plexus around PC soma. When there is PC loss, this basket plexus appears empty. We used dual immunohistochemical staining for calbindin D28k and glutamic acid decarboxylase to quantify \"empty baskets\" as an indirect and alternative method of detecting PC loss. Microscopic analyses on 127 brains included ET and a spectrum of motor neurodegenerative diseases (50 ET, 27 spinocerebellar ataxias [SCAs], 25 Parkinson disease, 25 controls). The median percentage of empty baskets in ET patients was 1.5 times higher than controls (48.8% vs 33.5%, p < 0.001) but lower in ET than in SCA1 (59.7%, p = 0.011), SCA2 (77.5%, p = 0.003), and SCA6 (87.0%, p < 0.001). PC loss is not a feature of SCA3, and the median percentage of empty baskets (30.1%) was similar to controls (p = 0.303). These data provide support for PC loss in ET and are consistent with the notion that ET could represent a mild form of cerebellar degeneration with an intermediate degree of PC loss.

Neurons receive synaptic inputs with diverse temporal patterns in vivo, and their integration of these patterns is critical for understanding information processing mechanisms in the brain. Fast-spiking basket cells, which perform both supralinear and sublinear dendritic integration, are essential for inhibitory control in the hippocampus. However, their responses and the mechanisms underlying different temporal input patterns remain unclear. To address this question, we apply inputs with varying windows of time to a detailed compartmental model of basket cells. Our results reveal that when synaptic inputs are randomly dispersed, temporal integration in FS BCs exhibits a sigmoid-like response within the temporal window. In contrast, synchronous input protocols more effectively elicit action potentials, while asynchronous inputs generate more spikes in response to suprathreshold stimuli. Further analysis shows that the supralinear dendrites of fast-spiking basket cells primarily mediate this nonlinearity to asynchronous inputs, owing to their larger dendritic diameters. Moreover, we discover that delayed rectifier channels reduce sensitivity to synchronous inputs, whereas N-type channels enhance sensitivity to asynchronous inputs. These results provide insights into the mechanisms underlying the temporal coding of fast-spiking basket cells, which is crucial for understanding their role in neuronal oscillations.

Basket cells (BC) are inhibitory interneurons of the cerebellar molecular layer (ML) forming peri-somatic synapses on Purkinje cells (PC). BC physiological and computational properties remained poorly understood and not clearly differentiated from those of stellate cells (SC). We identified BCs in acute mouse cerebellar slices and measured their intrinsic excitability and synaptic responsiveness. BCs and SCs were similar in some respects, although BCs showed stronger and faster synaptic excitation in response to parallel fibre (pf) bursts. The analysis of BC inhibition of PCs was extended over a broad parameter space using accurate multi-compartmental computational models. During pf bursts, the BC reduced the PC response at low-frequency, while SCs did it at high-frequency. BC filtering was explained by the engagement of HCN1 channels, which activated slowly during low-frequency BC-PC GABAergic transmission. The increase of input conductance caused by HCN1 channels in the PC soma, by shunting excitatory currents elicited by pfs and travelling toward the axon initial segment (AIS), reduced the PC output frequency. These simulations predict that BC and SC operate in tandem, setting the frequency band of PC transmission through the regulation of PC frequency/response curves.